nutritionwonderland

Category: Health & Disease

  • Alzheimer’s Disease as Type 3 Diabetes – The Glucose Connection

    Alzheimer’s Disease as Type 3 Diabetes – The Glucose Connection

    Glucose is the main energy source in all living cells, regardless if those cells are idly growing in a petri dish in a lab, in the leaf of your household plant, or one of the billions networked within the human body.

    In animals, cell get energy by directly eating foods with sugar, or by digesting more complex starches, such as the carbohydrates found in pasta and rice, into the simpler sugar, glucose, which is then easily absorbed into the bloodstream. But how the body handles those sugars – and how many sugars you bombard yourself with – can have wide ranging implications.

    The process is more complicated than you might think, as shown in the figure below.  So let’s take a closer look at exactly how glucose gets into cells – and how that could eventually lead to alzheimers.

    Understanding Glucose

    After chowing down on your favorite meal, glucose is literally coursing through your veins.  Being a small molecule, glucose is rapidly shuttled around the body.  It makes its way out of our blood vessels, and moves into the tissues of our body, primed to deliver energy to hungry cells.  But despite its ambition, it can’t cross the cell membrane to get to the inside of cells where it’s converted to energy.  Special proteins, called glucose transporters, line cell membranes and help pass glucose from the outside to the inside of cells.  There are several different types of glucose transporters found throughout in the body — for instance, GLUT-1 is found in erythrocytes (red blood cells) and the endothelial cells that line blood vessels.  GLUT-3 is found in neurons.  GLUT-4 is found in fat and muscle cells.

    Most glucose transporters simply simply act as a conduit, allowing glucose to passively move through the cell membrane.  But GLUT-4, the transporter found in fat and muscle cells, is rather unique, because it must be activated by the hormone, insulin.  The process goes something like this: the pancreas, sensing the glucose rush in the bloodstream after a meal, sends the hormone insulin to the rescue.  When near a muscle cell, insulin binds to a membrane protein called an insulin receptor.  This binding sends a chemical message to the GLUT-4 protein that it’s time to start letting glucose in.

    The Balancing Act of Glucose Transport at the Cellular Level

    The Balancing Act of Glucose Transport at the Cellular Level

    Most cells don’t require a constant source of glucose.  Rather, they can store an energy reserve as glycogen, giving us a backup boost of fuel after we’ve burned through all the available glucose.  You’ve inevitably heard the expression “hitting the wall” during a distance running competition, like a marathon.  Physiologically, “hitting the wall” means you’ve burned through all the glucose AND glycogen in your body, and now you’ve got to convert fat to energy, which is a much less efficient process, and leads to extreme fatigue.

    Diabetes

    Now that we have a basic understanding of how glucose acts in the body, let’s shift our attention to what can go wrong with this pathway.

    Diabetes, a disease affecting millions of people, occurs when something goes wrong with the insulin-glucose interaction in cells.  In Type I diabetes, there is simply not enough insulin circulating in the bloodstream.  Tissues that have GLUT-4 transporters, which require insulin to get glucose into cells, starve.

    Type II Diabetes Pathogenesis

    Type II Diabetes Pathogenesis

    In Type II diabetes, cells have become insulin-resistant, or “insensitive” to insulin.  This means that there is plenty of insulin in the bloodstream to go around, but either the hormone can’t bind to the insulin receptor, or once bound, there is no chemical message sent from the insulin receptor to the glucose transporter to start allowing glucose to enter.  The pancreas, sensing there is still a large amount of glucose in the bloodstream, releases more and more insulin, compounding the situation.

    In both Type I and Type II diabetes, the high level of glucose in the blood can damage organs such as the heart, the kidneys, or the eyes, just to name a few.  But as we’ve previously discussed, an increase in glucose circulating in the blood also means that there is an elevated level of insulin meandering through our body.  Although insulin’s primary function is to signal to GLUT-4 transporters that it’s time to move some glucose across the cell membrane, insulin is a hormone with far-reaching biological effects.  Let’s see what happens to my organ of choice, the brain, when levels of glucose and insulin skyrocket.

    Sugar and the Brain

    Now let’s talk about how energy is supplied to neurons, because it is a bit different than most cells in the body.

    Approximately 20% of our resting metabolic rate goes to power our brains.  This means our brains require more energy at rest than all of the muscles in our body, or our heart and kidneys combined.

    Energy in the brain must be supplied by a constant source of glucose, since limited stored energy in the form of glycogen exists.  When glucose levels in the blood drop too low, neurons will eventually stop functioning, and brain damage occurs.

    Given that insulin is required for glucose uptake in other parts of the body, early studies sought to determine if insulin had any effect in the brain. In 1979, researchers showed that the level of insulin in the brain determined how much food a group of monkeys consumed, but they could not produce a direct link to how insulin worked in the brain.

    Later studies found large amounts of both the GLUT-1 transporter, which carries glucose from the blood steam to brain tissue, and the GLUT-3 transporter, which moves glucose into neurons.  Since both the GLUT-1 and the GLUT-3 do not need insulin to initiate the process of moving glucose from one place to another, we prematurely concluded that glucose metabolism in the brain has nothing to do with insulin.

    It turns out that our initial thoughts were way off.  Fast-forward to present day, where we now know that neurons need insulin to survive.  We’ve actually identified several areas of the brain with neurons that have insulin receptors.  Two particular areas with insulin receptors, the cerebral cortex and hippocampus, are heavily involved in memory formation and organization.

    The hippocampus also has GLUT-4 insulin-dependent transporters, which are shuffled around to maximize glucose absorption in neurons when an animal is learning a new task.  Other studies have shown that glucose metabolism in the cortex is at least partially controlled by insulin.  Injection of insulin caused an increase in glucose uptake in the cortex, presumably due to either activation of GLUT-4 transporters, or by insulin stimulation of neurons that increased the need for cellular fuel.

    Is There a Link Between Diabetes and Alzheimer’s Disease?

    In Alzheimer’s Disease, funky, abnormal protein clumps collect in the brain.  Physicians and researchers call these protein clumps neurofibrillary tangles or amyloid-beta plaques, depending on whether they’re actually inside cells, or in the space between neurons.  Whether the proteins themselves are the cause or the result of the disease is still unclear.  Regardless, we know that Alzheimer’s Disease causes neurons to die, which leads to cognitive problems, such as memory issues and confusion.

     

    Alzheimer’s Victim

    Given the finding that glucose metabolism in the brain is not entirely independent of insulin, and the surge of Type II diabetes, scientists have developed an interest in how sugar acts on on brain diseases.  There are two lines of thinking when it comes to the link between Alzheimer’s Disease and diabetes.  The first says that the elevated levels of insulin, as seen in Type II diabetes, may cause Alzheimer’s Disease.  Studies point to insulin in causing neurofibrillary tangles to form inside of cells, as well as affecting the processing of the amyloid precursor protein, which form those senile plaques in between cells.

    The second theory of Alzheimer’s Disease and diabetes says that Alzheimer’s Disease is not caused by the increase in insulin from Type II diabetes.  Rather, there is improper insulin handling occurring directly in the brain.  People are calling this ‘Type III Diabetes’.

    A group at Northwestern University, led by neurobiologist William Klein, is leading the research behind this new potential form of diabetes that has its sights set on the brain.  The Northwestern group believes that small peptides, called amyloid-beta derived diffusable ligands (ADDLs), break away from senile plaques, and attack cells.  These ADDLs have been shown to remove insulin receptors from the brain, thereby impairing the synapse, which is the area where neurons connect to each other.  Klein’s group showed that certain drugs, which increased insulin sensitivity, eliminated the harmful effects of ADDLs on neurons, which according to Klein shows that ”bolstering insulin signaling can protect neurons from harm“.

    So Now What?

    For years, sugar has been the silent killer, slowly chipping away at our body’s sensitivity to insulin, and contributing to the obesity epidemic.  We still don’t have enough evidence to say for sure whether there is a direct link between Alzheimer’s Disease and diabetes.  But the fact that glucose- and insulin-signaling irregularities cause problems in the brain creates yet another reason to restrict the sugar and refined carbs in our diets.

  • California First State To Ban Trans Fats

    California First State To Ban Trans Fats

    Effective January 1st, 2010, California became the first state to ban restaurants from using trans fats in restaurants. While similar bans have been enacted in New York City and a few other cities in the US, this is the first time that trans fats are being banned from an entire state.

     

    Schwarzenegger Acts…

    The legislation was signed by Governor Schwarzenegger in 2008, giving the state’s 88,000 restaurants a little time to nix trans fats from their cooking. Under the new law, restaurants, delicatessens, cafeterias and other businesses classified as “food facilities” will, in the preparation of any foods, have to discontinue use of oils, margarine and shortening containing trans fats. It will cost cooks anywhere from $25 to $1,000 for a violation. Bakeries aren’t immune, either, and have to purge the trans fats from deep fried yeast dough and cake batter by 2011.

     

    Nutrition scientists have been warning of the dangers of trans fats for years now. While other dietary fats have redeeming qualities, trans fats seem to have none. They’re almost entirely man-made, created by adding hydrogens to other fats. This process, called hydrogenation, turns oils into the semi-solid margarine and other products that are associated with trans fats. These trans fats are useful because they have a longer shelf life, are hard enough to stay solid at room temperature, and yet can even be malleable cold. Unfortunately, there’s a big cost for those benefits.

    Trans fats, in general, are bad for you. They raise your risk of diabetes and heart failure, particularly by raising “bad cholesterol” levels in the body. But they don’t stop there. They not only raise LDL (bad cholesterol) levels, they lower HDL cholesterol levels – the good ones. In 2006, a scientific review of fats from the New England Journal of Medicine stated clearly that:

    “from a nutritional standpoint, the consumption of trans fatty acids results in considerable potential harm but no apparent benefit.”

    The damning evidence against trans fats comes from a study of 120,000 female nurses from 1976 to 1990. The Nurses’ Health Study found that the risk of coronary heart disease nearly doubled for every 2% increase in trans fat calories consumed instead of carbohydrates. Considering the same increase in risk takes a 15% increase in saturated fats and that eating the other unsaturated fats actually lowers heart disease risks, there seems to be no reason to eat trans fat at all. And if that weren’t bad enough, trans fats have also been linked to liver problems and even infertility.

    Many hail the new legislation banning them in the most populous state in the union as a step in the right direction for the American public. The incoming president of the American Heart Association, Dr. Clyde Yancy, is one of its biggest fans. “I think the potential here is real for a far greater understanding of the harms of trans fats, and to encourage more states to do the same,” he said when asked about the law’s enactment. Governor Schwarzenegger, too, has commended the state for its efforts.

    “California is a leader in promoting health and nutrition, and I am pleased to continue that tradition by being the first state in the nation to phase out trans fats,” the governor said in a statement. “Consuming trans fat is linked to coronary heart disease, and today we are taking a strong step toward creating a healthier future for California.”

    Many of the state’s restaurants had already dumped trans fats from their menu, cracking under the pressure of consumer demand. National chains like Wendy’s, Taco Bell, McDonald’s, and KFC have already started removing trans fats. But other restaurants are finding it harder to switch, as non-trans fat oils are harder to come by and far more expensive. Smaller restaurants have stated that the ban will force them to raise their prices significantly.

    While this new ban will make eating out healthier for Californians, it’s only a small step towards the state’s overall health. Trans fats can still be found all over in Cali’s grocery stores and supermarkets, as the ban doesn’t apply to packaged foods. Hopefully, the anti-trans fat movement will continue to gain momentum, and these unhealthy fats will become less and less prevalent in all of our foods. Kudos to California!

  • Deja Vu? FTC Sizes Up Food Marketing and Childhood Obesity

    Deja Vu? FTC Sizes Up Food Marketing and Childhood Obesity

    The breath of the obesity epidemic being witnessed in the United States is troubling.  Some states now show that over 30% of their respective populations are obese, with many of these metrics still growing.  Worse, the epidemic’s fastest acceleration has been in its youngest demographic: children (although that may finally be slowing).

    FTC Sizing Up Conference Logo

    Theories have been entertained to determine what is causing the obesity problem in children.  Sedentary activities like video games and television regularly are brought out to the whipping post as the cardinal reason for the rapid rise but another view, that of food marketing to youth, has received increasing attention.  That attention culminated in a summit put together by the FTC called Sizing Up.

    For older readers in our audience, this may seem to be a cruel reminder of the history behind this issue.  Back in 1978, the FTC made a move to ban just this type of advertising before it was stripped of that very ability by Congress later in 1980.  Fueled by the obesity epidemic, the FTC felt compelled to revisit the issue some 30 years later.  Nutrition Wonderland also felt compelled to attend the star-studded event (by government standards at least), with Kathleen Sebelius, the secretary of the US Health and Human Services department giving the keynote – and plenty of other notable attendees present.

    The View From Above

    Secretary Sebelius opened the conference with a keynote speech that was both informative and defensive.  She took her audience through some of the statistics about obesity, the most striking is that it will cost the US an estimated $350-400 billion dollars by 2020 to address the obesity epidemic if it continues to grow as it has in the past.  Remember those numbers are in 2005 dollars and inflation will likely raise that cost another 40-50%.

     

    A 2008 Map of Obesity Rates in US by State, note that red is +30%

    Her other thoughts were focused on what the FDA is doing to counteract the problem of advertising food to minors.  Namely, the FDA is doing a comprehensive review of what they term as ‘front of package labeling‘ (FOP).  This concept deals with all the eye candy food marketers use to indicate how healthy their products are – especially in the cereal industry.  The industry sponsored Smart Choices program, which the industry was doing to coordinate their nutritional packaging information (deemed a debacle by the agency), was the unspoken focus of much of the attention here.  FDA regulators are moving towards creating a new standard to be applied across the industry that will supersede the self-regulatory efforts of industry up until this point, welcome news to consumers – but this was about the point at which welcome news ended.

    Evidence is Beyond Compelling


    Major research presented at the conference following Sebelius did not really uncover anything new.     It reinforced findings that TV advertising is directly causing overeating with a variety of interesting approaches taken by the research teams around the world to prove this point.  Some looked at the ads themselves on TV and how that influenced behavior while other approaches studied the psychological effects of newer ‘advergames’ on the internet children play.  Whatever the method, the message was clear: all this advertising was having a major effect on children’s eating behaviors, pushing them to eat more often and lower quality foods then they would otherwise.

    Childhood Obesity Up Close

    Still, this part of the FTC conference actually had a good speed to it and they quickly went through all the research.  In many ways, the research phase of the conference felt like a warm-up and, if you think about it, this makes sense.  The whole premise of the FTC is to protect the consumer so the mere fact they are holding a conference on the subject assumes there is a serious problem with the way foods are being marketed to children.

    What was disappointing, however, was the way all this information was presented – in FTC’s own building! – with very little commitment to action.  We understand the desire to present the information but if the FTC, a consumer protection agency, calls a conference on a subject, there must a scientific consensus that action needs to be taken.  We found this portion of the conference incredibly counterproductive.  You just don’t get a many opportunities with the best minds in one room – why waste it presenting information everyone was already familiar with, especially with no commitment to action following those presentations?

    How Free is this Speech?

    The High Court, by laura padgett on flickr

    Getting more to the actual issues at hand was the second phase of the conference.  The FTC called together some very bright lawyers to interpret how the 1st amendment applies to childhood advertising by food companies. What may at first sound trivial – how free speech applies to advertisements – is, in fact, crucial to understanding what regulators can legally do in this situation to limit these destructive ads.  The short answer: very little.

    The core of the problem is that the Supreme Court views corporations as people, dating from a distant 1880s decision that created the idea of ‘corporate personhood’.  With that view, the Supreme Court has routinely held the view that corporations are fully entitled to the same free speech rights anyone of us would have.  This softened a bit as it crystallized into a set of legal standards to see if the corporate speech qualifies for protection via a case in 1980s called Central Hudson. The four part test looks like this (notice how each step is interconnected):

    • (1) whether the speech at issue concerns lawful activity and is not misleading;
    • (2) whether the asserted government interest is substantial; and, if so,
    • (3) whether the regulation directly advances the governmental interest asserted; and
    • (4) whether it is not more extensive than is necessary to serve that interest.

    The Balancing Act

    Applying these standards has proven difficult.  The FTC’s ability to make industry wide advertising bans was stripped in the 1980s so individual legal action against each TV spot, referencing the above Central Hudson test, would be required.  Obviously, that avenue is nearly impossible, which makes the Congressional decision to tie the FTC’s hands an invitation for more of this behavior.  The situation is compounded by separate corporate speech cases that have been challenged against Central Hudson, thereby strengthening the original decision and how it might be used to defend against childhood obesity.

    With the idea that food industry “advocacy is not fraud,” Martin Redish, a professor of law at Northwestern University that has written more than ten books on the first amendment, shows, convincingly, that there is a defense for industry here hidden away here inside the First Amendment.

    His view is that corporate speech is a slippery slope, even with the Central Hudson 4 step tango. He takes a strict constructionist view of the first amendment here: the second any type of agency from the government makes the choice that certain types of communication from a ‘person’ can be regulated you undermine the entire basis of the first amendment – which is the free expression of ideas.

    Using Redish as a crutch, the following speaker Dan Jaffe, executive Vice President of Government Relations (read: lobbyist) for the Association of National Advertisers (ANA) threw his two cents into the mix, in a much less convincing package.  He presented his case on whether or not to ban childhood advertising and – surprise surprise! – he felt that the government should leave the whole thing alone because corporations are entitled to free speech, echoing Redish.

    Further, Jaffe reminded us, the prestigious Institute of Medicine evaluated the issue of obesity and “restricting free speech was not in their list of recommendations.”  The ANA itself has launched a bunch of initiatives to show they are trying to get their act together but the measure rang hollow, especially at conference that was specifically aimed at curtailing their very activities.  Jaffe immediately reminded us of an old saying from Mr. Upton Sinclair:  “It is difficult to get a man to understand something, when his salary depends upon his not understanding it.”  Enough said.

    Yet another view of the first amendment was presented by David Yosifon of Santa Clara University and I found his argument the most compelling on this panel.  He focused on the concept of power economics and the efficiency of the market – basically arguing that information is so overwhelming and so sneaky that it is not truly information being communicated in a just manner, effectively failing the first point of the central hudson test.  In essence, the consumer does not have the ability to do decide on the efficacy of the argument being made, especially since they are so young.  “Puffery” is name he gave to the practice of corporations sliding messages into advertisements and it seems apt to apply that here.

    The Long and Winding Road

    We can tell you this much from these speeches (which were excellent): Dr. Redish presented the first amendment as so flexible in regards to corporate personhood that it would not make sense for the FTC to repeat their defeat in the 1980s of trying to get childhood advertising banned.  If you go further into the issues presented here today, you get the overriding sense that the Supreme Court is forcing consumers to act on their own behalf.  This idea really does speak to the ideal of what America is about but its blind to the reality facing our society.

    When our youngest people are being assaulted by subliminal messages to eat, embedded in a distribution model that is almost invisible to them, the first amendment can not – and should not – apply.  Free speech is limited in many ways.  You can’t scream ‘fire’ in a theatre full of adults, why should you be able to whisper ‘eat Froot Loops’ into a kid’s head ten times a day?

    Everyone on either side of the issue clearly understood the connection between the way these ads aimed at children are literally targeting their subconscious behaviors, training them into obese eating machines before they even possess the ability to make conscious decisions.  How this could not be construed as violating one tenet of the Hudson test is beyond us.

    Time to Walk that Walk

    The practice is simply gross, there are no others words to describe it.  But shame doesnt get very far with multinational companies – and the FTC of all organizations should know  this.  The real emphasis seems like it should be put into creating a legal framework from which the FTC can actually create binding regulations to limit the practice, or at least rules on how as to not harm consumers.  As so often is the case, the buck really stops with Congress as they write the laws and would have to directly address corporate personhood or give the FTC back the industry-wide banning abilities it took from them in 1980.  The history is especially interesting:

    Seeing as this is not a legal blog, the details of how this would be implemented are outside our areas of expertise, but the continued use of the first amendment as a way to turn America’s youth into obese zombies should be off the table.  Even industry, with their feigned attempts at creating self-regulatory mechanisms, seems aware of the contradiction here.

    So, we left this conference, like so many others, wondering what the goal was.  Networking is admirable inside any industry but the FTC is a special unit of the US government tasked with protecting consumers.  They herded the best minds in the world into one room, where everyone is keenly aware of how these junk food ads are creating obese kids, and did nothing.  It would seem a far better use of everyone’s time would to bring these experts together to a multi-day conference where the end goal is produce a concrete way to eliminate these ads – one that involved the appropriate Congressional subcommittees who could act on the issue.  Nothing at this conference brought us any closer to that reality.

  • Understanding Our Bodies: The Role of Antioxidants

    Understanding Our Bodies: The Role of Antioxidants

    It seems like every day there’s a new super-food that is chock full of antioxidants and ready to cure everything from the flu to cancer. Antioxidants are touted as a nutritional panacea, but I would bet that few people really understand what antioxidants are, how they function in the body, and how including them in their diet makes an impact.

    These are the antioxidants you want – from flickr user crabchick

    Are antioxidants good for you? The short answer is yes, but buyer beware. Just because something is good for you doesn’t mean you should start taking a giant mega-dose of it. Antioxidants are great when the come from natural sources as a part of a healthy diet. But like everything else, a closer look at their physiological action explains why you can get too much of a good thing.

    It’s All About The ROS

    What are antioxidants? To answer that question, you have to understand reactive oxygen species, or ROS. And to do that, you have to understand how your cells produce energy. So here we go: a very quick overview of cellular energy metabolism.

    In human cells, like other eukaryotes (everybody but the bacteria), energy is made in a specialized cellular structures called mitochondria. Mitochondria are these strange, double-membraned organelles that are highly specialized – they contain their own DNA, make their own proteins, and are tightly regulated by the cell. Essentially, mitochondria are energy powerhouses, or the cell’s equivalent of a power plant. Below is a 3D view of the structure (thanks to T. G. Frey of San Diego State University):

    watch : http://www.sci.sdsu.edu/TFrey/?MitoMovies/CrisMitoER.mov

    Using a complex process, mitochondria take our fats, carbohydrates, and excess proteins and turn them into a four-carbon molecule called Acetyl CoA. This molecule goes through a series of reactions in what is called the Kreb’s Cycle which results in the creation of high-energy electrons taken from the bonds.

    These electrons are then passed down a chain of enzymes which use the energy they possess to create a proton (H+) gradient between the center of the mitochondria and the between-membrane space, eventually reducing oxygen into water (O2 –> H2O).

    It’s this proton gradient that is used to drive an enzyme called ATP synthase, which creates ATP, the functional energy molecule used by our cells.

    But the system isn’t perfect. Every once in awhile, instead of making harmless water, the chain makes unstable oxygen molecules, which are referred to as free radicals. These molecules are dangerous to the cell because they are highly reactive – in other words, they attack chemical bonds – hence their other name, reactive oxygen species (ROS). They can cause damage to DNA, enzymes, proteins and many of the other vital components of a healthy cell.

    Luckily, our bodies have innate mechanisms to deal with ROS, like the enzyme catalase which converts hydrogen peroxide (a kind of ROS) into water and oxygen. But as we age, our mitochondria get less and less efficient, producing more and more ROS. If too many ROS are produced and they overwhelm our innate damage repair mechanisms, our cells suffer, and either become non-functional or even cancerous.

    That’s where antioxidants come in. Antioxidants are compounds which react with free radicals and neutralize them, thus protecting our bodies from oxidative damage by ROS. They vary widely and are found in all kinds of foods we eat every day. Perhaps the most famous antioxidant foods are the colored berries like blueberries and raspberries, which are chock full of a antioxidants like Vitamin C and Vitamin E.

    So ROS are bad?

    Well… like everything else, it’s not quite that simple. Yes, reactive oxygen species can be very damaging. Some scientists finger them as the direct cause of aging, and because of the damage they can cause, they are thought to play a pivotal role in many diseases from Alzheimer’s to cancer. ROS production is increased in people who are overweight or obese, and is considered one of the reasons why weight gain is so damaging to the body.

    But many ignore the fact that ROS are a normal and regular part of cell metabolism. Even when we’re healthy, we boost the production of ROS when we exercise and when we eat. As it turns out, we need them. They are important in a number of cellular pathways, including those related to programmed cell death (apoptosis), as they are a direct measure of how much energy is being created by a cell at a given time. Increases in ROS may actually be beneficial at the right times.

    For example, one study found that if you up the ROS in mice being fed a high fat diet, you actually prevent them from becoming insulin resistant. Insulin resistance is the first step towards diabetes – it occurs when our bodies stop responding effectively to the insulin we release to store glucose uptake.

    Over time, eating too much (especially too much sugar) leads to a constantly high insulin levels, and our bodies simply become less sensitive to insulin. ROS, as the researchers explain, are key in insulin signaling, and without them, our cells can’t respond efficiently to insulin.

    “In the case of early type 2 diabetes and the development of insulin resistance, our studies suggest that antioxidants would be bad for you,” explains Tony Tiganis of Monash University in Australia.

    Furthermore, increases in ROS are pivotal in the heart’s ability to prevent damage during a heart attack. If you boost ROS signals before a heart attack, it allows the cells to precondition and prevents later damage from oxygen deprivation. This pathway, including ROS, are being evaluated as targets for therapeutics and pharmaceuticals to reduce or prevent heart damage.

    As with anything, ROS are healthy for you when they’re kept balanced by the body’s defensive enzymes and antioxidants. Natural, low-ish levels of ROS signaling, like that produced when you eat a good diet and exercise, is good for you. But get too much of a good thing – like when your body’s natural oxidation defenses break down – and it becomes a bad thing. Eating a variety of fruits and vegetables, packed with antioxidants, has been shown to improve the body’s ability to deal with ROS properly, improving all kinds of physiological parameters and aiding in the prevention or treatment of a wide variety of diseases.

    Should I take extra antioxidants?

    Increases in overall fruit and vegetable intake have shown to be great for our bodies, but this is likely due to the interplay between many different compounds. The jury is still out on whether supplementing your diet with specific antioxidants improves your health.


    Clinical trials have had remarkable trouble finding actual benefits from supplementing diets with individual or even combined antioxidants.     A vegetable or fruit is better for you because doesn’t just contain one or two antioxidants; it also contains a balance of vitamins, minerals and enzymes that are impossible to reproduce in pill form.

    And more importantly, you can over do it. The line between healthy and unhealthy blurs when it comes to dietary supplementation with excessive amounts of antioxidants. For example, you smokers out there might want to watch your beta-carotene intake. Beta-carotene is an antioxidant, found in many vegetables including kale and spinach, and researchers had hoped that supplementing the diets of smokers with it and another antioxidant, retinol, would help prevent lung cancer.

    But the reverse occurred – beta-carotene was found to actually increase the risk of lung cancer and death when taken as a supplement by those who were at high risk for the disease. Why it had this strong, negative effect is not fully understood, but it serves as a warning that over-supplementing isn’t a good idea.

    Similarly, a meta-analysis of clinical trials involving Vitamin E found that high doses – >400 IU a day – increased risk of mortality. It’s likely that in both these cases, the excessive levels of antioxidants actually prevented the ROS from doing their job as signaling molecules, screwing up cellular signaling pathways including those that lead to cell death. Cells that don’t die when they should are at high risk for becoming cancerous.

    You probably aren’t going to do yourself any damage by eating all the antioxidants you want – and, more likely, you’ll improve your diet. But don’t try and overdo it with pills. Cramming ten extra Vitamin C tablets isn’t going to do you any good. Antioxidants are better when they come straight from the source, as they exist in a form your body is prepared to use.

    Studies have shown supplements simply don’t cut it, and super pills don’t replace eating a healthy, balanced diet with at least five servings of fruits and veggies a day. And in some cases, antioxidant supplements increase the risk of cancers, like beta-carotene did for smokers, and can be particularly damaging for those already on certain drugs.

    If you really insist on taking supplement pills, be sure to talk to your doctor first and make sure what you’re taking is actually good for you and isn’t going to conflict with other medications. So-called nutritional supplements often tout amazing health benefits without any actual science to back them up.

    Previous posts in the Understanding Our Bodies series:

    References:

    1. Stadtman, E. (1992). Protein oxidation and aging Science, 257 (5074), 1220-1224 DOI: 10.1126/science.1355616
    2. Liu, J. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid Proceedings of the National Academy of Sciences, 99 (4), 2356-2361 DOI: 10.1073/pnas.261709299
    3. Zhang JW, Rubio V, Zheng S, & Shi ZZ (2009). Knockdown of OLA1, a regulator of oxidative stress response, inhibits motility and invasion of breast cancer cells. Journal of Zhejiang University. Science. B, 10 (11), 796-804 PMID: 19882753
    4. Rhee SG (2006). Cell signaling. H2O2, a necessary evil for cell signaling. Science (New York, N.Y.), 312 (5782), 1882-3 PMID: 16809515
    5. Loh, K., Deng, H., Fukushima, A., Cai, X., Boivin, B., Galic, S., Bruce, C., Shields, B., Skiba, B., & Ooms, L. (2009). Reactive Oxygen Species Enhance Insulin Sensitivity Cell Metabolism, 10 (4), 260-272 DOI: 10.1016/j.cmet.2009.08.009
    6. Vanden Hoek T, Becker LB, Shao ZH, Li CQ, & Schumacker PT (2000). Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion. Circulation research, 86 (5), 541-8 PMID: 10720416
    7. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, & Telser J (2007). Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry & cell biology, 39 (1), 44-84 PMID: 16978905
    8. Wallig MA, Heinz-Taheny KM, Epps DL, & Gossman T (2005). Synergy among phytochemicals within crucifers: does it translate into chemoprotection? The Journal of nutrition, 135 (12 Suppl) PMID: 16317157
    9. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, Valanis B, & Williams JH Jr (2004). The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. Journal of the National Cancer Institute, 96 (23), 1743-50 PMID: 15572756
    10. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, & Guallar E (2005). Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of internal medicine, 142 (1), 37-46 PMID: 15537682
    11. Rodrigues MJ, Bouyon A, & Alexandre J (2009). [Role of antioxidant complements and supplements in oncology in addition to an equilibrate regimen: a systematic review] Bulletin du cancer, 96 (6), 677-84 PMID: 19493854
  • Food System 2.0: Can New Approaches Make Local Food Happen?

    Food System 2.0: Can New Approaches Make Local Food Happen?

    What is the price of food? $3.99 for a gallon of milk? $0.99 for an energy bar? Complex market and policy forces make those prices. Its a process that starts far from the point of sale.

    Centralizing our food into fast food chains and supermarkets causes the farms that feed the system to scale up into mega-sized operations. The idyllic, diverse farms of American lore were long ago converted into monocrop fields of staple grains, hog farms with hundreds of thousands of head and distribution centers bigger than football fields.

    A moment at the supermarket… thanks to flickr user Fazen

    In economic terms, food has simply migrated to areas with the a comparative advantage in production. California, for example, now grows over 50% of all the vegetables in the entire country – simply because they have a 12 month growing season. But how do you make food scale back to something more reasonable, a new system in which communities connect with the food being grown there? Is it even possible, nay desirable?

    We saw a couple examples of new approaches to these questions in the San Francisco area during our Tour of America recently. One deals with technology while the other with community. Both are necessary components in what should become Food System 2.0.

    From Ideals to Reality

    On a sunny afternoon in San Francisco, we sat down with Melanie Cheng, founder of Farmsreach.com. FarmsReach does what it says: it puts farms directly within reach of their marketplace. But don’t think of the service as a digital farmers market, as we made the mistake of doing. The genius of the system comes in their measured approach to tackling the economics of local food.

    Cheng started out as a technical writer, working with Silicon Valley giant Cisco. This technical background came in handy as she began to turn her attention to food. The environmental impact of agriculture was her first focus, which culminated in the non-profit OMorganics.

    She quickly realized the main obstacle in the sustainable agriculture world was a lack of information and marketplace – causing a shift from environmental issues into more broadly seeing food access as a uniting factor. This revelation began to shift Om Organics from information to technology, out of the non-profit sphere into what we know today as FarmsReach.com.

    Their first prototype was to connect restaurant chefs with farmers through farm co-ops and aggregators – a focus that proved too time consuming to be profitable. The core need to connect farms with commercial buyers still remained however, so with their first public release FarmsReach.com, the focus was helping farms sell directly to buyers. Cheng used an interesting approach to get these small farms to scale up to restaurant sizes: combine them.

    What Farms Reach Looks Like

    It was with larger restaurant accounts that could do multiple orders at once that Farmsreach.com was born. The service aggregates sellers – in this case farmers – so restauranteurs and institutional food buyers have an easier way to interface directly with sustainable and local growers.

    Cheng’s team has tested the current platform in seven different regions, trying to slowly build out new features the community requests, like ratings for participants and inventory management for restaurants. The platform is young having only formally launched earlier this year, but it was our impression that the combination of a great idea, a strong team and patient investors will eventually make FarmsReach a big commercial component of a burgeoning new food system.

    The Smaller Side of Food

    But what if you aren’t a large restaurant? How do you get access to better food? Sara Weihmann, co-founder and director of All Edibles sees edible landscaping as filling that important gap in the current food system. After completing a Green MBA in 2006, Weihmann looked at various environmental and social justice issues like green building and biodiesel production before the food world came calling.

    Weihmann and her co-workers at All Edibles add edible plants to existing homes in the form of pleasant looking landscaping mostly in the ‘East Bay’ area of the San Francisco region, Berkeley and Oakland. They help homeowners connect with their food by teaching seasonal eating, planting in cycles to ensure constant food production and generally educating their customers on how to grow food.

    An example of an All Edibles Installation in the Bay Area

    The real take home message with their services is turning consumers into producers, mostly through educating clients on the processes that make local food a superior choice to conventional supermarkets. Improved local environments, food quality and convenience become selling points over the predictability of supermarkets after the clients see their food coming out of their own yards, Weihmann explained. Her goal is to eventually transform her work into a curriculum for schools and nursing homes, educating those that usually have the least connection with food – and the most time on their hands to participate.

    The Economic Side of Food

    These diverse food system interventions are merely novel at this time, experiments into a new method of food distribution that aims beyond the bottom line. No new system will succeed without a profitable economic base.

    Food Income Chart – click for detail

    Our specialized system has driven the costs of food down to levels that are the envy of the world – which is hard to argue – or compete – against. Americans spend only about 10-12% of their income on food, according to the Bureau of Labor Statistics (see this NYTimes infographic to better understand). That’s one of the lowest percentages in the world. The foods that make up that chunk of the economy are heavily influenced by subsidies from the Farm Bill, a sprawling piece of legislation that incentivizes certain crops. For example, corn farmers have received a staggering $56 billion in subsidies over the last 10 years.

    Farms Reach and All Edibles are attempts to change that paradigm. They are trying to circumvent the traditional food system by introducing market forces and genuine community elements to what has long been a faceless production. Remedying the larger policy apparatus around food will have to follow these trailblazing attempts to augment the system but there is another tangential issue at hand here which could change the debate – health care.

    From Reaction to Prevention

    As the US contemplates how to remake the health care system, the Congressional Budgeting Office reminds us that America already spends 16% of its GDP on healthcare, by far the highest percentage in the world.  Using nutrition and novel market attempts like Farms Reach and All Edible to get the right foods into the right hands could be an important part of getting Americans to put more money into the food side of the equation – and less into fixing preventable diseases later on. Preventative medicine interventions have long been ignored, said Patricia Lebensohn, Associate Professor of Clinical Family and Community Medicine at The University of Arizona’s Integrative Medicine in Residency Program.

    Mediterranean Watermelon Salad, by the Foodista Blog

    Our current food and health states in America are efficient monetarily but woefully inefficient in other less measurable ways. Lebensohn spoke to the ways in which the Tucson-based interactive program gets front line medical practitioners to consider the person on more holistic level – and a big component of that is nutrition intervention. University of Arizona preaches a Mediterranean diet – heavy in whole grains, vegetables and fish – as a good approach for most practitioners. Frequently, the same residents receive training in how to use diet as a tool to make the body heal itself, added Lebensohn.

    Connecting food to health is a major aim of the University’s program – but it goes hand in hand with other environmental, social and moral aspects of the food system that need updating. Approaching this problem from both the educational/government side like Lebensohn and the Weil Center while using new ventures from the likes of Cheng and Weihmann are just the kind of multi-faceted, entrepreneurial approaches to these large questions that are uniquely American.

    Remember, it was only about 10,000 short years ago that we even discovered farming in the first place. It shouldn’t take that long to integrate these methods into a food system that nourishes us into the next century – and the one after that.

  • When You Should Eat

    When You Should Eat

    More often than not, dieters focus exclusively on what’s going into their bodies. They cut out food groups, add food groups, count calories and create meal plans. But research has found out that while what you eat does matter, when you eat has a big impact, too. According to new research from Northwestern University published in the journal Obesity, eating at night can increase weight gain by more than 25%!

    The Background

    Watch the clock when you are eating, thanks Steven Depolo

    Our bodies have an innate timing system called the “Circadian Rhythm” or “Circadian Clock.” Hormones and chemical releases tend to tell us when we’re supposed to wake up, when to sleep, and a variety of other day-to-day activities. Some of these can be altered with consistent changes to daily patterns – getting up a few hours earlier, for example, can affect when your body decides it’s time to get up. But others are dependent on external influences and are much harder to shift. It’s been suggested for a long time that our bodies internal clock has a big effect on our weight loss or gain.

    Meals eaten in the morning, for example, have different hormonal effects than the same meals eaten in the afternoon. One of the major factors seems to be cortisol levels, which, after not eating all night long, are much lower in the AM.

    When dieting, we’re often warned not to eat late at night. This conventional wisdom, however, has generally had little support scientifically. No studies have shown whether the daily effects we see are absolute or simply due to current patterns. In other words, if a person were to change when they normally eat, it’s possible that the effects we see from morning v. afternoon meals would change, too. Specifically, if one were to eat at night, it’s suggested that the increased cortisol levels would negate the effects seen by other meal-timing studies.

    So where does the “don’t eat at night” wisdom come from? Well, mostly, scientists have shown that people tend to eat more when they snack later, thus increasing their overall calorie intake and subsequent weight gain.

    But Northwestern University researchers started to think there was more to it. They noticed that late-night shift workers who end up regularly eating at odd hours of the day tended to weigh more than their daytime shift counterparts. Were they really just eating more than the daytime shifts, or did the timing of their meals have an effect on their weight?

    Northwestern University researchers hypothesized that there was more going on. They wanted to know if our body’s daily rhythms have an impact on how food is processed. So, they designed a study with mice to determine if eating at night has an affect on weight gain.

    The Study

    Watch those midnight snacks, or fat mouse disease might strike.

    To determine how our circadian clock affects weight gain, the researchers took mice and fed them a high fat diet. They split the mice into two groups, allowing both groups of mice to eat as much as they wanted for 12 hours, and recorded how much they ate and their activity levels.

    The only difference between the groups was that one group was fed during the normal waking hours, the other, during the night. They gave each group the exact same food with the exact same nutritional values and fat content, to see if timing alone affected weight gain. After six weeks – plenty of time for their mice bodies to adjust to the patterns – the results were staggering.

    Both groups ate the same amount of food and had the same levels of activity. And, because they had such a high-fat diet, both groups gained weight. Those fed during the day increased their body mass by an average of 20%. But the nighttime fed mice gained a lot more than that, increasing their body mass by an average of 48%. That’s 28% more weight gain just by eating at night instead of during the day!

    The researchers are following up by looking into the molecular mechanisms behind this increased weight gain. Their hunch is that the few hormones that are on strict circadian clocks (ones that don’t change even when you stay up all night repeatedly, for example) might influence how fat is processed in the body.

    The Take Home Message

    Just like you have to think about your activity levels when working towards weight loss, you have to consider when you eat as much as what you eat. And not eating at night is just one facet of this: how many meals a day, what you eat at which meals, and when you eat those meals during the day also have impacts on the overall success of the diet. Cutting calories isn’t everything!

    Arble, D., Bass, J., Laposky, A., Vitaterna, M., & Turek, F. (2009). Circadian Timing of Food Intake Contributes to Weight Gain Obesity, 17 (11), 2100-2102 DOI: 10.1038/oby.2009.264

  • Plastic Troubles: Brominated Flame Retardants (PBDEs)

    Plastic Troubles: Brominated Flame Retardants (PBDEs)

    In general, we think of plastics as non-flammable. Sure, the pyromaniacs among us have put a lighter to picnic cutlery to see what happens, but for the most part we know they melt, not burn, and are not exactly the best source of tinder or firewood.

    But that’s not actually true. Almost all pure plastics are inherently flammable. When exposed to heat and flame, the polymers in plastics split into smaller, more volatile pieces. As oxygen reacts with these new compounds, more heat is produced, further ensuring a combustion reaction. This chain reaction continues until all of the plastic is broken down.

    Even with flame retardants, plastics can burn – Pic by tronics on flickr

    On top of the actual flame, burning of plastics can also be dangerous as it can create toxic gasses from the chemical components. Thus, as you can imagine, flammability is a huge problem for plastics used anywhere where heat might occur – near currents in electronics, in the kitchen, even furniture. The only thing that keeps most plastics from going up in smoke are the flame retardants mixed into the plastics themselves.

    Keeping the Flame at Bay

    Flame retardants act to stop the chain reaction that heat and flame cause, either slowing or preventing the spread of the fire all together. Almost all plastics that we come in contact with have added flame retardants in them to prevent ignition. One of the most popular types of compounds used in plastics are brominated flame retardants. As the name suggests, they all contain bromine. These are applied to 2.5 million tons of plastic polymers annually. One particular group, polybrominated diphenyl ethers (PDBEs), are used so much that the world consumes 40,000 metric tons of it every year, with 34,000 or so of those being manufactured in North America.

    The variety of products that use brominated flame retardants is astounding. They’re in:

    • almost every piece of electronics you buy from TVs to computers
    • carpets
    • paints
    • kitchen appliances
    • upholstery
    • car parts
    • building materials

    They’re so well used by the industry because they work great. Not only do they prevent ignition, they slow the spread of fire, giving anyone near it precious extra seconds to escape.

    Of course, like the other compounds added to plastics, brominated flame retardants and PDBEs don’t all stay neatly wrapped up in the plastics they’re added to. They, like BPA and phthalates we covered earlier, tend to leech out into the environment, which is where the danger sets in.

    What Are PBDEs? And why are low levels potentially dangerous?

    PBDE, in its chemical glory

    With over 209 different compounds used, polybrominated diphenyl ethers (PDBEs) are the largest group of brominated flame retardants used in plastics. They’re split into two types: “lower brominated,” or containing less than 5 bromines, or “high brominated,” with more than five. The big concern is with the more popular lower brominated PBDEs, as they are known to bioaccumulate.

    Most of the time, we worry about acute exposures. That’s when the body has a sudden, high dose of something bad for it, to the point that it can’t deal. For example, if you chug a 24 pack of Bud Light in less than an hour, you’ll probably get acute alcohol exposure and be rushed to the hospital. But, odds are that if you are treated fast enough and have your stomach pumped, you’ll be fine in a few days. Your body processes alcohol fairly quickly – though it might not seem like it when we’re horribly hungover. In that sense, most people don’t have to worry about PBDEs. While common, your daily exposure is pretty low, so unless you go chugging chemicals at a plastics plant you’re not likely to suffer from acute exposure to PBDEs.

    Bioaccumulation is Different

    Bioaccumulation refers to the amount of a substance, usually toxic, that occurs in an organism over a much greater period of time. It occurs when a substance is absorbed or stored at a faster rate than it is lost, causing it to ‘accumulate’ in the body. When bioaccumulation occurs, smaller environmental levels can have a much larger impact.

    Imagine if every time you had a drink, your body simply couldn’t get rid of the alcohol in the beer, and instead, it lingered in your tissues. You could have one drink a week, but still within a few weeks you’d be drunk all the time. That’s what happens with PBDEs – they sit in your body, and don’t go anywhere. Unlike BPA where you have to have a threshold daily dose for effects to occur, PBDEs can be toxic at extraordinary low daily doses – it just takes longer for the effects to show.

     

    If beer bioaccumulated like PBDEs, we’d all be in big trouble, thanks to flickr user tambako for the stunning shot

    PBDEs bioaccumulate in blood, breast milk, and fatty tissues. Because they’re so common, the average person is exposed to PDBEs from all kinds of places. You inhale them as they evaporate from building materials in your home and eat them when they leech from your tupperware. For that matter, it’s not just the plastics in your life you have to worry about.

    Humans aren’t the only species that PDBEs bioaccumulate in, and as they become more prevalent in the environment, they become more prevalent in our foods. Significant concentrations have been found in popular foods like salmon, ground beef, butter and cheese. The higher up an animal is on the food chain, the more of a bioaccumulating compound it’s likely to have. And that’s not good news for us people, who reside squarely at the top.

    There’s reason to fret about PBDEs – their close cousins have already been banned as health risks. You might have heard of them – polychlorinated biphenyls, or PCBs. They, too, were used as flame retardants, as well as other things, starting in the early 20th century.

    More deformed fish will pop up unless we get rid of these chemicals

    It became clear, though, by the 1970s that PCBs were seriously dangerous organic pollutants, causing birth defects, impairing brain and memory functions, and increasing the risk of some forms of cancers. But that was not before General Electric released up to 1,300,000 lbs of PCBs into the Hudson River, prompting the New York State Department of Environmental Conservation to ban all fishing in the upper Hudson due to unacceptably high health risks to anyone who consumed their catch. And, unfortunately, GE was not alone. The effects of PCB use still linger today, especially in aquatic animals. And PBDEs are already accumulating – research has shown that PBDEs are at least as prevalent as PCBs in Lake Michigan salmon, for example.

    Effects of PDBEs

     

    Like with all plastic chemicals, kids are at the highest risk (sukanto_debnath credit)

    In the United States, PBDE concentrations are rising, especially in children. Toddlers and preschoolers have 3 times higher blood concentrations of flame retardants than their mothers – an average of 62 parts per billion. And adults aren’t off the hook. A study in Spain in 2003 found that adult men there were chowing down 97 nanograms/day in their meals. No study has looked at the daily intake in the United States, although previous studies have shown that Americans rank among the highest in bodily concentrations of PBDEs. U.S. mothers, for example, had concentrations of PBDEs 75 times higher than the average levels in Europe. And no one, anywhere, has studied how much of what we ingest stays in our bodies, accumulating in our fatty tissues.

    While “parts per billion” and “nanograms” might sound like a very small amount, it’s still dangerous, especially for kids. Even a single, low dose given to developing mice caused permanent behavioral and neurological changes. Other studies have found that over time, PBDEs alter thyroid function, disrupt brain development, drive cells towards cancerous activity and even cause hyperactivity.

    Unfortunately, the study of PBDEs is still fairly new. It wasn’t until after the fiasco with PCBs that PBDEs were phased into use, and research has not had the time to fully study the long-term effects of these chemicals. What we have seen, however, isn’t looking good. Blood concentrations are quickly approaching the EPA’s magical “safety limit” for people, and research continues to show lower and lower doses having detrimental effects on animals.

    Where We Go From Here

    The good news is governments are taking notice of PBDE and the dangers involved. In the 1990s, the European Union began replacing brominated flame retardants, and levels in breast milk there have decreased in response. They one-upped themselves in 2006 by flat out banning the use of certain PBDEs in electronics. In the U.S., states like California, Hawaii, New York, Michigan and Maine have already passed PBDE banning legislation, and other states are following. But the federal government has yet to listen to the complaints against PBDEs or take any action against them.

    The bad news is, if you live where it isn’t banned, there’s not much you can do to avoid it. Even if you do live where it’s no longer added, older furniture and plastics will still contain PBDEs. The best you can do is support organizations like Greenpeace which seek to see PBDEs banned entirely or petition your local politicians to make it an issue. There are alternatives to brominated flame retardants, and new technology continues to find ways around using harsh chemicals to prevent fires. We should to our best to remind industrial companies that being cheaper doesn’t make a chemical better – we need to find new ways to make what we need without poisoning our children and environment in the process.

  • Plastic Troubles: Phthalates and Plasticizers

    Plastic Troubles: Phthalates and Plasticizers

    Plastic is a buzzword lately but mostly for the wrong reasons.  Medical studies have lined up against the ubiquitous substance and the seas have filled with the jetsam and flotsam of our plastic society.  Yet, if there was one compound responsible for this situation more than any other, phthalates might just wear the crown.

    Chemistry

    Phthalates make plastic, well, plasticy. Many consumer goods are made up of very hard plastic compounds that do not allow finished products to move as required, like the PVC piping you find in many modern homes or the casing to your internet router.  And with a little phthalate magic added into the chemical mix, those PVC molecules that were once rigid in the pipes of your home are now free to form the flowing plastic carpet you often find beneath your feet.

    Phthalates keep Fish Oil Omega3’s in place – thanks to flickr user Deco Fernandes

    In fact, these molecules are so unique and helpful, they have found their way into almost everything we use.  Personal care products, mechanical lubricants, paints, modeling clay, shower curtains, food containers and wrappers, even children’s toys all have some phthalates mixed in.  Health care items like the coatings of prescription pills and supplements are also guilty.

    The magic of phthalates is that they allow the larger polymer plastic molecules to slide against one another more easily.  Phthalates move so well because they do not bond directly those large molecules, leaving them roam about in some cases.  Roaming phthalates leech away from their plastic motherships, leading to that new car smell, paint fumes and the heavy offgausing associated with new flooring.

    Health Risk Debate

    With the volume of phthalate in existence, our exposure to such materials is obviously high. Our main exposure is from what we eat but inhalation and absorption through the skin are also important factors.  Some scientists suggest that children are so regularly exposed to the plastic that they contain levels up to 20X what is known to be safe [1].  Part of the reason so little has been done about phthalates is that no one is perfectly sure what ‘safe’ really is.  So, the real debate with phthalates at this point has to do with quantity required to cause damage.

    Suggested exposures depend heavily on body weight and stage of life.  On study gave a rough estimate 5-20 micrograms of phthalates per kilogram of body weight, with higher exposures in younger populations [2].  Other studies suggest that we really aren’t quite sure what the exposure levels are, and consequently all of this needs more study [3].  We do know that phthalates have been shown to cross the placenta and transfer from mother to fetus and such exposure has been linked to risk factors and the inital stages of prostate cancer and to changes in emotional stability as adults, all things we could do without.

     

    Newborns are at the greatest risk, thanks to flickr user michelleannb

    Scientists classify phthalates as definite endocrine disruptors, a class of chemicals that throws off the body’s hormone signaling system.  Studies have shown high doses can cause birth defects in rats and even deformities in people.  Phthalates in particular are singled out from other plastics as a very possible epidemiological reason for the lower sperm counts seen across men in the Western world.

    Such bold claims come from correlations found between phthalate exposure and young boys with shortened “anogenital distance”, decreased penis size and improperly descended testicles [4], all major public health issues facing 21st century policy makers.  Prenatal exposure was also shown to negatively effect reproductive development in young boys.

    Youngest at the Greatest Risk

    But of any one study, Pediatrics really turned the heat up on phthalates back in early 2008 when they reported that 81% of all infants had significant phthalate exposure from simple household items like shampoos, lotions and powders [5].  Most troublesome was the way in which researchers deduced how young infants might have the highest exposure: by simply being kids.  From the study (-ed emphasis mine):

    Children have unique development and behavior that may predispose them to higher exposure susceptibility. When children are born, they immediately develop hand-to-mouth behaviors. They cannot move on their own and are therefore exposed predominantly to ambient air exposures, oral ingestion of breast milk/formula, and [skin] exposure to specific infant care products. As infants develop, they begin to move around, crawl, and have increased hand-to-mouth behaviors with the potential for increased exposure to phthalate sources in the environment.  But its not just children who have to worry, there is concern with adults too as phthalates have been linked to cancerous activity in adult cells.

    Since this publication, the EU and the state of California have effectively banned many phthalates from the consumer market, with California more conservatively banning them from toys and children’s products.  These bans have been especially contentious because unsafe exposure levels remain unknown and, more importantly, the size of the industry in question.

    The Political Dimension

    Despite growing concerns and widespread exposure, phthalate exposure continues almost completely unabated in the United States.  One of the cardinal organizations responsible for this is the American Chemistry Council (ACC).  This group’s name spoofs the largest and arguably most respected scientific organization in the world – the American Chemical Society (ACS) – but it obeys a very different master: corporations.

    The ACC represents all of the plastic companies and it obviously disagrees that phthalates cause problems.  They have been way out in front of this debate, publishing smears against phthalate detractors as recently as 2005 in prestigious medical journals.  They have even built a special website just for phthalates – http://www.americanchemistry.com/s_phthalate/ – and convened a “The Phthalate Esters Panel” to examine the facts through the warped lens of plastic manufacturers.

    The ACC does show that a wide range of products depend upon phthalates, from vinyl siding to medical devices and raincoats.  Other important uses like duct tape and protection films for food products have all benefited society.  But the ACC stance ignores scientific progress being made by their own members.

    Plastics without harmful phthalates have already been developed and deployed by major chemical companies like Dupont, with high customer satisfaction in some of the most demanding industrial environments.  Phthalate-free plastic welding is now also possible.  So it’s clear the innovations to move past phthalates are here today, giving manufacturers a bridge into the future of safer plastics from previous technologies like PVC.  What lacks are proper market forces or government regulation in the US to make the change occur.

    Steps To Take

    Here are some of the most basic steps you can take to protect yourself from this plastic:

    • -Let new carpeting/vinyl flooring off-gas while you are not present
    • -If painting, use proper ventilation to avoid excessive phthalate exposure
    • -Buy new electronic items that are RoHS compliant (a European standard that bans some phthalates)
    • -Buy consumer products in steel/glass when possible
    • -Purchase newer toys for kids, as many companies must comply with California’s ban on phthalates

    Small consumer purchases add up, so take account of what you are buying and try to avoid bendable plastics when you can.

  • Plastic Troubles: Bisphenol A

    Plastic Troubles: Bisphenol A

    It’s more than impressive to think about how pervasive plastic use has become. Despite only being around for the past century or so, plastics have become staple in every day life. From grocery bags to drinking bottles, IV bags to the teflon on non-stick pans, plastics really do make everything possible. They’re incredibly versatile: the final product can very in hardness, be shaped in almost any way imaginable, and is chemically inert, all for a bargain basement price. Really, it’s a magical substance.

    Its everywhere…

    Unfortunately, the very properties which make it so useful in so many industries are the same properties which make it one of the worst physical pollutant in the world. Despite recycling efforts, a large amount of plastic ends up in garbage cans (if we’re lucky) or littering the environment. Since the 1950s, one billion tons of plastic has been discarded by people. The ecological impact of all this plastic is devastating. Plastics make up at least 2/3 of marine litter, killing animals of all shapes and sizes. It takes over 450 years for a plastic bottle to degrade – that’s at least twice as long as it takes for an aluminum can to dissolve. And if that’s not bad enough, the forms of plastic that do degrade faster are even worse. Polystyrene – better know by the brand name “Styrofoam” – has been shown to degrade easily in seawater, but it leaves behind potentially damaging styrene molecules.

    But this isn’t an article about the ecological impact of plastics – there’s enough on that for an entire book. The key question isn’t how does it affect the environment, it’s how does it affect us.

    Plastic Chemistry 101

    Plastics are very complex compounds chemically. They are made from combining various carbon-based compounds, called “monomers,” to create long chains, called “polymers.” The most common forms of plastic used are polyethylene, polypropylene and polystyrene. Their names explain what compounds are used to create them – polyethylene is made from strings of elthylene, polypropylene from strings of propylene, and polystyrene from strings of styrene. Another well-known plastic is polyvinyl chloride, better known as PVC. Another kind of plastic, polycarbonate, is made from bisphenol A (BPA), and is used extensively in our households in items like bottles, plastic glasses, tupperwares, even DVDs and CDs. There are actually hundreds of different types of plastic, all made from different carbon-based monomers. The different compounds lead to different properties, including different levels of hardness, flexibility, and heat resistance.

    PVC Pipe, one of the most familiar forms of the common plastic

    But there’s a lot more that goes into plastics than just the monomers. Other compounds can be added to further change the textural properties of the plastic. PVC, for example, often has phthalaes added to it to make it less brittle. These compounds are referred to as “plasticizers,” as they add to the fluidity of plastics. Some plasticizers eventually evaporate from the plastics they’re put into – for example, the “new car smell” we associate with a brand new Mercedes is caused mostly by trimelliate plasticizers evaporating from the car’s interior. Others leech out of plastics as they degrade or are exposed to extreme conditions, like the heat in microwave ovens. Bisphenol A is added to certain PVC to make it harder, and other compounds, like brominated flame retardants, make plastics less vulnerable to heat.

    Luckily for us, most pure plastics that are free of such additives are fairly harmless. They are ecologically devastating because they take forever to degrade and ensnare marine and terrestrial animals, but as far as human use goes, they’re non-toxic. Unfortunately, most plastics we use aren’t pure. And even still, the compounds that make up pure plastics can be toxic, as the much more toxic, single monomers can be trapped in the plastic-making process only to be released later into our foods.

    So what’s the harm, exactly?

    What exactly do the chemicals in plastics do to the human body? A lot. And it depends on the compound. I’m going to dive into some of the big players and why you should know about them. First up is the one you’ve probably heard the most about: Bisphenol A, or BPA.

    Bisphenol A

    If you’ve paid attention to the news in the past year, you’ve probably heard a lot of talk about Bisphenol A. Like I mentioned before, it’s a monomer used to create polycarbonate plastics, labeled type 7, and also as a plasticizer in type 3 PVC plastics. It can leech out of either kind into food and water placed in contact with them.

    Plastic ‘resin’ code #7

    BPA is what is called an “endocrine disruptor“. Our endocrine system is the system of signals and hormones which constantly communicate information between cells. The problem with BPA is that it looks similar enough to estrogen that our bodies can’t really tell the difference. Because estrogen is such an important hormone in our bodies (in men as well as women, by the way), the potential affects of BPA on our bodies are severe and range widely.

    The first problem is that, so far, we’re not really sure how much BPA it takes to have a negative effect on our bodies, especially over a lifetime. It’s clear that a high, acute dose is bad, but where the bottom threshold is for humans is unclear. It wasn’t until 1997 that low-dose effects on laboratory animals were reported, though since then a variety of studies have used animal models to warn of the dangers of BPA.

    In animals like mice and rate, doses as low as 0.025 µg/kg/day can causes permanent changes to the genital tract and predispose breast cells to cancerous activity. Between 1 and 30 µg/kg/day can lead to long-term reproductive changes like earlier puberty and longer periods, decline in testicular testosterone, and prostate cell changes indicative of cancer, as well as behavioral effects like decreased maternal instincts and even reversed sex roles. Basically, BPA exposure can affect almost every system in our bodies, particularly those impacted by reproductive hormones.

    Older polycarbonate bottles all contain BPA, thanks flickr user vitameatavegalynn

    Think of anything that makes you manly or womanly – the shape of your body, your muscle mass, neurological systems – all are vulnerable to BPA’s toxic effects. Over 100 studies have been published which reveal different toxic impacts of BPA. The question isn’t “is it harmful,” it’s how harmful, and more specifically, at what dose.

    After all, anything can be toxic when in excess. You can even die from drinking too much water. The big question now among scientists is what level of exposure to Bisphenol A is low enough that it won’t cause major, negative side effects in most people. They also are looking into how much BPA we get exposed to and from where. What they’ve found is that BPA exposure is particularly high in infants, when, of course, it has the most side effects. Developing people and animals are much more strongly affected by hormone levels and disruptors like BPA which mimic those hormones in our bodies. The younger the person, the more of an effect a lower dose of BPA has on them – which is bad news for pregnant moms and newborn infants. Levels that are safe for adults are likely to be unsafe for them. But, to date, no study has looked specifically at the effects of different doses of BPA on in-utero or newborn infant biology.

    Exposure and Effects Still a Mystery

    So what, you ask, is our daily exposure anyway? Well, we’re not entirely sure. Studies have found that infants can consume up to 13 µg/kg/day when fed formula from polycarbonate bottles. Remember – that’s a dose high enough to cause serious reproductive changes in animal models. Adults can get similar levels of BPA exposure from single servings of canned goods (they use a plastic lining to protect the metal) and some from plastic containers, particularly those that are warmed up in the microwave or run through the dishwasher. The EPA has said that 50 µg/kg/day is normal and safe, but recent studies in our closest relatives have shown that level causes adverse neurological effects, even in adults. And even worse, scientists have found that monkeys given 8 times that dose – 400 µg/kg/day – have blood concentrations lower than the average human being. It’s likely, therefore, that we’re getting a lot more BPA than we think, and its probably worse for us than we thought.

    The first study of BPA’s effects on humans wasn’t published until September 2008. It looked at urine BPA levels in around 1,500 people to see if they correlated with disease. The researchers found that increased BPA levels were significantly associated with heart disease, diabetes, and high levels of certain liver enzymes. They concluded that “higher BPA exposure, reflected in higher urinary concentrations of BPA, may be associated with avoidable morbidity in the community-dwelling adult population.”  Many researchers claim we have known about this problem for far longer:

    Despite the overwhelming evidence of the dangers of BPA, the FDA recently announced that it still deems the compound “safe.” This preliminary decision was attacked by scientists and consumer groups who said the FDA was being biased towards the industry and not taking into account the science and the safety of the American Public. Canadian officials have already banned BPA use in baby bottles, finding that levels were simply too close to unsafe for formula fed infants, a decision which lead to many leading companies like WalMart and Toys R Us to stop selling them in Canada and the U.S. In June 2009, the FDA decided to “reconsider” its assessment of BPA safety levels, though a new finding has yet to be announced.  Rumor has it that FDA’s next decision on BPA should come down the pipe in late November.

    What To Do:

    In the end, my recommendation is to steer clear of bisphenol A-containing plastics as much as possible, especially when it comes to your kids. Here is a list of easy ways you can avoid BPA:

    • Be wary of all plastics labeled type 7
    • Absolutely, positively, do not buy polycarbonate baby bottles
    • Keep baby from putting hard plastics (like toys) in their mouths
    • Replace older polycarbonate ‘Nalgene’-type water bottles with stainless steel bottles
    • Replace canned foods, especially acid rich tomatoes, with those bought in glass
    • Microwave your food in glass or ceramic containers instead of plastic ones like tupperware
    • Use metal colanders in place of harder plastic ones for straining boiling water
    • Hand-wash hard plastic kitchen cups and utensils in place of hot dishwasher cleaning

    Sadly, BPA is only one of many toxic chemicals that can leech out of plastics. Next, I’ll tell you all about brominated flame retardants, called PBDEs, which unlike BPA, are found in almost every form of plastic.

  • Understanding Our Bodies: Leptin (The Fullness Hormone)

    Understanding Our Bodies: Leptin (The Fullness Hormone)

    Time and time again, I tell you guys that the best way to stay healthy is to stay informed. Read labels, I say. Know what you’re eating. Know what you’re not eating. Know this, know that, etc and make informed decisions. Well, part of making informed decisions is understanding how your body works. And for that reason, I’ve decided to dive into a bit of physiology.

    Even informed consumers tend to know very little about how their appetites actually work. What makes you hungry or full? Why do some foods fill us up more than others? What exactly is going on in our bodies, anyway?

    I figured you just might want to know. So here is part one of a new series I call “Understanding Our Bodies” – nutrition based on how our bodies work. And to kick it off is a little explanation of the fullness hormone: Leptin.

    What is Leptin?

    Leptin is a hormone that is tied closely to regulating energy intake and expenditure, including appetite, metabolism and hunger. It is the single most important hormone when it comes to understanding why we feel hungry or full. When present in high levels, it signals to our brain that we’re full and can stop eating. When low, we feel hungry and crave food. It does this by stimulating receptors in our hypothalamus, the part of our brains which regulates the hormone system in our bodies. When leptin binds to receptors in this part of our brains, it stimulates the release of appetite-suppressing chemicals. People with leptin disorders eat uncontrollably.

     

    Your leptin LEVEL is high when you are full, low when you are hungry

    Now here’s the strange part.  Leptin is produced mostly by our adipose tissue – aka our fat.  The level of circulating leptin is directly proportional to the total amount of fat in the body.  That means the more fat you have, the greater the amount of leptin you have. It may seem counter-intuitive, but it makes sense in the end when we consider how yo-yo dieting tends to be. It takes some time for your body to adjust to large changes in body fat levels when it comes to leptin.

    The total AMOUNT of leptin you have is related to your weight

    So when you lose a lot of weight quick, via liposuction or serious calorie restriction, your leptin levels plummet. Subsequently, you get hungrier, your thyroid decreases output and your metabolic rate drops. Your body then increases catabolic hormone activity and appetite, making you tend to slip off your regime and gain all that weight right back. That’s why crash diets are often ineffective – your leptin won’t let you eat less, and even if you do, you’re lethargic and your metabolic rate slows way down.

    Of course, just because it makes things difficult for dieting, leptin levels are far more sensitive to starvation than overeating. So when you cut caloires and start ot burn fat, the leptin levels in your body plummet, but when you eat too much they don’t skyrocket – although they do increase. Leptin levels increase with increased insulin levels, like right after eat, and when our body is storing energy. Keeping this in mind, in general, can help you eat healthier and loser weight in the long run.

    The Science of Leptin

    Obviously, since leptin is so key to hunger and feeling full, scientists have been looking into it as a possible target for anti-obesity or weight loss. As it turns out, leptin controls a lot more than just our feelings of fullness.

    Turning on leptin in the brains of mice causes them to exercise more, according to research from Harvard Medical School. It’s interwoven into how our bodies control our metabolism, activity levels, and energy budgeting – like immediately increasing appetite when fasting. While levels drop quickly, eating can bring them back up, too. It has been shown to reduce lipids in muscle and other tissues which lead to insulin resistance (the first step towards type 2 diabetes). It even controls what foods we find appealing when we’re just looking at them. Basically, it seems like the perfect way to lose weight – just give people more leptin,  right?  Well, there is another factor at work.

    Leptin Resistance

    But when researchers gave people leptin in human clinical trials, people didn’t lose weight. The trouble is, your body constantly tries to adjust basal leptin levels. If there’s a lot of it all the time, like in obese and overweight people, the brain loses sensitivity. Mice can become leptin resistant after as few as 3 days of overfeeding – so it happens quickly in response to consistent high blood glucose levels.

    When obese, your leptin LEVELS spike radically because you have higher leptin AMOUNTS in your body (causing leptin resistance in the brain)

    When it does this, it takes more and more leptin before our bodies feel full. When we get fatter, our bodies produce more leptin, and we become resistant to it. So obese people actually have unusually high leptin levels, but are not responsive to it. Even when healthy people eat a much lower calorie diet for a little while,  levels decrease, and they feel hungrier and less energetic, even if they haven’t lost weight yet. To lose weight and keep it off, you have to give your body time to adjust to the new, lowered leptin level, so it sets that as “normal” and you feel full when you’re supposed to.

    Yes, he is.

    The bad news is that not just excess weight can lead to leptin resistance. A new study published in the American Journal of Physiology found that high fructose diets can induce leptin resistance. These sugars actually impair the leptin’s ability to cross the blood-brain barrier and reach the hypothalamus. So even when the leptin levels are high, not enough is reaching the brain to tell the body to stop eating.

    How do you use this information to lose weight or keep healthy?

    First things first: quit the crash diets. You aren’t going to do your body any favors by losing weight too quickly. If you are trying to lose weight, though, there’s one thing you can do to help your body out: cheat. Seriously.

    When you cut calories dramatically, your body acts like its starving and your leptin levels plummet. You’ll be hungry and generally have lower energy levels and want to eat more. So, once a week or so, cheat. Really cheat. Have a nice, high-calorie meal.

    Your body then senses the rush of fuel and boosts leptin levels, increasing your metablism and priming your body for fat loss. Cheating helps ease your body down to lower daily leptin levels without making it feel too starved. That way, as you lose the weight, your body adjusts and realizes that the reduced leptin levels are normal not starving. And you get to enjoy something delicious – come on, it’s a win-win!

    A beautiful sockeye salmon

    Secondly, avoid too much sugar intake. High calorie loads aside, the sugars make your brain less sensitive to leptin, which causes you to eat more and pack on the pounds. Conversely, some foods have been shown to increase leptin activity and sensitivity. The biggest connection scientists have found is between Omega-3 Fatty Acids and leptin. That’s right – the ever remarkable fish just keep getting better and better.  Researchers found that a group of people who ate a high proportion of fish every day had lower leptin levels despite eating the same calorie loads and having the same body fat as their fish free cousins – suggesting that a fish-rich diet increased their bodies’ sensitivity to leptin.

    There’s good news, too, for those that are already overweight and leptin resistant: it’s only temporary. Research has shown that reducing fat content in leptin-resistant, obese mice allowed them to regain leptin sensitivity. So even if you’re overweight and likely leptin resistant, you can improve on that state. Unlike type 2 diabetes and insulin resistance, which is very hard to reverse, leptin resistance is fairly correctable with a normal, healthy diet and exercise.

    And lastly, there’s something really simple that everyone can do to keep their leptin levels high and keep cravings under control: sleep well. When you go to sleep, your leptin levels naturally rise – after all, you want to be sleeping, not snacking, so your body knows to cut down on your hunger while you’re resting. But if you cut your sleeping short, your body tries to adjust by making you hungry again. Research has found that shorter sleep periods (6 hours or less instead of 8) lower overall daily leptin levels, cause an increase in appetite, and even make people crave carbs and other fattening foods. So its important for your body to rest well to maintain its natural hormonal balance, allowing you to look and feel your best.

    In summary:

    • Stop crash diets
    • Eat ONE large meal per week to spark leptin-based weight loss
    • Avoid processed sugar
    • Eat Omega-3 (in fish/flaxseed/walnuts)
    • Sleep well

    Like any other system in our bodies, the our hormonal appetite controls are sensitive to our daily habits and routines. The better a routine you have – sleeping well, eating right, and exercising, the more balanced your system will be and the better you will feel.

    Stay tuned for more deep dives into the physiology of nutrition with the next installment of Understanding Our Bodies!

    References:

    1. Williams, K., Scott, M., & Elmquist, J. (2009). From observation to experimentation: leptin action in the mediobasal hypothalamus American Journal of Clinical Nutrition, 89 (3), 985-990 DOI: 10.3945/ajcn.2008.26788D
    2. Havel, P. (2007). Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance Proceedings of the Nutrition Society, 59 (03) DOI: 10.1017/S0029665100000410
    3. Huo, L., Gamber, K., Greeley, S., Silva, J., Huntoon, N., Leng, X., & Bjørbæk, C. (2009). Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons Cell Metabolism, 9 (6), 537-547 DOI: 10.1016/j.cmet.2009.05.003
    4. Pratley RE, Nicolson M, Bogardus C, & Ravussin E (1997). Plasma leptin responses to fasting in Pima Indians. The American journal of physiology, 273 (3 Pt 1) PMID: 9316457
    5. Chin-Chance C, Polonsky KS, & Schoeller DA (2000). Twenty-four-hour leptin levels respond to cumulative short-term energy imbalance and predict subsequent intake. The Journal of clinical endocrinology and metabolism, 85 (8), 2685-91 PMID: 10946866
    6. Enriori, P., Evans, A., Sinnayah, P., Jobst, E., Tonelli-Lemos, L., Billes, S., Glavas, M., Grayson, B., Perello, M., & Nillni, E. (2007). Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons Cell Metabolism, 5 (3), 181-194 DOI: 10.1016/j.cmet.2007.02.004
    7. Zelissen, P., Stenlof, K., Lean, M., Fogteloo, J., Keulen, E., Wilding, J., Finer, N., Rossner, S., Lawrence, E., Fletcher, C., McCamish, M., & , . (2005). Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial Diabetes, Obesity and Metabolism, 7 (6), 755-761 DOI: 10.1111/j.1463-1326.2005.00468.x
    8. Wang, J., Obici, S., Morgan, K., Barzilai, N., Feng, Z., & Rossetti, L. (2001). Overfeeding Rapidly Induces Leptin and Insulin Resistance Diabetes, 50 (12), 2786-2791 DOI: 10.2337/diabetes.50.12.2786
    9. Keim NL, Stern JS, & Havel PJ (1998). Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. The American journal of clinical nutrition, 68 (4), 794-801 PMID: 9771856
    10. Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, & Scarpace PJ (2008). Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. American journal of physiology. Regulatory, integrative and comparative physiology, 295 (5) PMID: 18703413
    11. Peyron-Caso E, Taverna M, Guerre-Millo M, Véronèse A, Pacher N, Slama G, & Rizkalla SW (2002). Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. The Journal of nutrition, 132 (8), 2235-40 PMID: 12163668
    12. Winnicki M, Somers VK, Accurso V, Phillips BG, Puato M, Palatini P, & Pauletto P (2002). Fish-rich diet, leptin, and body mass. Circulation, 106 (3), 289-91 PMID: 12119240
    13. Enriori, P., Evans, A., Sinnayah, P., Jobst, E., Tonelli-Lemos, L., Billes, S., Glavas, M., Grayson, B., Perello, M., & Nillni, E. (2007). Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons Cell Metabolism, 5 (3), 181-194 DOI: 10.1016/j.cmet.2007.02.004
    14. Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller DA, & Penev PD (2009). Sleep curtailment is accompanied by increased intake of calories from snacks. The American journal of clinical nutrition, 89 (1), 126-33 PMID: 19056602
    15. Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index PLoS Medicine, 1 (3) DOI: 10.1371/journal.pmed.0010062