Christmas food for thought: the gains and pains of laughter

As Christmas approaches like a freight train I, like many, scramble to buy last minute gifts and prepare myself to gorge on feasts and booze and laughter(?) – all part of a joyous(??) family gathering. In last effort to procrastinate until the very end, I present to you this short series of posts on various and totally random holiday-related themes. Enjoy!

Sings: Petri dish sterilizing near an open fire, lab rats nipping on my shoe, data woes cried by grad students, and PIs dressed like You-Know-Who! Ok, this might’ve gotten a laugh out of grad students. Anyone? I’ll show myself out.

Laughter permeates holiday gatherings. Dubbed “grooming at a distance”, laughter is thought to establish and maintain bonds between individual primates of all sorts. Like yawning, the mere sound of laughter often triggers giggling fits in others in a contagion-like manner. Within four-tenths of a second after exposure, electrical activity spreads out through areas involved in cognition, emotion, sensation and movement; this triggers facial contortions, spasmodic breathing and bodily convulsions as we involuntarily emit a series of curious vocalizations, ready to infect another.

Collapsing in a quivering heap, we are left under-the-influence of a deluge of a neuroendocrine cocktail. The amount of epinerphrine, a hormone in the fight-or-flight response plummets, while dopac, a major metabolite of dopamine, shoots up. Laughter also triggers the release of pain-relieving endorphins and growth- and metabolism-boosting growth hormone, which together with other chemicals form somewhat of a panacea for the mind and body. As Robert Burton once astutely wrote in 1621, “Mirth…prorogues life, whets the wit, makes the body young, lively and fit for any manner of employment.”

So where’s the evidence?

British Medical Journal produced a snicker-inducing, tongue-in-cheek report that synthesized findings from 785 papers on the health benefits of laughter. To round things up, they threw in harmful effects for good measure, while discarding papers written by authors with “Laugh” in their last name which where nonetheless “not particularly amusing”. Here’s what they found.

In terms of the psyche, laughter increased tolerance to pain in the lab, but hospital clowns did not reduce distress in children going through minor surgery to any observable extent. Humorous movies had minimal success on serious mental illnesses like schizophrenia, and group-based humor therapy did not particularly benefit late-onset depression in Alzheimer’s disease, though there was some improvement in patient morale and mood. Laughter was associated with life-long satisfaction, but there’s no evidence that one causes the other either way.

More mirthful news comes from laughter’s effect on the body. A 20min funny movie acutely reduced the stiffness of blood vessels and made them more limbre. A sense of humour lowers your risk of heart attack and improved lung function in those with chronic obstructive pulmonary disease, an illness that makes it difficult to breathe. In the latter case the credit goes to hospital clowns, whom apparently until the year of study (2008) were still regarded by some brave souls as non-terrifying entities.

Laughter had no consistent effects on immune functions such as natural killer cells, but sometimes aided the surgical removal of a pouch of pus by bursting it through laughter-generated muscle contractions. Laughter also benefits metabolism: compared to a monotonous lecture that drooled forever on, a comedy show helped control blood sugar levels after a meal. A 15min-bout of genuine laughter burns up to 40 calories, so battling the average 6000-calorie Christmas dinner would requires 37.5hrs of merriment to burn off. Better get those jokes ready.

Finally, if you’re trying to get pregnant through in vitro fertilization (test-tube baby), perhaps consider hiring a clown dressed like a chef de cuisine. In one study, such a clown entertained 110 would-be mothers after embryo transfer for 12-15 minutes with saucy jokes and magic tricks, “a recipe of success” that led to ~16% increase in pregnancy rate compared to the 109 non-clowned controls, adding another win for medicinal clowning.

Unfortunately laughter is not without its pains. Laughter weakens resolve and promotes your preference for certain brands, so keep a skeptic eye on that joke-cracking salesman. A hearty guffaw can cause temporary loss of consciousness, perhaps due to the sudden increase in pressure in the chest cavity that triggers a neural response. Laughing can screw up the electrical activity in the heart causing it to pump irregularly, to the point of cardiac arrest or rupture, giving “dying of laughter” a more sinister undertone.

Laughter can lead to abnormal collection of gas between the lung and chest wall or engorgement of air sacs of the lungs, resulting in labored breathing. The sharp intake of air to initiate laughter can promote inhaling foreign objects, causing you to choke on a small piece of turkey, while frequent exhaling disseminates infection. Laughter may also wreck havoc on your alimentary canal, dislocating the jaw or puncturing the esophagus (your “food-tube”), so maybe eat first and laugh later. You might also want a clear line to the wash(bath)room. Laughter can cause incontinence stemming from involuntary contractions of bladder muscles, which surprisingly may be counteracted by Ritalin.

And finally, uproarious laughter may not be so funny to your brain. Cataplexy, a condition where a person suddenly looses muscle tone, can be triggered by laughter and other salient stimuli, leaving you unceremoniously collapsed under the Christmas tree. That is, unless only one side of you is affected. In one documented case, laughter triggered cataplexy only on the right side of a patient’s body, leaving her presumably capable of continuing laughing on the left side of her face.

Laughter and other pleasurable things may precipitate headaches in the unfortunate, sometimes due to sacs of jello-like material in the third ventricle, a fluid-filled compartment in the brain. Laughter may also be no laughing matter to people with patent foramen ovale (PFO), whom have a hole in the heart that should’ve closed after birth but didn’t. Take this case for example: after 3 minutes of roaring laughter, a PFO patient lost her words (literally) and had a stroke.

This report from BJM obviously shows that laughter is not all beneficial, but it overall carries a low risk of harm in the general population. In terms of cost-benefit analysis a good laugh is still beneficial. Yet, as always, more research calls. As the authors put it:

“It remains to be seen whether, for example, sick jokes make you ill, if dry wit causes dehydration, or jokes in bad taste cause dysgeusia (note: distortion of the sense of taste), and whether our views on comedians stand up to further scrutiny.”
R E Ferner, & J K Aronson (2013). Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis BJM DOI: 10.1136/bmj.f7274


#SfN13 Stressed out mice turn to carbs for comfort food

Poster ZZ3 Ghrelin protects against stress by promoting the consumption of carbohydrates.T. Rodrigues. Z. Patterson. A. Abizaid. Carleton University, Ottawa, ON, Canada

In this world nothing can be said to be certain, except death and taxes.– Benjamin Franklin

Personally, I’d add stress to that.

There’s no question that chronic stress is a killer. Handled badly, stress can lead to anxiety, memory impairments, cardiovascular disease and sleep disorders. We all have our own strategies for coping with stress, some healthier than others. Me? I turn to food.


Cavities galore or stress relief? Source: 

Apparently, so do bullied mice. Mice are social creatures; when housed together, larger and meaner ones will quickly assert dominance. The little guys have it rough, usually showing signs of anxiety, depression and increased body weight within weeks.

The reason for their weight gain can be traced back to an increase in ghrelin, a hunger-causing (orexigenic) hormone produced in the stomach. Once released, ghrelin travels to the brain and binds to its receptors to increase calorie consumption. But not all foods are equal; new research from Carleton University suggests that ghrelin promotes the intake of comfort foods – specifically, carbohydrates- because they decrease the level of circulating stress hormones such as corticosterone.

In the study, researchers first measured the amount of chow that mice ate per day for 21 days. They then chronically stressed out one group of mice by putting a dominant bully into every cage; the two mice were separated by a see-through glass wall to reduce violence. Every day, the mice had 24hr access to a standard, high-carb chow and a 4hr-window to a fattier alternative. Compared to non-stressed controls, the bullied mice drastically increased their total calorie intake, paralleled by an increase in ghrelin levels but surprisingly normal corticosterone levels.

When researchers broke down in the increase in calories by the type of food, they uncovered an unexpected result: stressed-out mice did not eat more fat, but instead opted for more high-carb chow. In fact, this high-carb binge almost entirely accounted for the increase in total calorie consumption.

However, mice chow does contain ~50% of protein and fat. To rule out a preference towards these two macronutrients in combination, researchers repeated the experiment, but with sucrose solution as the alternative to high-carb chow. As before, stressed-out mice increased their intake of chow, but this time, they also doubled their intake of sugar water compared to their unstressed peers. At the same time, their corticosterone levels were normal, suggesting that they were coping fairly well in the face of daily terror.

Why is ghrelin triggering a preference for carbs? The answer might be internal stress management. When researchers feed both bullied and control groups the same standard chow (~50% carbs), effectively restricting access to stress eating, the bullied mice suffered numerous negative health effects. Their ghrelin and corticosterone levels shot through the roof. They had abnormally low blood sugar levels, signalling the onset of metabolic problems. They even showed signs of depression, refusing to swim when dropped into a deep container filled with water.

These data suggest that under stress, ghrelin levels rise and tip food preference towards high-carb rather than high-fat foods. To see if this is indeed the case, researchers turned to a strain of mice genetically engineered to lack ghrelin receptors. Normally, compared to wild-types, these mutants show similar patterns of eating and hormone regulation, although they tend to be slightly smaller. Once stressed, however, they didn’t respond by switching to the high-carb comfort chow, instead increasing their nibbling of fatty foods. Behaviourally, these mice could not cope – in the swimming task, they spent most of their time immobile, succumbing to their fates.

Researchers aren’t yet sure why ghrelin-induced carb – but not fat – intake helps to manage stress. One reason could be bioenergetics: stress alerts the brain that more energy is needed (and soon!) through ghrelin, which in turn increases the preference for glucose – a fast and efficient energy source. Or it could just be a matter of comfort. These mice grew up on standard mice chow, which just happens to be high in carbs. Perhaps, just like you and me, mice simply prefer familiar and comforting foods after a long, stressful day.

Brain, livin’ on ketones – a molecular neuroscience look at the ketogenic diet

Edited October 3, 2013: A 2.0 version of this post can be found at Scientific American MIND Guest blogs, here. And here’s me talking about it. Feel free to check it out!


WARNING: Wall of text on the yummy neuroprotective effect of ketosis from a molecular neuroscience point of view. Proceed with caution.


Delicious neuroprotection on a plate (Don’t forget veggies!) source:

Remember when your high school biology teacher said that the brain absolutely NEEDS glucose to function? Well, that’s not entirely true. Under severe carbohydrate restriction, the brain can adapt and start burning ketones as fuel.

Originally devised as a therapy for drug-resistant epilepsy in children, the ketogenic diet (keto) has been gaining popularity lately. It’s a high fat, moderate protein and low carbohydrate diet (LCHF) designed to force the body to go into a state called metabolic ketosis. With the advent of books like “Good Calories, Bad Calories” and “Why we get fat”, LCHF diets are increasingly touted as the magic bullet to weight loss. While there is considerable interest in the medical community in using the ketogenic diet to manage metabolic syndrome or prevent cardiovascular disease, more attention has focused on its role in drug-resistant seizure management and (potentially) neuroprotective effects in brain damage. In the last decade, keto has been shown to improve memory in patients at risk for Alzheimer’s disease, stabilize mood in type II bipolar disorder, reduce symptoms in Parkinson’s disease and even ameliorate some behavioral and social deficits in autism. Keto also seems to decrease brain cancer progression. ALL without observable side effects. Although most of these studies were unblinded (hence placebo can’t be ruled out), the effect is still amazing.

What is going on in the brain? And why aren’t pharmaceutical companies racing to package keto into a convenient treat-all 3-a-day pill?

How does the body go into ketosis?

Simple speaking, strict carbohydrate restriction depletes liver glycogen and forces the body to turn to other macronutrients for energy. Proteins are metabolically costly to utilize (not to mention dangerous – heart is also a muscle), and is often used as a last resort. By providing adequate amounts of fat, the liver uses dietary and body fat as fuel and produces ketones. “Ketones”, or “ketone bodies” is actually an umbrella term for 3 different molecules, β-hydroxybutyrate (BHB), acetoacetate (ACA) and acetone. All three can be delivered into the brain and metabolically converted into ATP in both neurons and glia. The three are interrelated: BHB and ACA can convert into each other, while ACA can turn into acetone. Extra ketones are eliminated through urine, or in the case of acetone, breath.

What are ketones doing in the brain? Answer: it’s complicated

There’s a reason neuroscientists and neurologists still haven’t figured out why keto is so effective in treating epilepsy. Holistically, the body is now running in a different metabolic state with changes in hormone levels (to say the least) which influences the nervous system. Locally, the brain is running on 3 types of semi interchangeable ketone bodies, the effects of which often can’t be teased apart. Hence it’s hard to say whether specific molecular and cellular alterations observed clinically or experimentally in animal models are a direct effect of ketosis, or simply a secondary phenomenon. Nevertheless, several hypotheses have been put forward to explain keto’s neuroprotective effects.

Source: Melo TM et al. Neuronal–glial interactions in rats fed a ketogenic diet. Neurochemistry InternationalVolume 48, Issues 6–7, May–June 2006, Pages 498–507

Source: Melo TM et al. Neuronal–glial interactions in rats fed a ketogenic diet. Neurochemistry International
Volume 48, Issues 6–7, May–June 2006, Pages 498–507

An oldie turned newbie: local changes in pH

Ketone metabolism generate pH-lowering metabolites, hence a change in pH was proposed early on as a way keto influences brain function. However there’s no evidence that keto significantly lowers brain pH, although mild decreases in pH may be possible in local microdomains. This hypothesis is attractive as many receptors are modulated by pH, such as acid-sensing ion channel (involved in stroke) and NMDA receptors (involved in learning, memory and excitotoxicity in stroke/neurodegenerative diseases), which may explain keto’s possible effect in stroke protection or cognitive improvement. Discarded a while back, this hypothesis recently resurfaced as the mechanism behind keto’s positive effect on Type II bipolar disorder management, which relies on blood acidification.

A favorite: Bioenergetics?

Ketones can be turned into energy effectively by the brain. In fact, BHB may provide a more efficient source of energy for brain per unit oxygen than glucose. A microarray study showed that keto induced a coordinated upregulation of genes encoding energy metabolism and mitochondrial enzymes, increasing the number of mitochondria in the hippocampus, a brain area associated with learning and memory. This increased energy capacity has been shown to enable hippocampal neurons to better withstand low glucose exposure, which happens in stroke. Better bioenergetics is proposed to limit seizure activity by stabilizing neuron resting membrane potential (so they’re not as excitable) or activate KATP channels through adenosine release. There are no studies directly addressing if energy efficiency is the reason for cognitive improvement in neurodegenerative diseases under keto, or if it contributes to enhanced cognitive performance in healthy individuals.

Cute as it is, there's not a hell lot of evidence.

Cute as it is, there’s not a hell lot of evidence. Source:

Another favorite: Antioxidative & anti-inflammatory effects?

Mitochondrial respiration, while generating ATP, also produces many reactive oxygen species (ROS). An acute increase in ROS is associated with stroke damage, while accumulation of ROS is one of the major hallmarks of aging and age-related neurodegenerative diseases. Keto can induce upregulation of mitochondrial uncoupling proteins (UCPs) in rat, which correlates with decreased ROS generation and increased resistance towards chemically induced seizure. Keto also increases the body’s own antioxidant defense system, namely glutathione levels in the hippocampus and protects mitochondrial DNA from ROS damage. If, and how, these antioxidative effect relate to neuroprotection is not yet clear.

Poly unsaturated fatty acids (PUFA) in the keto diet, such as DHA and EPA have garnered a lot of attention. Some evidence links them to decreasing neuronal excitability in hippocampus, which may contribute to decreasing seizure generation. PUFAs can also directly act on receptors called peroxisome proliferator-activated receptors (PPARs), the latter of which translocates to the nucleus and shuts down expression of pro-inflammatory factors. As inflammation increasingly recognized as a contributor to seizures, Alzheimer’s and metabolic syndrome, this mechanism may be a crucial one in keto’s favorable effects.

Maybe: direct drug-like actions of ketone bodies

Direct injection of ACA and acetone into animal models of epilepsy prevented seizures, hinting that ketone bodies may directly suppress seizure activity. However, other studies show that ketone levels may not correlate with seizure control. BHB and ACA have also been proposed to directly influence excitatory/inhibitor neural transmission. However, direct application of the two ketones had no effect on (1) excitatory responses in hippocampal neurons after stimulation (2) spontaneous epilepsy-like activity in a brain slice model of epilepsy (3) whole-cell currents evoked by glutamate, kainate, and GABA in cultured hippocampal neurons. Looks like a nail in the coffin for that theory. As far as I know, direct actions of ketone has not been linked to neuroprotection.

 Directly inhibiting cell death?

Keto seems to suppress the expression of pro-cell death proteins such as caspase-3 and clusterin (both of which mediates cell death in Huntington’s disease, among others), which correlates with enhanced recovery from seizure episode or stroke in patients. How much of a role this mechanism plays in disease states is still unknown.

Putting it all together: no pill yet!

The effects of keto are multifactorial and complicated. At the moment it’s impossible to tease apart which mechanisms are the driving forces behind keto’s powers, and which ones are secondary manifestations. Or they may operate equally, who knows? Hence packing everything up into a neat little keto pill is going to require a lot of effort (… …don’t even mention raspberry ketones!).

In the end, what do all these data tell us? A ketogenic diet with calorie restriction is most likely beneficial to weight loss. It is effective in controlling seizures in children and adults. It may improve cognition in patients with neurodegeneration or enhance mood stability in patients with Type II bipolar disorder. And that’s a BIG “may”. Without randomized controlled trials, it’s really difficult to say.

What about keto as a potential therapy (or adjunct therapy) for neurodegeneration? As increased ROS accumulation and mitochondrial dysfunction are common threads in age-related neurodegenerative diseases, it is conceivable that keto could be beneficial with its antioxidative and anti-inflammatory actions. To what degree is anyone’s guess.

Pass the bacon, maybe?

The ketogenic diet (along with other low-carb diets) is gaining popularity as a weight-loss measure. Some go on the keto diet because they experience “fewer sugar crashes, enhanced energy levels, mental clarity and decreased hunger”. A quick browse through progress photos on is probably enough to convince most people with a few extra pounds to give the diet a shot. Based on the above studies, keto is touted as a safe, effective tool for weight loss, with the added bonus of improved cognition. A few studies in epileptic children and healthy volunteers demonstrate that keto exterts a biphasic effect on cognition, with initial lethargy and subsequent heightened vitality, physical functioning, and alertness. Whether this translates into overall cognitive enhancement remains to be seen.

What are the potential side effects? A small study involving 21 obese women showed impaired higher cognitive function after 28-days on the keto diet. On the contrary, another study involving 83 obese patients showed improved blood lipid profile after being on a 24-week ketogenic diet without significant side effects. A caveat of most of these studies is the lack of an adequate control group, making results hard to interpret.

Some have also raised concerned regarding metabolic and long-term complications. Children following ketogenic diets have higher rates of dehydration, constipation, and kidney stones. Other reported adverse effects include hyperlipidemia, impaired neutrophil function, optic neuropathy, osteoporosis, and protein deficiency. However, ketogenic diet for the management of seizure is different than that for weight-loss. The former generally requires 80-90% fat calories (although this has decreased slightly in the Modified Atkins Diet) while the latter proposes ~60% fat calories with sufficient protein for muscle maintenance.

Whether keto promotes cognitive improvement and neuroprotection in the general public remains to be seen. While waiting for science to catch up though, I’m going for that bacon, spinach & cheese omelet. For science!

Edited Sep 2,2013: For those interested in exploring more, here is an accessible journal review that looks at potential therapeutic uses of nutritional ketosis in many other diseases. Note I am not promoting using keto as a sole treatment option – if there are efficient pharmaceuticals available please do not forgo them in favour of ketosis.


Masino and Jong. 2012. Mechanisms of Ketogenic Diet Action. Jasper’s basic mechanisms of the epilepsies. 4th ed.

Hallböök T, Ji S, Maudsley S, & Martin B (2012). The effects of the ketogenic diet on behavior and cognition. Epilepsy research, 100 (3), 304-9 PMID: 21872440

Dashti HM et al. 2004. Long-term effects of a ketogenic diet in obeses patients. Exp Clin Cardiol. 9(3): 200-205.

Rho, J., & Sankar, R. (2008). The ketogenic diet in a pill: Is this possible? Epilepsia, 49, 127-133 DOI: 10.1111/j.1528-1167.2008.01857.x

Phelps, J., Siemers, S., & El-Mallakh, R. (2012). The ketogenic diet for type II bipolar disorder Neurocase, 1-4 DOI: 10.1080/13554794.2012.690421

Ruskin DN, Ross JL, Kawamura M Jr, Ruiz TL, Geiger JD, & Masino SA (2011). A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington’s disease. Physiology & behavior, 103 (5), 501-7 PMID: 21501628

Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, & Clegg DJ (2012). Dietary ketosis enhances memory in mild cognitive impairment. Neurobiology of aging, 33 (2), 2147483647-27 PMID: 21130529

Denke, M. (2001). Metabolic effects of high-protein, low-carbohydrate diets The American Journal of Cardiology, 88 (1), 59-61 DOI: 10.1016/S0002-9149(01)01586-7

Chewing and spitting – a neglected symptom?

This is a cross-post from the wonderfully informative Science of Eating Disorders blog. ScienceofED covers a broad range of peer-reviewed research articles related to all aspects of eating disorders. Head over and check it out!

Eating disorders come in all shapes and sizes, but all of them are characterized by the same goal: to avoid weight gain or induce weight loss. While behaviors such as food restriction, purging and laxative abuse are relatively well studied, chewing and spitting (CHSP) is a  less studied symptom. A simple Google search, however, reveals over 1.5 million results for the term “chewing and spitting..  Results often links to blog posts or Tumblr pages where CHSP sufferers confess their guilt, disgust and obsession with the behavior.

What is chewing and spitting? How does it relate to other disordered eating behaviors, such as restrictive eating or binge eating?

Guarda AS et al. Chewing and spitting in eating disorders and its relationship to binge eating. Eating Behaviours 5 (2004) 231-239

What is CHSP?

Chewing and spitting describes the pathological eating behavior where the individual chews a variety of enjoyable foods, and spits it out to avoid undesirable consequences of weight gain (Mitchell et al, 1988). This seemingly “smart” workaround allows them to enjoy the taste of foods they usually deny themselves. However, CHSP is described as “driven and compelling,” often leading to uncontrollable episodes in which the individual chews and spits out large quantities of food. This type of behavior often results in social isolation, severe food obsession and financial difficulties.

Given the phenomenological similarities between CHSP and binge eating, CHSP was previously mostly examined in the context of bulimia nervosa (BN). While chew and spit is fairly common in patients with BN (64.5% of 275 patients with BN over the course of their lifetime), few patients engaged in the behavior continuously (Mitchell, 1985). In fact, chew and spit was considered an intermittent purging behavior used in place of self-induced vomiting or laxative abuse. A more recent survey  of individual with anorexia nervosa (AN), BN and eating disorder not otherwise specified (EDNOS) revealed that chew and spit was not limited to patients with BN (Kovacs, 2002). Patients who reported engaging in this type of behavior in the AN and EDNOS group demonstrated more disturbed eating behavior than their non-chewing and spitting counterparts.

In a study by Guarda and colleagues, , the authors set out to evaluate the prevalence and frequency of chew and spit in patients with AN, BN and EDNOS, and compare psychometrics between individuals who have this behavior compared to those who do not. Self-report questionnaires included the Beck Depression Inventory (BDI), which measures depressive symptomatology, and the Eating Disorder Inventory-2 (EDI-2) questionnaire, which measures eating disorder symptomatology. Overall, 301 patients were surveyed.

So what did they find?


1)   Overall prevalence: 34% admitted to one episode of CHSP in the month prior to admission, with 19% engaging in the behaviour several times a week (CHSP+).

2)   Overall, compared to patients who did not CHSP or did so once a week or less (CHSP-) CHSP+ patients were younger, significantly more likely to abuse diet pills, engage in excessive exercise, skipping meals and restrict fat and calories. The authors further examined if this difference in disordered eating occurred in all groups (AN, BN and EDNOS), and found that it was seen only in the AN group,. In other words, AN patients who engaged in CHSP reported more of the above behaviors than AN patients who did not. On the other hand, CHSP did not significantly alter eating behaviors in BN and EDNOS groups.

3)   Overall BDI scores were not different between CHSP- and CHSP+ patients, although CHSP+ patients were more likely to have considered suicide.

4)   There were no significant differences in mean length of stay as an inpatient, race or current employment between CHSP groups.

5)   There were no significant differences in BDI or EDI-2 in CHSP+/- patients who also engaged in binge eating.

Making sense of these results:

Contrary to previous belief, chewing and spiting is not limited to BN patients, but appears in similar frequency in patients with eating disorders in general. AN patients who engaged in CHSP tend to be more pathological in their disorder than AN patients who did not. CHSP did not influence eating behaviors of patients with BN or EDNOS. Surprisingly, CHSP is more commonly associated with other restricting eating behaviors than binging and purging.

However, as the authors noted, a limitation of this study is that they did not assess the amount of food consumed during each chew/spit episode or associated loss of control. Patients generally choose sugary or high fat food to chew and spit, hinting at a reward system deregulation that is also found in patients with binge eating disorder.  Future studies should address the macronutrient composition and amount of food consumed in a sitting as well as the individual’s state of mind to characterize this frequent eating disordered behavior and its reinforces.


Mitchell J et al. 1985. Characteristics of 275 patients with bulimia. American Journal of Psychiatry, 142, 482-485.

Mitchell J et al. 1988. Chewing and spitting out food as a clinical feature of bulimia. Psychosomatics, 29(1), 81-84.

Kovacs D 2002. Chewing and spitting out food among eating-disordered patients. International Journal of Eating Disorders, 32, 112-115.
Guarda AS, Coughlin JW, Cummings M, Marinilli A, Haug N, Boucher M, & Heinberg LJ (2004). Chewing and spitting in eating disorders and its relationship to binge eating. Eating behaviors, 5 (3), 231-9 PMID: 15135335

The complicated science of a simple pleasure (omnomnomnom) Go check it out. GO!

Karen K. Ryan and Randy J. Seeley.  Food as a Hormone. Science 22 February 2013: 918-919.

In an opinion piece in the February 22 issue of Science, KK Ryan and RJ Seeley argue for an alternative approach to look at diet and food – not in terms of nutritional epidemiology (“this is what healthy people eat”), nor in terms of macronutrients (“fat makes you fat!” “sugar makes you fat!”), but to view food as a grab bag of exogenous (coming from the outside) hormones.

Wait, what!? Food as hormones?

Hormones are long-range messengers that certain cells spit out into the bloodstream to act on other cells. Hormones can either bind to receptors on the cell surface(like Human Growth Hormone), or activate receptors in the cell nucleus and activate gene expression (like testosterone). Chemically, hormones are not that special – they’re usually short amino acid chains (peptides), fatty acids (lipids), or modified types of aromatic amino acids called monoamines. What they’re called doesn’t really matter – what’s important is that some of these chemicals can be found in the stuff we eat.

A well-studied example is omega-3 fatty acid, which has been shown to boost heart health, lower risk of stroke, and (may) help with weight loss and depression (WebMD). From a standard biochemical point of view, where omega-3 is regarded as an energy source, these specific effects are difficult to explain. A study by DY Oh yields a clue: omega-3s can not only be used as an energy source, but can also bind to and activate a receptor called GPR120 which is expressed on fat and muscle cells. Since loss of GPR120 activation is associated with weight gain, inflammation and inadequate blood sugar control, it is conceivable that omega-3 may directly control your metabolism through its activity on GPR120.

Omega-3 isn’t the only example of food directly acting on your cells. Branched-chain amino acids, such as Leucine, are often consumed by fitness enthusiasts as supplements to build muscle.  Why would Leucine be superior to a “straight” amino acid, such as glycine? Leucine can directly act on a central growth-regulating pathway called mTOR. In the periphery (body), mTOR activation can induce increased translation of components of skeletal muscle, leading to bigger muscle growth. In the central nervous system, mTOR activation signals satiety (feeling of fullness), and so can reduce food intake and body weight. Not bad for a simple amino acid found in cottage cheese!

There are many more similar examples, all demonstrating that the relationship between foodstuff and our bodies is not simply one of energy consumption.  Following this line of thought, Ryan and Seeley propose that we should design diets “from the bottom up” – based on how they act on signalling systems (such as mTOR) that we know are linked to metabolic diseases.

It is an interesting proposal, though (traditional foodie as I am) I have the nagging feeling that this seems too much, too soon. How much do we REALLY know about what’s going on at the cellular level? For any food component, how much gets used as energy and how much is left to directly act as a hormone? Does the interaction between components alter signaling abilities? How does digestion and exercise fit into the gist of things?

While a lot of the above research has gone into fitness nutrition planning and fad diets, it’ll probably still be a while (if ever) before we enter the realm of “designer diets”. In the meantime, GIMME THAT STEAK!

More reading (paywall):

1) Omega-3: D. Y. Oh et al., Cell 142, 687 (2010).

2) Leucine reducing food intake: D. Cota et al., Science 312, 927 (2006).

3) Effect of Leucine on protein synthesis:

Orginal source: Merrick, W. C., & Hershey, J. W. B. (2000) The pathway and mechanism of initiation of protein synthesis. In: Sonnenberg N, Hershey JWB, Mathews MB, editors. Translational control of gene expression. Cold Spring Harbor Laboratory Press.

Lazy source:
Ryan, K., & Seeley, R. (2013). Food as a Hormone Science, 339 (6122), 918-919 DOI: 10.1126/science.1234062

#SfN11 I’m eating because I can’t remember my last meal!

#SfN11 blogging:

Poster 410.01

To eat or not to eat: Hippocampal involvement in meal onset.


1Neurosci. Inst., 2Neurosci. Inst. and Dept. of Psychology, Georgia State Univ., Atlanta, GA; 3Psychiatry, Weill Cornell Med. Col., New York, NY; 4Neurol., Georgia Hlth. Sci. Univ., Augusta, GA

TL;DR: Dorsal hippocampal neurons expressed Arc 7min after feeding; inhibiting dHC after eating shortened the time before subsequent meal -> dHC might be involved in meal onset by forming a memory of a previous meal.

A feast for the brain and body...if you remember it!

Across the animal kingdom, eating usually happens in bouts. Whether or not to start eating (or “meal onset”, in neuroscience lingo) might seem to be a simple decision; however, the neural mechanisms underlying the motivation to begin eating are surprisingly complex and poorly understood. So why do we begin eating?

Perhaps the simplest answer is because we feel hungry. Indeed, adipose (fatty) tissue and the gut can send out physiological signals relating to energy balance to the hypothalamus, which in turn regulates our feeding behaviour. Brain areas involved in decision making and emotion, such as the forebrain and amygdala, can also influence our motivation to start eating (hello dieting and emotional binging). Many exciting findings have come out of studies focusing on the above brain areas. However, recently a number of neuroscientists have turned to the hippocampus for more answers by asking the question: can the memory of consuming a meal influence the timing of our next meal?

How did the spotlight turn to the hippocampus (HC)? It is well known for its crucial role in learning and memory. Neuroanatomical tracings have found direct projections from hippocampal cell fields to brain regions that are known to be involved in feeding. In humans, functional magnetic resonance imaging show changes in HC activation in response to food stimulation and manipulations designed to increase interoceptive signals of satiety (the feeling of fullness). Maniputating the memory of a meal in healthy young women can affect how much they eat in a subsequent meal. Even more fascinating, patients with severe HC-related amnesia (who presumably can’t remember their last meal) show a reduced ability to suppress food intake when repeatedly given the opportunity to eat.

The question this current study asks is whether or not hippocampal neurons can form a memory of a meal and inhibit meal onset later on. The authors first trained rats to lick a sugar solution at specific times of the day. On testing day, after a sucrose meal, muscimol was directly injected into the dorsal hippocampus to inhibit its activity. Rats were subsequently monitored for 60 minutes to see if there are changes in eating behaviour. Compared to the controls, who received a vehicle injection, dHC-inactivated rats waited a shorter period of time before eating their next meal (as measured by the inter-meal interval), ate for a longer time during the next meal, thus overall displaying less satiety. Inactivation of the dHC also prevented a correlation between the size of the preceding meal and the onset of the next meal, meaning that how much the rats’ ate stopped influencing how much they later on ate. All these behaviour observations suggest by inactivating the dHC, rats don’t form a memory of a preceding meal, hence ate the next meal as if they hadn’t eaten not long ago.

In order for the dHC to be involved in meal onset, the neurons will have to be activated at the time (and shortly after) the rats started eating to code for this memory. This is what the paper next looked at. In the experimental group, the authors fasted the rats, then gave them a sucrose meal before sacrificing them to probe for Arc mRNA, an immediate early gene that points to neuronal activation. The control group were also fasted but did not receive the last meal. They found that an eating episode significantly increased the percentage of CA1 neurons that expressed Arc in the experimental group compared to their caged controls, suggesting that food consumption may induce synaptic plasticity in dHC neurons.

In all, this study suggests that dHC neuronal activity is involved in inhibiting meal onset. Granted, it’s a very preliminary study, but the results are fairly interesting. Some more controls are certainly needed. Is Arc activation coding for meal onset or the general context of feeding? Will it activate if control rats received a last meal of water instead of not getting anything? What happens if rats receive an injection of sucrose instead of voluntary eating? Can inhibiting dHC activation change an animal’s eating behaviour in the long run (60 minutes is a very short time)? How does the dHC-hypothalamus circuitry interact with other circuitries involved in feeding behaviour?

We’re a long way from the authors’ last conclusion that “impaired HC functioning may contribute to snacking and the development of obesity”, but it’s a cool field.


J Neurosci. 2007 Jun 13;27(24):6436-41.

Medial prefrontal cortex is necessary for an appetitive contextual conditioned stimulus to promote eating in sated rats.

Behav Neurosci. 2010 February; 124(1): 97–105.

Hippocampal Lesions Impair Retention of Discriminative Responding Based on Energy State Cues.