A Penny For Your Thoughts, and $100 For Your Fat!

It's been some time since my last post. Turns out trying to start something new is not easy, as anyone who has tried to make or break a habit knows. This is something that many people that struggle with weight loss already know. But what can make changing your lifestyle easier? In the U.S.A. we have greatly diminished smoking through legislation that makes it inconvenient and expensive to smoke. This idea is now being actively applied to creating a more healthful food environment that promotes weight loss. Probably the most publicized "bad boy" of the food world is sugar sweetened beverages. Vending machines are being removed from public schools, limits are being placed on the size of sugar sweetened beverages you can purchase, and proposals for taxes on sodas have been made (but usually are not actually passed). So is all of this political interference doing anything? Science Says...Maybe, maybe not (of course science gives such a flimsy answer). The research as to whether there is a difference on our waist size or diabetes rates after attacking sugar sweetened beverages is thus far inconclusive for many reasons, most notable is the fact that this is all so new and it takes some time to see large changes.

So, let's address this issue from the other side. Instead of punishing people for wanting to drink a root beer each and everyday, could we instead give them money if they don't? You may have heard about schools in Ohio and Washington D.C., among others, that are paying their students to attend class and behave. While this has been met with plenty of controversy, it is an interesting idea that may expand to weight loss. In 2008 a study was published in the Journal of the American Medical Association that demonstrated the effect paying people to lose weight has on their ability to do so. Participants in this study were overweight (BMI was between 30 and 40) but overall healthy. There were randomized into one of three groups: the control group was given a weight loss goal and a scale. The deposit contract group was allowed to contribute $0.01 to $3.00 a day, and that amount was matched by the researchers. At the end of a month, if this group reached their weight loss goal they were refunded with their own money plus the matched deposit from the researchers. However, if they did not make their weight loss goal for the month they did not get any money back, so this group was mimicking what would essentially happen if we both rewarded people for weight loss but also punished them for lack of weight loss. The final group, called the Lottery group, got to choose a a two digit number. If this number was selected at the end of each month and that participant had met their weight loss goal they got either a $10 or a $100 monetary reward. Therefore, the Lottery group represents what would happen if we simply rewarded weight loss without the punishment. So what happened?

After 4 months of the study both of the incentivised groups loss an equal amount of weight (yay!), but the amount did not differ between the Deposit contract and the Lottery group. That means, in this study at least, it doesn't matter whether you reward and punish, or just reward people for losing weight. The study ended after 4 months, but after 7 months the researchers returned to the participants to see if their was weight regain. You can see above that even after 7 months those that were in either the Deposit contract or the Lottery group still had lost weight relative to their initial weight, but these differences in weight loss weren't significant when comparing them to the control group.

These same researchers published another article about the same participants, this time looking only at the comparison between the control group and the Deposit contract group. This study lasted 8 months, and you can see below that the Deposit contract group decreased their weight relative to their baseline measurement. Again, at 17 months post-study initiation when the participants were on their own there was no difference in weight loss between the two groups.

So what do you think? Is it worth paying people to lose weight? And how would this cost compare to the financial burden obesity and its related illnesses already put on us? Most importantly, would something like this ever get passed at the federal level in my life time without an anti-socialist revolt? Is Scienticklish getting political???



Volpp, KG, et al. Financial Incentive-Based Approaches for Weight Loss: A Randomized, Controlled Trial. JAMA (2008)

John, LK et al. Financial Incentives for Extended Weight Loss: A Randomized, Controlled Trial. Journal of General Internal Medicine (2011)

This is a great review of studies through 2010 that have looked at incentivising weight loss:
Robert Jaffery. Financial incentive and weight control. Preventative Medicine (2012)

The Atkins Diet Debate Continues

A recent article in the New York Times has gotten a lot of attention among dieters and nutritionists alike. In this piece, a long-time obesity researcher and physician is asked about a study published in the Journal of the American Medical Association last month. In this study, a group of overweight or obese people were placed on a calorie restricted diet until they lost 10-15% of their body weight. Then the study participants were randomized to a either a high protein, high fat and low carbohydrate diet (similar to the Atkins diet), a low fat, high carbohydrate diet (similar to what the USDA recommends Americans eat), or a diet in between, with the carbohydrates being more complex in nature and having a low-glycemic index, meaning that these carbs were from fiber in whole grains, fruits and vegetables as opposed to processed foods or white flour. Each of these diets were formulated to contain the same amount of calories, this way the researchers could focus on how the source of the calories rather than the the amount of calories affects weight loss.

The participants received each diet type for 4 weeks, and their resting energy expenditure (REE - the amount of calories your body needs to burn just to keep you alive) and total energy expenditure (TEE - the amount of calories you burn for everything you do) were measured. If you're trying to lose weight you would hope that your REE and TEE are high, because the more calories you burn the less fat you're going to be walking around with. You can see from the graph below that there was a slight decrease in REE and more substantial decrease in TEE when the participants ate the low fat, high carbohydrate diet relative to the high protein, low carbohydrate, Atkins like diet.

The authors of the study go on to say that they can't explain this change in TEE by an increase in metabolism caused by changes in thyroid hormone concentrations, or by the amount of physical activity each participant had. They hypothesize that a low carbohydrate diet may increase your TEE by changing other hormones in the body, or that the differences in metabolism of proteins, fats and carbohydrates may be responsible. Dr. Hirsch disagrees, stating that this TEE effect is probably due to the fact that when you are on a low carbohydrate diet you lose a lot of your water stores, and because lean body mass includes those water stores, your lean body mass will actually decrease. Because TEE is usually calculated as calories per unit lean body mass, you can calculate an artificial increase in TEE when the participant's lean body mass goes down.

I have to say that I like Dr. Hirsch's perspective on this, not because I'm strongly against a low carbohydrate diet (just strongly against a high meat one), but because he ultimately concludes that if you want to lose weight, you should just eat less of whatever it is you're eating already. As exemplified by the Twinkie diet, this works. You can eat Twinkies all day if you want and still lose weight, as long as you only take a micro-bite of the Twinkie and stop the instant you're no longer starving.


Ebbeling, CB et al. Effect of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. Journal of the American Medical Association (2012)

Raisins Lower Your Blood Pressure!

Wait, what? I just got this study in my inbox and felt it was worth a Scienticklish reply. I have 30 minutes before my lab protocol requires my attention, so lets see if I can get through this post quickly.

Looks like some researchers in Louisville, Kentucky were looking at the effects of eating either raisins, or cookies and crackers, what they called "snacks" on participants' blood pressure. Turns out if you eat the same amount of calories from raisins as you do from cookies and crackers three times a day and you are at risk for high blood pressure, you may actually lower your blood pressure. The lowering effect was anywhere from 4 to 8 mmHg for the systolic blood pressure, and a reduction between 2 to 6 mmHg for diastolic blood pressure, meaning that if your normal blood pressure was 133 over 82, like these study participants, the end result of eating raisins 3 times a day for a minimum of 4 weeks are a blood pressure of about 128 over 78. Still higher than what's considered a healthy blood pressure, but better.

 What does this mean? Of course! Raisins are better for you than cookies! The researchers point to the fiber or antioxidants you get from raisins that you're missing in crackers and cookies. I point to the fact that its raisins vs. cookies. I think you can figure out which one is better for you.

      vs    

Should we be trying to get people to snack on raisins? Well, this is just an abstract that was presented at a recent conference, meaning I can't find the details of the study (easily). So, I would have to say that it depends on the amount of total calories these snacks are adding to the diet. I would like to see the California Raisins go head-to-head with the Cookie Monster.


Bays HE. et al. Raisins and Blood Pressure: A Randomized Controlled Trial. Journal of the American College of Cardiology (2012)

Colonizing the Colon

Over the recent Memorial Day weekend Mr. Scienticklish and I were lucky enough to participate in not one, not two, but THREE barbecues! There was a lot of corn, burgers and sweet treats to go around, but probably the most interesting food we consumed was Water Kefir, thanks to a new friend met at BBQ #2. While in conversation, this new friend was referred to as the "King of Fermentation" - a title that I'm sure only a small demographic is excited to have. Our new friendship resulted in him offering up various bacterial and yeast cultures, including a sourdough bread starter and Kefir grains. Similar in theory to the fermented Kombucha beverages, Water Kefir uses various bacteria strains (together called Kefir grains) to break down sugars. When you make Water Kefir yourself you add table sugar or fruit juice to feed the bacteria, which they use to produce CO2 and a small amount of ethanol, making the drink bubbly and about 0.5% alcoholic. In the end you get a fruity, carbonated drink that is very low in calories, high in active bacteria cultures and absent of the vinegar taste you find in Kombucha. The one we sampled the next day was so good in fact that we wondered why the producers chose to market the drink as a pro-biotic, fermented drink as opposed to a healthy alternative to soda? Anyway, if you can find some you should try it for the taste alone, if not for any health benefits you may get from the bacteria.

Don't be fooled by those good-for-nothing amateur biotics

Pro-biotic foods and beverages have been getting a lot of hoopla lately. I think it's pretty exciting stuff too. The more we learn about the functions of all of those bacteria living in our gut, the more we realize how integral they are for our own health. These colonies of bacteria exist mostly in the colon, some make it past the ileocecal valve into the small intestine, but when we think of the gut microflora generally we're thinking of the colon. So how did this bacteria get there? When you were a fetus you were sterile, it wasn't until you were born that mom passed on her bacteria to you as you traveled through her birth canal. As expected, babies that are born via cesarean section have a different composition of gut flora than those born vaginally. After delivery, it seems like almost everything, and then nothing, can change your gut flora. Some studies show that what the infant eats (breast fed versus formula fed for example), and whether the baby was born in a hospital or at home can affect what bacteria colonizes their gut. However when adults are given pro-biotic foods it's still not certain what the results are. For example, the live cultures in the yogurt you eat may be doing something beneficial while they're passing through your gut, but whether they hang around and make your colon their new home isn't really known yet.

The war in your colon?

A potential way to change what bacteria grow in your gut is to change what you feed them. For example, when comparing vegans vs vegetarians vs meat eaters you see different types of bacteria growing in the colon. Additionally, lean people and obese people also have a different world of bacteria taking up residency. To study the latter in more detail, researchers looked at the types of bacteria growing in the colons of obese and lean mice. They also looked at the contents of the fecal matter (taken from the caecum) and found differences in lengths of fatty acids between lean and obese mice (part a in the figure below). Next,they looked at differences in fecal material between lean and obese mice, finding that the obese mice had less energy (kcal) per gram of waste, perhaps showing that the obese mice were better able to absorb that energy into their blood stream as opposed to pooping it out (part b). Finally, in what I think is the coolest part of this experiment, the researchers did a "fecal transplant" into mice that were devoid of bacteria in their gut. This means that someone, a lowly grad student I'm sure, took poop from the lean and obese mice and fed it to the bacteria-free mice so that those bacteria would grow in the colons of the new mice. And now we know why people think scientists are crazy... BUT look at the cool results in part c below! The mice that got poop from lean mice (+/+) had less than half the percent increase in body fat compared to mice that got poop from obese mice (ob/ob). Keep in mind that these mice were on the same diet, and the mice that gained more weight didn't eat any more food than the mice that didn't gain the weight. Perhaps the bacteria from the obese mice helped breakdown the nutrients to make them more readily absorbed, thus permitting those mice to take in the energy and store the fat. So now we need to convince the world that the future of weight loss lies in fecal transplants.

I'm realizing that this is becoming quite a long blog post about poop and colons. I'm also realizing that I may have a strange fascination with these topics. I haven't even really got into what these little creatures may do for our health. Perhaps a future post about Jamie Lee Curtis and her empty promises with her Bifidus Regularis will be necessary. As for now I'm going to leave you all to digest this fecal-filled post, just like those poor mice.

Zimmer, J. et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. European Journal of Clinical Nutrition (2012)

Penders J. et al. Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy. Pediatrics (2006)

Turnbaug, P.J., et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature (2006)

Shiver Me Thinner?

In making the move from the sunny desert of the southwest to the chilly northeast I've often wondered what this harsh climate is doing to my body. Of course my mind automatically goes to all of the bad things caused by extreme cold - hypothermia, slipping on ice, liver failure from all of the whiskey needed to keep warm - but turns out there may be some metabolic advantages to being in a cold environment due to a potential increase in a type of fat tissue called brown adipose. While brown adipose has become a growing area of research in recent years, it was originally discovered decades ago. The reason for the newly found interest is because until recently it was thought that only newborn babies and non-human mammals had brown adipose. The belief was that as newborn babies grew into adolescents they lost the brown adipose and were left with the normal white adipose tissue. So why does discovery of this special type of fat in human adults matter? Because it may increase the use of energy from the food that we eat for heat production in a process called non-shivering thermogenesis, which gives the body a mechanism to provide heat when living in a cold environment. Because this energy is being "burnt off" as heat, it won't be stored in your growing beer belly. So maybe you can't shiver yourself thinner, but maybe you can non-shiver yourself thinner.

The name "brown adipose tissue" comes from the look of this tissue under a microscope. It's brown, and it's adipose tissue. Sometimes science can be straight-forward. The brown color is from extra mitochondria, which are the organelles within the cell that make energy (in the form of ATP) for your body. In order to do this, the mitochondria keep an electrical gradient across its inner membrane by separating the negatively charged electrons from the positively charged protons (in the form of hydrogen atoms). The electrons then are transported through a series of proteins collectively called the electron transport chain (again, straight-forward), until the end of the chain. At this point the positive hydrogen atoms are allowed to flow back through the membrane, releasing energy that is refashioned into ATP molecules by the enzyme ATP synthase (See the picture below for the cartoon rendition of the ETC). These molecules are then passed on to every cell in the body, keeping us alive. So you can imagine that if this simple flow of hydrogen atoms down the energy gradient holds enough energy to keep each cell going, it also must be able to release that energy as heat. This is where we get back into brown adipose tissue and non-shivering thermogenesis. There is a protein called Uncoupling Protein (UCP) that is highly expressed in brown adipose. UCP will basically give the hydrogen atoms another channel to travel through the mitochondrial membrane down the energy gradient. This time instead of using that energy to make ATP it is released as heat, thereby raising the body temperature. This switch-over from ATP production to heat production causes the body to want to make more ATP, so the energy stores in your body that are the starting substrates of the reaction start to get used up.

Remember the ETC?

Those of you that are pharmacological-minded may ask why we don't just make a weight-loss drug that uncouples the electron transport chain? Well...because it's a poison. Back in the 1930's people started taking an ETC uncoupling chemical called dinitrophenol, DNP for short, to lose weight. It worked great! But, it also resulted in your mitochondria not being able to make any ATP for your cells to survive. No ATP = no energy = no you! Unfortunately it looks like there is still an illegal market for DNP and people are still taking it. This is pretty scary stuff, I don't think you want to mess with cellular respiration. Plus it seems the body does this for you to a degree if you have brown adipose tissue, which you probably do. The amount of brown adipose that you have seems to be correlated with age (the younger you are, the more you have), sex (females have more), fasting blood glucose (a lower fasting glucose is associated with more brown adipose), and BMI (the leaner you are the more non-shivering you may potentially do). Interestingly, the activity of the brown adipose seems to correlate with the mean outdoor temperature of where you live, so that the warmer the climate, the more glucose is taken up by the brown adipose and potentially used for heat production (See graphs below). This study just so happened to take place in Boston, so these subjects also get to experience the New England chill alongside me.

Yes, you read that right, those with a lower BMI actually seem to have more brown adipose. Why? Well, maybe they need more heat because they have less fat to act as insulation, or maybe it's the extra brown adipose that is letting them stay thinner in our obesogenic environment, no one really knows yet. Also something interesting to note, those with a lower BMI or % body fat also had more active brown adipose tissue, meaning the tissue is taking up more glucose out of the blood (see graph below). 

Okay, so I guess I take back my previous statements, you probably can't shiver yourself thinner, or non-shiver yourself thinner, but maybe when you are thin you can non-shiver yourself warmer? 

van Marken Lichtenbelt, WD. et. al. Cold Activated Brown Adipose Tissue in Healthy Men. New England Journal of Medicine (2009)

Cypess, AM. et al. Identification and Importance of Brown Adipose Tissue in Adult Humans. New England Journal of Medicine (2009)

Bartelt, A., Merkel, M. & Heeren, J. A new, powerful player in lipoprotein metabolism: brown adipose tissue. Journal of Molecular Medicine (2012)

Raspberry Ketones and Your Love Handles

In addition to spending my days chained to the lab bench, I also spend my time moonlighting as a teaching assistant for nutrition classes in the Boston area. In one such class the students were given the assignment to present a nutrient or food that is associated with preventative properties of certain diseases. One student group decided to focus on what is seemingly the next diet craze: raspberry ketones (RK). I thought this would would make a great Scienticklish post because it is a timely topic (having recently been aired on Dr. Oz) and the immediate anger I felt after Googling RK and weight loss and finding so much bad information riddled with lies! Thus, a post to get the facts out there. Science!

First, some background. Raspberry ketones are small molecules found naturally in red raspberries which give them their smell and flavor (see above for the molecular structure). RKs have been used by the food industry for years to put the flavor or raspberries into various treats. They are also used in various perfumes, soaps and lotions, so the synthesis and purification of RKs are nothing new. In the past decade some scientists started taking note of the molecular similarities between RK and capsaicin - the molecule that is responsible for chilies' spiciness that have been shown to increase metabolic rate. Intrigued by this resemblance, researchers in Japan began to study the effects of feeding RK to mice that were eating a diet high in fat. They published a study in 2005 that showed feeding RK to these mice increased lipolysis, or breakdown of fat and decreased the absorption of dietary fat. Overall, the mice fed larger doses of RK were lighter than the mice fed the high fat diet alone (See figure below). A high dosage seemed to be key: the mice that were fed a diet containing 2% RK by weight had a significant decrease in body weight, but the group of mice eating a diet that was either 0.5% or 1% RK by weight did not have any difference in body weight relative to mice fed a high fat diet alone. It's probably safe to bet that the amount of RK needed to see this effect is not available by simply eating raspberries, which brings us to the next published paper I'll discuss: a patent!

ND: Normal Diet;  HFD: High Fat Diet;  RK: Raspberry Ketone

Also in 2005, a different research group (associated with DSM, a leading producer of purified nutrients that are used in supplements and food products globally) published a US patent for a neutraceutical blend of the polyphenol found in green tea called EGCG and an RK precursor. This patented product demonstrated the ability to  prevent weight gain and obesity associated conditions (like type II diabetes), again, in rodents. Showing similar results, their now patented supplement prevented weight gain in both mice and rats fed a high fat diet or a high fat, high sugar diet.

So, should you be taking RK to get ready for the beach this summer? Well, so far it hasn't been shown to have any adverse effects (other than decreasing the size of your summer beer fund), but because published research in humans is so limited (i.e. non-existent), no one really knows if it is safe. More and more nutrition research is coming out to show that supplementation of large doses of a single nutrient are actually harmful for humans, so you should take caution before popping pills of any kind. Plus keep in mind that RK supplementation has only been shown to prevent rapid weight gain in mice that were eating a very high fat diet, you can't expect that it's going to behave the same in humans that are trying to lose weight. The nutrition community goes through these magical weight loss nutrients so quickly without much to show for it. Remember when I said the idea of using raspberry ketones for weight loss stemmed from using capsaicin for weight loss? Well, do you know anyone that has lost a lot of weight by taking capsaicin pills? Right. I hate to be the negative Nancy here, but the best way to lose weight is really to make some major lifestyle changes that include eating foods that will keep you fuller longer (high fiber, high protein), and constantly reminding yourself to keep moving. Yes, it's going to be hard and you're probably rolling your eyes at the nutrition community for sounding like a broken record, but it is what it is. In the end, you'll be better off trying to increase your intake of raspberries (along with other fruits and vegetables) than spending that cash on pills.

Yum!

Morimoto, C. et al. Anti-obese action of raspberry ketone. Life Sciences (2005)

Raederstorff, D. et al. Nutraceutical compositions comprising epigallocatechin gallate and raspberry ketone. US Patent Office (2005)

The Evolution of Cuteness

It’s one of my favorite stories in science: why we are programmed to think our babies are so damn cute. Besides giving parents bragging rights and feelings of pride and adoration, having our brains programmed to think our offspring are cute comes with evolutionary advantages. To better understand what those advantages are we will need to take a step back into the times when our ancestors were still spending most of their days swinging from branch to branch rather than running around on two legs. We needn’t be too imaginative, just think of how an ape moves around. Most of its time (when not adorably hanging around) is spent on 4 limbs. This means the joint between the hip and the upper femur doesn’t need to be able to bear a lot of weight. Because of this, the shape of the pelvis of an ape was, and still is, very different from the pelvic bone of a human. 

About 6 million years ago, the early human ancestors came down from the trees and began to discover all that the grasslands had to offer. Why? I think they were probably just sick of eating tree fruits all day and craved adventure! Due to this drastic lifestyle change, the skeletal structure of early hominids began to change as well. The hip began to adjust so that all of the body weight could be put on only two limbs for a significant amount of time. As the hip evolved to be more compact, so too did the birth canal which narrowed to give more strength to the hips for bipedalism. A smaller birth canal would be okay for your monkey-brained neighbor, but not for the superior intellect of yourself. As we went from apes to hominids the brain and the head size began to develop as well. This poses an obvious problem in human evolution: how on earth are we supposed to give birth to babies with increasing brain and head sizes while at the same time develop a narrowing birth canal? 

Schematic drawing of the birth canal sizes and fetal skull sizes in apes and humans. Looks like humans have it pretty bad!

An interesting conundrum, and one we have thankfully overcome! If you have spent any time around a newborn you know how completely helpless they are. Newborns need a more capable being to help them eat, burp, even hold their head up. Given that the size of human brains are substantially larger than other mammals that are completely capable upon birth, does this not strike you as odd? Additionally, consider the length of gestation for us humans. Nine months is a relatively long time, especially when the end product isn’t quite ready for life on its own. While fetuses are in the womb their brain and head size will develop to be as big as possible while still small enough to pass through the narrow birth canal. Then, after birth, the baby’s brain will continue to grow as the baby becomes more able to perform tasks like eating and holding a spoon. The soft connective tissue, or fontanels, connecting regions of the skull at birth will eventually fuse when the skull has reached its proper size. For quite some time after birth however, infants are dependent on others to help them survive. Without this help, infant survival would be impossible.

Enter the cuteness factor! Lucky for all of us parents have a natural affinity for their offspring when they are brought into this world because they’re perceived as cute! The baby fat, the forward facing, large round eyes and button nose all contribute to why we think infants (and some baby animals for that manner) are cute; and part of the reason why parents feel a compelling need to stick around and care for them. This has been given the technical, German term of Kindchenschema, roughly meaning childlike cuteness in some scientific literature. Interestingly enough, the ability to correctly select the “cuter” baby when presented with a cute and a less-cute picture of a chubby-cheeked test subject is stronger in women (see the photos below for an example). Perhaps Kindchenschema is another way, in addition to the oxytocin release women experience while breastfeeding their newborn, that the maternal instinct shapes new moms. 

Because cuteness makes something click in the parents’ brain causing them to want to care for the infant, the baby is given time to develop its brain and fuse its fontanels. Of course there are other theories of why newborns are seen as cute, one of which is simple natural selection. As the the theory goes, the children that were seen as the cutest got more food, love and attention from their parents, thereby growing up to be strapping, fertile adults that could pass along their cute-genes to their own plethora of offspring. This is a noteworthy theory, but I like to think that the evolution of cuteness derives from the infant’s need for love and attention right at birth. So in the end, when humans started to walk around and gather their food, babies started finding out a way to make us unconditionally love them. Those maniacal babies!  

Insert devious laughter here. 

1. Rosenberg, K. & Trevathan, W. Birth, obstetrics and human evolution. BJOG (2002)
2. Lobmaiera, JS. et al. Female and male responses to cuteness, age and emotion in infant faces. Evolution and Human Behaviour (2010)