A Literal "Beer Gut"

Imagine you are a police officer and suddenly the car in front of you is beginning to drive erratically. You dismiss it at first, thinking the driver was just momentarily distracted. Then he starts swerving left and right, slowing down and then speeding up. You take a closer look inside the car. Looks like a family of four. Presumably the wife in the passenger seat, two kids in the back. The kids are behaving. He's not using his phone. The driver doesn't look distracted.

After the man nearly runs the car up on the sidewalk, you flash your lights. He pulls over without incident and appears cooperative, almost happy. Carefree, in fact.

"What's the problem, officer?" His words are slurred, virtually confirming your suspicion. This guy is three sheets to the wind (incidentally, that is an old maritime phase referring to when fasteners holding the sails became loose and control of the boat was lost).

"Have you been drinking tonight, sir?"

"Nope! Just had some spaghetti and breadsticks. Hey, I like your badge. Shiny! Can I hold your gun?" He becomes giddy with laughter.

You look over at the woman in the passenger seat. "It's true, officer. He never drinks! He gets this way after having pasta sometimes. I told him not to have seconds. How about I drive instead and we just forget the whole thing?"

Sounds like a family trying to put one over on the police, but there really is a condition called "auto-brewery syndrome" or "gut fermentation syndrome". People experience this rare condition when microbes turn the belly into a brewery. 

People with the rare condition known as "auto-brewery syndrome" can turn this carbohydrate-rich plate of pasta into enough alcohol to make them feel drunk.

A woman recently diagnosed with the syndrome had her DUI charges dismissed. She was monitored for a twelve hour period, taking a breathalyzer test every few hours. Despite having no alcohol whatsoever, her blood alcohol content rose steadily throughout the day, reaching to four times the legal limit by the end of the period.

As we've mentioned in previous articles, our body is home to trillions of microbes that collectively made up our microbiome. These microbes are largely intestinal bacteria and fungi. They perform indispensable tasks for us, such as helping to produce neurotransmitters, vitamins, and immune regulators. But on very rare occasions, certain yeasts in our gut, namely Saccharomyces cerevisiae or Candida albicans, can grow out of control and start converting carbohydrates into alcohol.

People with auto-brewery syndrome quite literally have a "beer gut". The yeast in their body can produce alcohol without the person taking a sip of booze. Some people learn to adapt and live with this higher-than-average blood alcohol content, much like anyone who builds up a tolerance to alcohol by increasing hepatic (liver) metabolism. Unbeknownst to them, some people have been living with the condition for years.

People with auto-brewery syndrome actually make alcohol in their intestines where the fungi live. So feeding them hops and tapping their stomach is not going to provide you and your friends with a ready source of free beer.

It is not known why the yeast can take such a foothold in the gut of these patients. One documented case report suggests that a course of antibiotics, which wipe out a lot of "friendly" gut bacteria but don't hurt yeast, can create an environment in the intestine that favors growth of the yeast. With the bacteria depleted, there is less competition for nutrients, so the yeast can grow out of control. Some researchers have argued that overgrowth of fungi is not to blame, but rather the patient may have genetic defects that prevent the liver from metabolizing the minute, normal levels of alcohol that may ferment in the gut. These two possibilities are not mutually exclusive.

Yeast are a type of fungi that have enzymes able to convert sugars like glucose into pyruvate, ethanol (alcohol), and carbon dioxide as waste products. One organism's waste is another organism's treasure!

In addition to creating obvious hazards and embarrassing situations, auto-brewery syndrome causes bad hangovers as well. Is there any way to alleviate this problem? One report stated that a 10 week course of anti-fungal drugs and probiotics, the latter of which aim to replenish the gut with bacteria that belong there, eliminated the condition from the patient.

So if you see someone acting like a belligerent fool for no logical reason...well, most likely they're just being a jerk. But there is a small chance that they have auto-brewery syndrome and deserve your compassion rather than condemnation.

Contributed by:  Bill Sullivan
Follow Bill on Twitter.

Cordell, B., & McCarthy, J. (2013). A Case Study of Gut Fermentation Syndrome (Auto-Brewery) with Saccharomyces cerevisiae as the Causative Organism International Journal of Clinical Medicine, 04 (07), 309-312 DOI: 10.4236/ijcm.2013.47054 

In Winter, Frozen Isn't Just A Disney Movie

Winter came early to a huge portion of the United States in 2014. Cold temperatures, slick roads and wind were the found in many places in mid-November. Heck, parts of Buffalo disappeared for more than a weekend.

Frozen is based on a Hans Christian Andersen tale called

The Snow Queen, written in 1844. In Andersen’s story,

there is an evil mirror that only reflects the bad in

something, none of the good. That’s like this post – we

talk about how winter cold can harm, not how it can

bring two sisters together and heal a broken kingdom.

It’s the cold temperatures that are the source of so much misery. A storm in the North Pacific changed the flow of the jet stream, and freezing temperatures dipped low into the US. People had to take measures to avoid freezing to death – literally.

Low temperatures can kill a person in a couple of ways. Frostbite is the freezing of parts of the body. Your cells are mostly water; when water freezes it forms crystals. The crystals are sharp and are larger than the same amount of water (ie. water expands when it freezes). This leads to punctures in the cell membranes; the affected parts of the body sort of digest themselves due to the release of enzymes from the broken cells.

Frostbite usually affects the extremities - toes, fingers, nose, ear lobes, private parts for men - because they have less blood flow and are harder to keep warm. Your body also sacrifices these body parts in an effort to keep warm by constricting blood vessels to keep the majority of blood from cooling and carrying the cold back to the center of the body.

Reduced blood flow is usually the reason for frostbite; less blood in the area means less heat, which means a greater risk for freezing. The reduction could come from physiologic vasoconstriction, or from underlying medical conditions that result in poor circulation. For instance, people with diabetes have poorer circulation and are much more susceptible to frostbite.

We add salt to the streets to lower the freezing temperature

of water. But on your skin, salt and ice lead to rapid frostbite.

The first person to try the salt and ice challenge could be

forgiven, but for anyone who has seen the videos of the

aftermath and still tried it – I have no sympathy for you.

Areas that undergo frostbite can sometimes be saved by the  infiltration of new blood vessels (angiogenesis) and the replacing of the dead cells. But if freezing of deeper tissues (muscles, tendons, bones) has occurred, this will probably not be possible. If larger/deeper areas are involved or if there is infection, amputation could be necessary. If no treatment is rendered – a person could actually die from the toxins released by an infection or from the dead tissue.

Interestingly, many sources of frostbite information state that if you are going out into the cold, you shouldn’t drink alcohol or smoke (tobacco or marijuana), as they can predispose you to frostbite. A 1997 study of blood flow in acute smoking showed that peripheral blood circulation was decreased from the moment smoking began. A 2008 study extended this to second hand smoke as well, showing that nicotine impairs microvascular function.

Marijuana gets a double hit, since it lowers blood pressure AND vasoconstricts the peripheral vessels. This is bad news for Colorado; legal pot and lots of cold weather. Likewise, drinking alcohol immediately before going out in the cold is dangerous because it is vasoconstrictive immediately after ingestion.

There’s a potential new problem in frostbite. With the

increase in solid organ transplants, it is becoming more

evident that some organs are being transported at too

low a temperature and they are being damaged. A recent

study examined frostbite in a liver to be transplanted

into an 18 month old.

On the other hand, the same cold temperatures that lead to frostbite can also kill you directly. Hypothermia is the bone-chilling cold you feel when your entire body’s temperature is dropping. Your normal body temperature is 98.6 ˚F (37 ˚C) or thereabouts. At 95 ˚F (35 ˚C) hypothermia begins. At 91 ˚F (32.7 ˚C) you get amnesia, and below 85 ˚F (29.5 ˚C) you lose consciousness. Now you’re in trouble.

Hypothermia can kill you in several ways, two of which have to do with electricity. Your heart beats because it supplies itself with a chemico-electrical jolt every second or so. This is what occurs in the sinus and AV nodes of the heart and is based on an electrical charge difference across the cells' membranes in the node.

Low body temperature messes with the membrane potential, so the heartbeat is slow and erratic. Too slow (bradycardia) or too erratic (arrhythmia) leads to a heartbeat so dysfunctional that it won’t push the blood through your body and you die from cardiac failure.

Electrical messaging is also how your central and peripheral nervous systems work. Not only does cold temperature slow the nerve impulse by altering the membrane potential, but it also slows the transfer of the signal from one neuron to the next. The neural synapse is the gap between two or more neurons and relies on chemical messages (neurotransmitters) released from the upstream neuron to trigger and electrical signal in the downstream neurons.

Cold temperature slows the release and/or reuptake of the chemicals in the synapse, so brain function is altered. This explains the confusion many people experience in hypothermia and the “paradoxical undressing” that victims often carry out.

That’s right, people who are so cold as to affect their brain activity often strip right there in the cold. It seems that as the small muscles that control vasoconstriction in an effort to prevent hypothermia will finally fail after working for a long time.

In some cases, lowering the body’s temperature radically is

beneficial. Originally called therapeutic hypothermia, the

technique is now more controlled and is called target

temperature management, as reviewed in this late 2014

publication. Lowering the body’s temperature for a short time

is effective in preventing some of the damage done by

cardiac arrest or stroke.

This creates a short vasodilation that brings a burst of relative warm blood to the skin. The victim may feel a hot flash, and in his/her altered neurologic state might take their clothes off to cool down. I saw no fewer than 16 cases based on just a cursory literature search.

Finally,  our proteins have evolved to function best when they are held at 98.6 ˚F. One could ask, did the protein conformation (its folded shape) evolve because of our temperature, or did our temperature evolve because our proteins fold a certain way? In either case, every protein’s function is based on its conformation, and the folding and shape are dependent somewhat on temperature.

Lower your body’s temperature and the proteins’ shapes will change. When this happens they don’t work so well, and this throws off your entire physiology and metabolism. Throw it off too far, and there’s no coming back.

Next time we talk together - what can a person do to avoid frostbite and hypothermic death? Stay out of the cold by moving to Florida or buy every warm piece of clothing North Face offers. These are ways humans overcome the environment, but there are also physiologic ways our bodies can combat the cold.

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




Palmers PJ, Hiltrop N, Ameloot K, Timmermans P, Ferdinande B, Sinnaeve P, Nieuwendijk R, & Malbrain ML (2014). From therapeutic hypothermia towards targeted temperature management: a decade of evolution. Anaesthesiology intensive therapy PMID: 25421924
 
Argacha, J., Adamopoulos, D., Gujic, M., Fontaine, D., Amyai, N., Berkenboom, G., & van de Borne, P. (2008). Acute Effects of Passive Smoking on Peripheral Vascular Function Hypertension, 51 (6), 1506-1511 DOI: 10.1161/HYPERTENSIONAHA.107.104059
 
Adams MD, Earnhardt JT, Dewey WL, & Harris LS (1976). Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat. The Journal of pharmacology and experimental therapeutics, 196 (3), 649-56 PMID: 4606
 

Morioka C, Kondo H, Akashi K, Matsumura K, Ochi N, Makinaga G, & Furukawa T (1997). The continuous and simultaneous blood flow velocity measurement of four cerebral vessels and a peripheral vessel during cigarette smoking. Psychopharmacology, 131 (3), 220-9 PMID: 9203232

 

The Friday Five

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

1. The mystery behind Death Valley's 'Wandering Stones' appears to have finally been solved. For decades scientists have debated why hundreds of rocks move across Racetrack Playa, leaving trails behind them. Read this and/or watch the video below to see how this happens.

2. We’ve recently covered some of the things that alcohol does to your brain in this post. Here is a short video that not only addresses the question, “Does alcohol kill brain cells?”, but also explains where this notion originated. Cheers!

3. Now that we know what alcohol does, how about coffee? What does coffee do to the brain? AsapSCIENCE is here to explain in this short video.

4. Economist Richard Reeves uses Legos to demonstrate the chances of upward mobility in America.

5. Richard Feynman’s famous lectures are now available for free here. Go learn some physics from the master who had a knack for making complex principles understandable and entertaining.

Science quote of the week:

“Science is the great antidote to the poison of enthusiasm and superstition.” –Adam Smith

Contributed by:  Bill Sullivan

Follow Bill on Twitter: @wjsullivan

Norris, R., Norris, J., Lorenz, R., Ray, J., & Jackson, B. (2014). Sliding Rocks on Racetrack Playa, Death Valley National Park: First Observation of Rocks in Motion PLoS ONE, 9 (8) DOI: 10.1371/journal.pone.0105948

State Fairs and Stiff Beers: Why We Can't Stop Drinking

Recently, the Indiana State Fair served its first alcoholic beverage since 1946. With the popularity of local breweries and wineries on the rise in Indiana – nearly a hundred of each in the Hoosier State – a reversal of the near-70 year alcohol drought at the State Fair seemed inevitable.

The logo for the Beer and Wine Exhibit 2014 at the Indiana State Fair

Meanwhile, in Indiana and beyond, many scientists are buzzing about trying to understand exactly what alcohol does to our brain. From time to time, researchers lace a rodent’s drinking water with varying amounts of ethanol in order to observe how this impacts their zig-zagging through mazes. Despite consuming alcohol for millennia, we remain remarkably ill-informed regarding how alcohol affects the nervous system. Why do we consume alcohol? How does it affect us neurologically in the short-term, and why do we keep going back for more? The answers are complex, but we are beginning to see them without beer goggles.

Going back at least to 8,000 B.C., the pages of history are splashed with examples of alcohol usage, the reasons ranging from medicinal (analgesic and antiseptic), religious (Communion wine), aesthetic (perfumes and cosmetics), preservative (safeguarding of food), industrial (fossil fuels), financial (barter) and recreational (drinking in times of merriment and sorrow to alter one’s mood).  The mighty powers behind constructing the Pyramids of Giza rationed payments for their laborers in measures of beer. The Middle Ages and well beyond saw numerous reports of alcohol (primarily beer) being safer to drink than water - until the Germ Theory of Disease helped make two parts of hydrogen and one part oxygen safe to imbibe. The Royal Navy of the United Kingdom received a daily rum ration until the 1970s, when someone of importance finally became worried that operating heavy machinery might be precarious while under the influence.

Many, then, are the uses of alcohol, and diverse are instances of its enduring consumption, inherent in legions of cultures for thousands of years. For all the other ways in which the world has changed, in some ways the consumption of alcohol seems little different today. As in ancient and medieval times, we drink to please others and we drink to please ourselves.

While the liver is the key organ that metabolizes alcohol, the majority of the effects we feel after having thrown back a few (or a few too many, depending on the occasion) are primarily neurological. It is important to understand that alcohol is more than simply a depressant. Alcohol is a complex drug that causes variable effects based on the amount ingested. It affects a variety of neurological pathways and targets different structures in the brain, resulting in a cocktail of symptoms not easily explained by a single molecular alteration. After minutes of ingestion, alcohol enters the blood stream and readily crosses the blood-brain barrier, typically a highly selective barrier between the circulating blood and brain fluid, and acts on a number of receptors both directly and indirectly. Even moderate alcohol consumption can have adverse effects on sleep patterns and temperature regulation, which is controlled by a small almond-shaped structure located just above the brainstem known as the hypothalamus. While a nightcap may help you feel drowsy, larger quantities of alcohol affect REM sleep, causing restlessness and wakefulness through the course of the night.

Those who have had too much are afflicted with cerebellar defects, such as difficulty walking and impaired motor coordination. Alcohol can also do a number on the cerebral cortex, which is responsible for judgment, cognition, planning, and social interaction. Some reports suggest that alcohol can bind up to 100 independent receptors in the brain, and the various locations of these processes in the cranium determine the specific changes in behavior. Other symptoms associated with drinking include changes in memory and emotion, slurred speech, and blackouts. Small to moderate quantities of alcohol have also been reported to decrease brain volume. 

Low and moderate alcohol users show a decrease in adjusted brain volume based on magnetic resonance imaging results in the Framingham Offspring Study cohort (Paul et al. JAMA Neurology 2008)

Alcohol also alters the release of numerous neuro-transmitters and neuropeptides, which are chemical messengers and protein-like molecules, respectively, involved in transmitting signals in the brain. For example, alcohol decreases the release of glutamate, the key excitatory neurotransmitter in the brain, while increasing the amount of GABA, an inhibitory neurotransmitter, potentially resulting in a slowdown of brain function. All these consequences seem negative, but there’s a catch:  booze increases the production of dopamine in the “reward center” of the brain. This creates a positive feedback loop, making us want more and more of this elixir.

A number of different structures in the brain are affected by the consumption of alcohol. In particular, the ‘pleasure center’ is responsible for the effects of the dopamine reward pathway and the limbic system can lead to changes in memory and emotion

Indeed, there are a number of reasons why libations are such a central part of our life. Here’s a small excerpt. First and foremost, we like it! This pleasure can be explained neurologically by the activation of the dopamine-reward pathway, socially by the fact that it is an event that often brings people together (be it in times of merriment or sorrow), and psychologically by how it is a low risk/high reward activity and relieves stress, helping one cope with emotional turmoil. 

If viewed from an evolutionary perspective, moderate alcohol consumption hardly affects fitness: Although the Porter in Shakespeare’s Macbeth says that drink “provokes the desire but takes away the performance,” science tells us that alcohol can bolster both. So spirits, unlike the painful fear of heights, seem no powerful threat to either survival or procreation. Additionally, the “drunken monkey” hypothesis put forth by Dr. Robert Dudley suggests that we drink because we associate alcohol with a nutritional reward, as our anthropoid ancestors primarily subsisted on ripe fruits that contained low levels of ethanol. Since moderate and chronic alcoholism are associated with a number of vitamin deficiencies, such as folate, vitamin B12, vitamin A, and calcium, I have difficulty believing that alcohol consumption is, in fact, an evolutionary hangover, but this argument has been made from time to time. However, as with most things in life, consuming alcohol in moderation can maximize its positive effects while minimizing the risk associated with consumption.

So as you weave your way to the Grand Hall to the Beer and Wine exhibition at the State Fair, right after having scarfed down your deep-fried Twinkie and a few shucks of corn, if you down that beer (or three, the limit imposed at the State Fair this year), it won’t be because you have to. You’ll swill that brew because you want to.

Contributed by:  Aarti Chawla

Follow Aarti on Twitter

National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov/

Diamond I, & Messing RO (1994). Neurologic effects of alcoholism. The Western journal of medicine, 161 (3), 279-87 PMID: 7975567

Németh Z, Kuntsche E, Urbán R, Farkas J, & Demetrovics Z (2011). Why do festival goers drink? Assessment of drinking motives using the DMQ-R SF in a recreational setting. Drug and alcohol review, 30 (1), 40-6 PMID: 21219496

Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, Decarli C, & Wolf PA (2008). Association of alcohol consumption with brain volume in the Framingham study. Archives of neurology, 65 (10), 1363-7 PMID: 18852353

The DNA of The Price of Darkness

If you could study the DNA of anyone on Earth to learn what made him or her tick, who would you choose? Noam Chomsky, Bill Gates, Serena Williams, Madonna? It is probably safe to say that not many people would have chosen Ozzy Osbourne, the founder of the heavy metal pioneers, Black Sabbath. But scientists couldn’t wait to put Ozzy under the microscope…and for good reason.



I only have black genes!

Also known as The Prince of Darkness, Ozzy is a remarkable human specimen. It is no secret that he has constantly struggled with addiction, toured for nearly half a century, bit off the head of a bat, survived reality television, and, on top of all that, has kids. His wife and manager, Sharon, once compared his resilience to that of a cockroach. Ah, love and marriage.

What powerful forces were finally able to put the Prince of Darkness in his place? Wife and kids.

When scientists sequence a genome, they basically get to read the DNA of that organism, which is analogous to learning the ingredients of a recipe. In heavy metal parlance, Ozzy’s genome is the biological version of “Diary of a Madman”. Doctors, and even Ozzy himself, have long been bewildered at his continued existence…most people who climb aboard a crazy train and live the Ozzy lifestyle would have been dead long ago!

Ozzy once considered that he was like a cat with nine lives, but there were no feline genes detected in his genome. In fact, like most scientific results, more questions were raised than answered. Among some of the more intriguing things spotted in his DNA was a never-before-seen mutation in his ADH4 gene. ADH4 encodes a protein called alcohol dehydrogenase 4 that processes alcohol and has been linked to alcohol and drug dependence. However, we need to learn a lot more about ADH4 and other metabolic genes if we are to make sense of the results.

Researchers also found traces of Neanderthal genes in Ozzy’s DNA. However, this probably has nothing to do with his wild life or ability to howl all night long since a large number of people also possess Neanderthal DNA. Recent research indicates that ~20% of the Neanderthal genome still exists in modern humans of non-African ancestry.

So what does all of this tell us and should we be knocking on Bob Dylan’s door for a DNA sample? Frankly, the data is just a ‘Blizzard of Ozz’ at the moment. There is no “Ozzy Osbourne” gene, nor anything concrete that explains why he is who he is. There is nothing that will be of immediate benefit to substance abusers or help Justin Bieber write better songs. We still have a lot to learn about the complexities of gene expression regulation. For example, you can’t make a cake if you only know the ingredients. We need to know how and when those ingredients are used and in what proportions. Similarly, we can’t understand Ozzy Osbourne just from a list of his genes.

Genes are kind of like different musical instruments, but other factors that are “epigenetic” in nature (epigenetic meaning “above the gene”) control the level of each instrument, tell it when to play, or when to rest. Scientists are discovering that many factors from our environment can influence epigenetic factors, which in turn regulate the amount of a gene’s activity. Nevertheless, Ozzy’s genome has provided some clues into what genes we might want to explore further, and that kind of knowledge is power. The more genomes that are sequenced, the more confidence we can have in the correlations that arise between gene and phenotype.

For more, check out this TEDMED talk where the Ozzman and Sharon discuss his genome.

You can also read more about Ozzy’s genome results, and his hilarious medical advice (which has greater credibility than that discharged by another “Dr. Oz” we know!), in his book, “Trust Me, I’m Dr. Ozzy”.

Contributed by: Bill Sullivan

Follow Bill on Twitter: @wjsullivan

Sankararaman, S., Mallick, S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N., & Reich, D. (2014). The genomic landscape of Neanderthal ancestry in present-day humans Nature, 507 (7492), 354-357 DOI: 10.1038/nature12961

Luo X, Kranzler HR, Zuo L, Lappalainen J, Yang BZ, & Gelernter J (2006). ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 31 (5), 1085-95 PMID: 16237392