Muscle contraction begins with a signal from your brain, which propagates through your nervous system and causes the release of the neurotransmitter acetylcholine at the neuromuscular junction. When the acetylcholine binds to its receptors a muscle, a series of intracellular events occurs and the muscle fibers contract. The energy source for this contraction is called ATP. During normal exercise, glucose (sugar) and oxygen produce a sufficient amount of ATP to fuel muscle contractions (via the Krebs Cycle). However, during extreme efforts like sprinting, our bodies require more energy and a different energy cycle is revved up to produce much greater volumes of ATP for a short amount of time. Each of these cycles of energy production produces pyruvic acid, a product of glucose breakdown. At moderate levels of exercise, moderate levels of pyruvic acid are produced and much of it goes into the Krebs Cycle to produce energy; at high levels of exercise, high levels of pyruvic acid are produced.

Pyruvic acid is converted into lactic acid and at high levels of exercise, more pyruvic acid is produced than the body can handle and a buildup of lactic acid results. At a certain point, our body can clear lactic acid at the same rate that it is being made. This is called the lactate threshold and it is a very important aspect of training for elite athletes. The higher their lactate threshold, the longer they can go at a high tempo before the build-up of lactic acid brings on burning and muscle fatigue.

A process called the lactate shuttle is important because it allows for some of the lactic acid to be oxidized and converted into additional energy for the muscles. Efficient clearance of lactate is likely an important factor in lactate threshold and it has been suggested that lactate may ultimately contribute to the prevention of fatigue.

The burning sensation associated with the build-up of lactic acid is due to the presence of hydrogen ions in the blood. The hydrogen ions released by the lactic acid may act locally to indicate fatigue, but may also act on peripheral nervous system receptors to send the signal to the brain that glucose is being utilized at a high rate and muscle fatigue is setting in. In this way, the central nervous system (which initiated the muscle contraction in the first place) regulates the physical activity.

Vitamin D is found in foods such as fatty fishes, eggs, beef liver, and UV light-exposed mushrooms. So….why is it that people head out into the sun and say, “I need to go and get some vitamin D?”

It is because UVB exposure above the UV index level of 3 is necessary to activate the vitamin D. There are several forms, or vitamers, of vitamin D and they are not all equal. The foods mentioned above contain a pro-form (7-dehydrocholesterol) that becomes active (cholecalciferol) in the skin following UV exposure. The cholecalciferol then travels from the skin to the liver, where it is hydroxylated (calcifediol/25-hydroxyvitamin D3). Finally, the modified vitamin moves to the kidney, where it undergoes another round of hydroxylation to become calcitriol (1,25-dihydroxyvitamin D3), the most active form of vitamin D3. The vitamer of vitamin D that is supplemented in foods is cholecalciferol- it has already been irradiated and is therefore active.

It is possible to ingest too much vitamin D, which makes sense since its role is to maintain normal blood calcium levels. Too much vitamin D results in hypercalcaemia, a condition that can lead to increased blood pressure, weight loss, nausea, vomiting, and even kidney damage. For pregnant women, hypercalcaemia can cause very serious fetal damage. Excessive vitamin D levels occur when people take too many supplements- not from getting too much sun exposure.

Here are the details….digestive enzymes break down ingested asparagus and produce methanethiol (or methyl mercaptan), which is believed to be the aromatic culprit in stinky asparagus urine. (However, some scientists believe that a different family of thioesters that are the byproducts of acid reacting with sulfur-containing alcohol are responsible.) The methanethiol waste product is then (somewhat mysteriously) transmitted through the kidney to the urine. Ironically, asparagus is a diuretic, which contributes to the rapidity with which the scented urine exits the body. The aromatic nature of the methanethiol is due to the fact that it is released as a gas when you urinate.

Interestingly, a similar process is employed by skunks when they make their musk. The difference with skunks is that they have specific glands for storing and concentrating sulfur-containing chemicals, which they can create from more products than asparagus. Methanethiol is also released from decaying organic matter. It is truly a wonderful aroma.

There has been some controversy as to whether everyone has stinky urine after eating asparagus. I am aware of no recent, controlled clinical study on this topic, but there is an alternative hypothesis. It is quite possible that, while we all conduct this digestive process, we do not all have smell receptors that are sensitive tor methanethiol. We all have a very unique array of olfactory receptors and it turns out that the ability to smell asparagus is a dominant genetic trait and is therefore not universal. We are born with about 400 olfactory receptors out of a possible 1000. This does not mean that we can only smell 400 different aromas; a single odorant binds with varying affinities to different olfactory receptors, creating a distinct pattern of nerve impulses to the brain that define the scent. Another odorant may bind similar olfactory receptors with different affinities, creating a unique pattern of nerve impulses to the brain and a completely unique sensory representation. The brain then interprets that scent and associates it with the object. We can smell thousands of different smells, based on the unique combination of smell receptors rendered active by a particular odorant.

Our olfactory systems are a very primitive part of our brain and tightly linked with the hippocampus and our memories. This is why certain smells evoke strong memories. Perhaps you can conduct a controlled trial of the genetic patterns of methanethiol sensing in your family at the next family gathering. That will certainly create some smell-associated memories!

The more traditional IUD is made of copper, while a newer iteration of the IUD is made of plastic and has a small compartment in it that is filled with a derivative of the hormone progesterone. This type of IUD is sometimes referred to as an intrauterine system (IUS). An IUD/IUS is T-shaped and about the size of a quarter; it is placed inside the uterus by a doctor or nurse. (The average uterus is the size of a clenched fist.) They are recognized as a form of “long-acting reversible contraception” because they can be left in the uterus and prevent pregnancy for 5-10 years. An IUD/IUS is one of the most cost efficient and effective types of contraception available [1]. They are the most common form of birth control in the world (45% of married women in China use it), although they are used by only about 1% of women United States. Americans tend to use birth control pills more than IUDs/IUSs.

The IUD and IUS are similar in size and shape and both devices cause a low-grade local inflammatory response that makes the uterine environment less hospitable to sperm or a fertilized egg. The IUD and IUS have additional mechanisms for preventing pregnancy that are unique. Copper ions released from the IUD enhance the inflammatory response and the presence of the copper ions is toxic to sperm. It is like a spermicide. In addition, the mucous in the uterus can become thicker, making it more difficult for sperm to make their way up to an egg. Finally, the copper-laden fluids of the uterus make the environment hostile to an embryo should an egg become fertilized.

The IUS, on the other hand, functions more like conventional contraceptive methods because it constantly releases levonorgestrel, a progesterone derivative. The constant level of progesterone prevents the uterine wall from becoming full of nutrients and thereby inhibits implantation. As with birth control pills, an IUS maintains a non-pregnant hormonal state so that the body cannot foster an embryo. Over time, there is some glandular atrophy and ovulation is prevented. Once it is removed, however, most women have no trouble getting pregnant if they want to.

[1] Mavranezouli I, Wilkinson C, Glasier A. The cost-effectiveness of long-acting reversible contraceptive methods in the UK: analysis based on a decision-analytic model developed for a National Institute for Health and Clinical Excellence (NICE) clinical practice guideline. Hum Reprod. 2008;23(6):1338-1345.

Hair can be considered in two separate sections, the root and the shaft. The hair root is located inside of the follicle and exists below the portion of the skin while the shaft is the portion of hair that extends out from the skin. The root of the hair receives nutrients from the blood through the dermal papilla. The nutrients that are supplied to the root of the hair through the dermal papilla, combined with oil from the sebaceous gland, can contribute to hair’s strength. This strength of the hair shaft can contribute to how long it grows before it breaks. Also, keeping it from drying out can prevent it from breaking. As such, a dry environment or treating hair with a lot of chemicals can limit its length.

The hair that grows out of the hair follicle can be course or fine. Coarse hair is thicker because it has a thick central core of cells (called the medulla) that make it stronger and less likely to break due to environmental factors. This is a genetic trait and blonde or fine hair often lacks this dense core. It is thus easier for someone with thick (likely dark) hair to grow it very long. Although the average rate of hair growth is apparently half an inch per month, the rate at which hair grows is also genetically determined.

Hair also sheds, naturally. The normal cycle of a hair follicle lasts from 2-8 years. The first phase, also called anagen, is when the hair shaft grows out of the root. The second phase in the cycle is called catagen and is the period during which the hair follicle shrinks and the root detaches from the blood supply. Catagen lasts for a couple of weeks. The final phase, telogen, is when the hair does not grow, but is still attached. This phase lasts for several weeks. After telogen, the hair follicle moves back into anagen and begins to grow a new hair. It is the pushing out of the old hair that leads to shedding. A normal rate of shedding is 50-100 hairs a day. It is thus the length of this cycle that partially determines how long a hair can get. If one has inherited a shorter hair growth cycle of 2 years, and hair grows at an saverage of half an inch a month, the longest it could grow if it were strong is 12 inches. However, if someone had a very long hair growth cycle of 8 years and their hair were strong, it could grow 4 feet or more!

Super-long hair thus occurs only when there is a combination of several factors: a decent rate of growth, coarse hair, a non-drying environment, a long hair follicle shedding cycle, and, of course, the choice to not visit a barber.

Your dog can actually eat a little bit of chocolate, but if they eat about an ounce of milk chocolate per kilogram of body weight or as little as a couple of mouthfuls of cocoa mulch, there will be trouble. At that quantity, dogs may experience seizures. These effects are due to the caffeine and theobromine that are in chocolate. In the case of chocolate, the theobromine is more of a factor. Theobromine (which is also called xantheose) is a water soluble alkaloid that is metabolized in the liver. The byproducts of its metabolism are methylxanthine and then methyluric acid. Theobromine blocks the breakdown of cyclic AMP, thus acting as a stimulant through a mechanism much like caffeine. In humans, theobromine has less of an impact on the central nervous system than does caffeine and may also be responsible for the aphrodisiac qualities attributed to chocolate.

In dogs, however, theobromine is metabolized much more slowly than in humans, prolonging its effects on the central nervous system and smooth muscle. The first symptoms experienced by animals with theobromine poisoning may be a result of vagal nerve blockade and include increased of heart rate as well as disruption of the smooth muscles in the digestive tract. Later on, dogs can suffer from seizures due to loss of vagal nerve activity and the stimulatory effects of accumulated cyclic AMP. These symptoms can lead to death in serious cases, although early treatment is usually successful.

Interestingly, cats would also suffer from the negative effects of theobromine poisoning, but they do not have sweet taste receptors and are rarely drawn to ingest chocolate.

This nicotinic acetylcholine receptor (nAChR) is endogenously activated by acetylcholine, but is also highly responsive to the drug nicotine. When activated by either acetylcholine or nicotine, the ligand-gated nAChR opens and elicits an immediate response from the effector cells. Cells that have nAChR are found throughout the body, particularly at neuromuscular junctions and in the brain. The immediate effect of nicotine on the cholinergic system is actually a release of epinephrine (which is also known as adrenaline) and a speeding up of the heart. That sensation, however, rapidly subsides and the tobacco user then experiences a state of calm. In addition to activating the body’s cholinergic system, nicotine blocks the release of insulin from the pancreas and causes a brief period of elevated blood sugar and suppressed appetite. Because nAChRs can become less sensitive to the effects of nicotine, repeated use makes the body less responsive to the same dose and people who use nicotine need to use more to get the same effects. In addition, withdrawal from nicotine makes the user feel edgy and agitated, often leading to chain use in order to avoid these negative feelings.

The peripheral effects of nicotine may cause some of the feelings of physical relaxation, but it is the effects on the brain that are responsible for its addictive properties. When nicotine activates nAChrs in the brain, it causes the release of dopamine, the neurotransmitter associated with feelings of comfort and well-being. This pathway of dopamine release has also been called the “reward system” and is activated similarly, but to a greater degree, with other drugs such as cocaine, amphetamines, and alcohol. In addition, the reward system responds to pleasurable activities such as having sex, eating food, or receiving a lot of money. Activation of the reward system involves dopamine release from an area of the brain called the nucleus accumbens and activation of D2 dopamine receptors at target brain regions, resulting in inhibition of cAMP in these target brain regions. With continual stimulation, the reward system becomes more sensitive to the drug, reinforces behaviors of that drug’s use, and motivates the individual to seek out situations in which the drug is available. This combination of factors is what makes addiction especially difficult to combat.

Caffeine functions similarly to nicotine in that it activates the reward system and also binds to a receptor designed for neurotransmitters; in particular, it binds to adeonsine receptors. In the case of caffeine, however, it blocks the adenosine receptors and prevents adenosine from acting on the receptor rather than stimulating the receptor. By blocking the adenosine pathways, caffeine prevents adenosine from calming neural systems and results in arousal. The specifics of these mechanisms have yet to be completely defined, but one place where adenosine has an effect is on dopamine cells. The disinhibition of dopamine cells will prolong their effect and this may be one reason why caffeine makes nicotine more rewarding.

A second mechanism that might play a role in the increased reward experienced by an individual drinking coffee and smoking a cigarette at the same time has to do with the second known mechanism of caffeine. It has a more global effect of altering the metabolic processes of cells throughout the body. Caffeine allows for build up of intracellular energy stores (ATP) by blocking the enzymes that usually breaking them down. This effect is similar to that imparted upon cells by epinephrine, the neurohormone responsible for arousal. Epinephrine is released initially when nicotine is used and the use of caffeine with nicotine may prolong the state of alertness and focus that is experienced in the initial phase of nicotine use.

Ironically, smoking can actually decrease the length of time that caffeine is effective. However, the use of both nicotine and caffeine at the same time initiates an intense feeling of alertness that may help people feel more awake in the mornings. In addition, the use of both drugs together can powerfully activate the brain’s reward system. The reward system will therefore crave continued activation to that degree and other parts of the brain will associate those feelings of well-being with the taste, smell, and situational aspects of nicotine and caffeine consumed with one another, further perpetuating their concomitant use.

1. National Institute of Drug Addiction, National Institutes of Health statistics. Available at: http://www.nida.nih.gov/ResearchReports/Nicotine/nicotine2.html#impact. Accessed: November 29, 2008.

So, they compromised after many lively debates on the topic and now we all have an 8-minute snooze session. As a scientist, I wanted to determine the neurological basis for keeping a person on the fine line that separates sleep from wakefulness. It turns out, however, that the true basis for the 8 (to 9) minute snooze lies within the clock’s mechanics. Classic alarm clocks are built on a three bit counter that refreshes at the start of the ninth minute. The snooze button taps into this moment to reset itself. Newer digital clocks, however, allow for all different snooze settings. I have reviewed some basic sleep principles for you to consider in the case that you have the luxury of setting your own snooze duration (and actually want to get up).

That magical morning moment when sleep becomes wakefulness requires that many physiological systems line up. When we sleep, our brains cycle through five different stages of sleep that have been defined as stages 1-4 and rapid eye movement (REM) sleep. Stages 1 and 2 are lighter levels of sleep while 3 and 4 are deep sleep (also known as delta sleep). REM is the sleep period during which our brain is the most active, creating dreams. This may also be the most important part of sleep for learning and memory. We move in and out of REM sleep several times during the night and end up spending approximately 20% of our sleep time in REM sleep; when we are awoken during an REM sleep cycle, we often remember our dreams. As we approach morning, our sleep cycles are shorter and the time spent in stage 1, stage 2, and REM sleep increases.

When our alarm goes off in the morning, our body has been preparing for wakefulness by altering its temperature and hormonal milieu. Our brains move out of stage 1 or REM sleep to shut off our alarm. If we turn it off all the way, we may have a bout of sleep-induced amnesia that causes us to forget the brief moment of wakefulness. However, if we have a snooze button that keeps us from moving fully back into stage 1, we can slowly wake up and keep the new day in our consciousness. I am, however, unaware of any scientific publications that define a specific physiological or neurological event that occurs at 8 minutes after waking.

As one final note, it is recommended that adults get seven to nine hours of sleep a night and many factors including insomnia, sleep deprivation, napping patterns, and lifestyle- can alter normal sleep cycles and make it harder to get up in the morning and you may need to adjust your snooze schedule accordingly.

Figure can be accessed at: http://helpguide.org/life/sleeping.htm. September 29, 2008.

The reason is that bacteria thrive in moist environments like those created with sweat and cotton socks. With the right environment, the bacteria feast on the dead skin cells from your feet and produce stinky waste products.

It has recently been discovered that common foot odors are likely caused by Staphylococcus epidermis, a normal resident of the foot (Ara K, et al). One of the byproducts released by Staphylococcus epidermis as it degrades the leucine in sweat is isovaleric acid, or 3-methylbutanoic acid, and this is what causes the stink that is present in your sneakers and in locker rooms. Ironically, isovaleric acid releases volatile esters that are often used in perfumes. It is strange to think that stinky shoes and fine fragrances are so closely related. Although we can discern the difference between stinky isovaleric acid and its ester fumes, we all smell isovaleric acid to different degrees. According one recent set of genetic analyses, one person may be 10,000 times more sensitive to the sweaty stink of isovaleric acid than others (Menashe I, et al)!

More severe bacterial conditions of the foot are caused by Micrococcus sedentarius, or Kytococcus sedentarius, and sufferers of this infection are often left with severe skin damage and the stink from their feet is due to the production of thiols, sulfides, and thioesters, which contain sulfur (English JC, et al).

Preventing these bacteria from taking over your feet is as simple as keeping your feet clean and aired out. So, wash up those dogs and walk around barefoot a bit. Because isovaleric acid is not very water soluble, it is necessary to use some sort of soap to get the stink off your feet when washing them. Once your feet are clean a little bit of citral, citronella, or geraniol can inhibit the production of isovaleric acid (Ara K, et al). As far as remedying the sneakers, try putting them in the freezer for 24 hours (after placing them in a plastic bag, perhaps…). That should kill of some of the bacteria that have taken up residence.

 
English JC. Pitted Keratolyis. WebMD; August 30, 2006. Available at: http://www.emedicine.com/derm/TOPIC332.HTM. Accessed September 12, 2008.

Ara K, Hama M, Akiba S, et al. Foot odor due to microbial metabolism and its control. Can J Microbiol. 2006;52(4):357-364.

Menashe I, Abaffy T, Hasin Y, et al. (2007) Genetic Elucidation of Human Hyperosmia to Isovaleric Acid. PLoS Biology. 2007;5(11):e284.

Activation of the sympathetic nervous system and the resultant release of epinephrine is responsible for physiological reactions in addition to increased heart rate. These other responses also help the body prepare to react and include dilation of the pupils to increase visual acuity, the breakdown of liver glycogen so that glucose is readily available to fuel muscles, enhanced lung function, hypervigilance, and the redirection of blood flow from central organs to the muscles. During this time, the parasympathetic nervous system, the part of the central nervous system that is responsible for digestion, reproduction, and energy storage, is shut down. The body is focused on survival and the activities of the sympathetic nervous system.

From day to day, our brains primarily utilize glucose as fuel. Glucose is a simple sugar that is the most convenient form of fuel for cells. Although the brain is only two percent of the body’s total weight, it consumes an average of 70 percent of the body’s glucose, which comes as no surprise because we have up to 100 billion energy-hungry neurons in our brains. Glucose, a simple sugar, is absorbed by brain cells directly from the blood stream. Glycogen, a larger carbohydrate, can be broken down by the liver and kidney to release more glucose into the bloodstream if necessary. The body continually adapts its metabolism to ensure that plenty of glucose is available for the brain. During times of extreme stress, blood flow is decreased to muscles and other organs that also consume glucose to ensure that the brain has a continuous supply of glucose.

The second way to address this question is from a longterm perspective. As we age, our brains must protect themselves from free radicals that are generated during normal cellular metabolic processes. During stressful times, our bodies are exposed to greater loads of free radicals. Throughout our lives, brain cells can be damaged by free radicals. It is thus important to consume foods with antioxidants because antioxidants protect brain cells from free radicals. One food that is especially high in antioxidants is blueberries. It has been demonstrated that diets high in blueberries may assist in rapid recovery from severe oxidative brain injury (Stromberg I, et al.), may reverse age-related cognitive decline (Lau FC, et al.), and help with memory (Andres-Lacueva C, et al.). Other fruits high in polypheonls, the specific antioxidant component in blueberries, are kiwis, plums, cherries, blackberries, currants and apples.

Stromberg I, et al. Neurol. 2005 Dec;196(2):298-307.

Lau FC, et al. Neurobiol Aging. 2005 Dec;26 Suppl 1:128-32.

Andres-Lacueva C, et al. Natr Neurosci. 2005 Apr;8(2):111-120.

Pullman, Washington

When there is a topic of great interest, several groups will often design experiments to learn more about that topic. These decisions are made simultaneously and it can take several years for the results from these studies to be reported. When designing experiments, researchers must take several factors into account. Among these might be: the group of people who will be tested, the duration of the experiment, the outcome that is to be measured, and how that outcome will be measured. As one might imagine, the choices made in each of these categories have the potential to affect the final conclusions of the study. For example, one experiment might test how a high fat diet affects the waistline of middle-aged women over five years while another study might test a high fat diet on sleep quality in adolescent boys over one week. These two studies could be interpreted quite differently and different conclusions regarding high fat diets might be reported.

One real life scenario in which confusing results have been reported is in the consumption of coffee. Coffee has been blamed for transient increases blood pressure (Childs E and de Wit H) and increased cholesterol (Higdon JV and Frei B). Other experiments, however, have shown that female lifelong coffee drinkers perform better on cognitive tests late in life (Johnson-Kozlow M, et al.). Finally, recent studies have shown that coffee may be a valuable source of antioxidants (Halvorsen BL, et al.) and folic acid (Child Health Alert) and might even prevent certain diseases (Higdon JV and Frei B). This plethora of results is clearly confusing, but if the different experimental questions and designs are taken into account, it is understandable how these different results came to be. Coffee has many different aspects (caffeine, antioxidants, processing chemicals) that could be used as the basis of experimental questions. The populations of individuals tested in these examples range from general populations of caffeine and non-caffeine users to aged women and pregnant women. The experimental time frame ranged anywhere from one day to a lifetime. The outcomes were measured by surveys, blood tests, laboratory tests and clinical tests of cognition. Each study provides unique information, but the results might seem contradictory when synopsized into a headlines. If you are curious, read more about the details of the study to understand the context of the results. And, with coffee, the real take-home message is what we have heard many times before: anything is okay within moderation.

Child Health Alert. 2007 Mar;25:5-6.

Childs E and de Wit H. Psychopharmacology (Berl). 2006 May;185(4):514-523.

Halvorsen BL, et al. Am J Clin Nutr. 2006 Jul;84(1):95-15.

Higdon JV and Frei B. Crit Rev Food Sci Nutr. 2006;46(2):101-123.

Johnson-Kozlow M, et al. Am J Epidemiol. 2002 Nov 1;156(9):842-850.