Sanae Ferreira
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What’s in a name? That which we call “sweet” by any other name may not be the same.

Sweeteners_Sanae Ferreira

Sweeteners_Sanae Ferreira

In the case of Shakespeare, a rose is a rose is a rose – all smell sweet. But, in the case of sweeteners, the story is not quite so simple.

 

Here are a couple of scenarios that may look familiar to you:

 

– You’ve sat down at your favorite breakfast place, and your server has asked if you would like some coffee or tea while you consider the menu. A carafe appears, your cup is full, and you instinctively reach for the narrow box containing a rainbow of packets. You reach for one, but are curious about the rest – what are they really?

– You’re at the store, trying to buy something to drink, and there are words you don’t recognize on the label next to “sugar-free.”

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Olivia Rivera
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Why women are at greater risk for major depression and cardiometabolic comorbidities

Major depressive disorder (MDD) is the leading cause of disability in the U.S. for persons ages 15-43, affecting 16.2 million adults. Furthermore, depression is comorbid with other prevalent, chronic conditions including cardiovascular disease (CVD) and obesity/metabolic syndrome (MetS). MDD alone is almost twice as prevalent in women compared to men, and women have a 62% increase in risk for comorbidities with MDD. Comorbidity of MDD with CVD is predicted to be a primary cause of disability worldwide by 2020, posing significant public health implications for women.

A Common Mechanism of Disease

MDD, CVD, and obesity/MetS have been independently linked to changes in the body’s response to stress. Stressors, including inflammation, overnutrition, and undernutrition, stimulate a route of communication that relays information from the body to the brain. The brain responds to these challenges by sending signals resulting in behavioral and physiological changes. This communication circuit is known as the hypothalamic-pituitary-adrenal (HPA) axis and a primary signal is cortisol, the most common glucocorticoid. MDD symptoms have been linked with elevated cortisol, as a result of disease (Cushing’s syndrome) or when given as glucocorticoids. MDD affects regions of the brain that are stimulated by cortisol, sex steroid hormones, and inflammatory signals. Consequently, these regions then communicate to regulate metabolism and cardiac function. Therefore, the relationship between MDD, CVD, and obesity/MetS is not surprising from a physiological perspective.

The Role of the Prenatal Environment

Studies in both humans and rats have indicated that suboptimal conditions during pregnancy, resulting in excess maternal cortisol production and inflammation, increase the risk for MDD, CVD, and obesity/MetS in offspring. Stressful prenatal conditions include a low protein diet, high salt diet, high fat diet, and malnutrition. Prenatal stressors can impact programming of the HPA axis, resulting in long-term changes into adulthood. These changes result in hyperactivity and extension of the glucocorticoid response to stress in adults.

Why are women at greater risk?

Interestingly, the same maternal stressors produce different responses in male and female offspring. This can be partly attributed to differences in the size of regions of the brain that respond to and regulate the HPA axis. These regions are implicated in regulating mood, cardiac function, and metabolism, and are abnormal in patients with MDD. Physical differences in the anatomy of the brain are a result of differences in exposure to gonadal steroid hormones, such as testosterone and estrogen, during critical periods of development. These are characterized as permanent changes. However, short-term changes can also occur with fluctuations in gonadal steroid hormones, or in response to sex-dependent differences in circulating levels of these hormones (https://doi.org/10.1113/jphysiol.2004.078212).

These findings have widespread implications in that they suggest: 1) a shared developmental origin of multiple diseases and 2) sex dependent differences in the changes underlying diseases development. Further investigation into sex differences will be critical to the treatment of MDD comorbid with CVD and obesity/MetS in both women and men.

 

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Sarah Dimitratos
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The shopper’s Dilemma: To Shun Or Embrace The Center Aisles?

Which consumer are you?

–The astute academic or health professional: You have a degree (one or more) in nutrition, you have PubMed bookmarked on your internet browser, and you spend your days dispelling nutrition myths and/or researching the next nutrition breakthrough.

–The health foodie. You scour wholesome recipes online, you already know the nutrition trends for 2019, you make detailed grocery lists like it’s your job, you’re a #mealprepsunday veteran, and always know where to find the best deals for natural/organic/raw/fresh eats.

–The bachelor/broke student: Is it cheap? Edible? Delicious? Easy to prepare? If yes, it goes in the cart.

–The athlete with phenomenal sport skills, and (developing) culinary know-how: You know that the foods you eat influence your athletic performance. You are game for eating better, under one condition: you need quick/easy foods that pack a nutritional punch.

–The busy parent: There are lunches to make, picky eaters to feed, and you can’t remember the last time you enjoyed a calm, healthy mealtime at home. Grocery shopping is typically a stressful battle between your healthy intentions, and the little ones’ demands for sugary cereals and flashy marketing.

Photo Credit: Lifehacker

Whether you identify with one or multiple distinct categories listed here, each one is unified by a few common underlying themes:

We all eat.

We crave amazing flavors.

There are never enough hours in the day.

We really do have good intentions; We want to eat well.

Assuming we don’t grow/hunt/gather our own food, we cross paths with one another for a common purpose: Food Shopping! On that note, we’ve been exposed to the same rules of thumb for healthy grocery shopping:

-Shop the perimeter!

-Steer clear of the middle aisles!

The way I see it, there are two types of people in this world: Those who love the center aisles (but could use a little strategy for picking the best options), and those who openly shun those aisles (but are secretly curious to explore the forbidden foods within).

As a health professional, it’s my duty to pass along this tried-and-true advice. But as a real-life RD on a budget, I hear you: Those middle aisles are mighty tempting, so what’s a guy/girl to do?

Take a deep breath, direct that grocery cart towards those center aisles, keep your eye on the prize and walk with intention because you have a fool-proof plan. Healthy shoppers, unite! Today, you’ll conquer those middle aisles like the savvy consumer you are.

Photo Credit: The Sports Nutrition Coach

Your strategy: Divide and conquer by food group like so:

Whole grains, legumes, and pseudograins: Instant oatmeal, frozen brown rice or quinoa (that’s a pseudograin), ready-to-serve plain cooked rice, Grape Nuts (for impressive iron and fiber content), popcorn, Vaccuum packed pre-cooked lentils (that’s a legume), whole grain bread (can you find bread with 0-1g sugar per serving? Can you find fiber above 2g per serving?)

Fruits and vegetables: Frozen is your friend! These items are picked at peak ripeness and flash-frozen immediately afterwards. Canned items are fine as well (in light syrup or water). Can you get all colors of the rainbow?

Protein: Canned beans, canned tuna, canned chicken, canned salmon, frozen chicken strips (no breading), hummus

Dairy: single serve plain Greek yogurt (Ok, you’ll find this in the perishables, but this is too versatile not to include), string cheese

Fats: Olives, frozen Cool Whip, prepared guacamole

Snacks: Dark chocolate (Pro-tip: Pick one with single-digit grams sugar per serving), nuts (try pistachios, almonds, or walnuts), dried fruit, jerky, whole grain chips, hummus

Drinks: Chocolate milk

Spreads/flavorings: Sriracha, olive oil, balsamic vinegar, mustard, pesto

Photo credit: Smile Sandwich

 Once you return home from this über successful grocery trip, you’ll want to assemble some stellar meals using your new bounty. Try this one-day sample plan:

Breakfast: Yogurt cup topped with frozen fruit, Grape Nuts, nut butter (purchase single serve packets in a pinch!) Feeling extra hungry? Prepare a side of instant oatmeal

Lunch: Tuna sandwich (canned tuna mixed w/ mustard, Ezekiel bread). Side of green salad (found in deli section)

Snack: Handful of nuts, handful chips, and hummus

Post Workout: Classic PB&J, or chocolate milk

Dinner: Defrost that frozen rice, quinoa, or lentils, frozen veggies of choice, top w/ beans (and/or thawed ready-to-eat chicken), salsa, pre-made guacamole, and Sriracha

Dessert: 2-3 squares of dark chocolate, alongside frozen blueberries w/ a dollop of cream

Not everyone has a nutrition coach by their side, but you, ASN reader, have an edge. Use this guide to confidently navigate the previously forbidden center aisles. Print it, internalize it, share it. No nonsense, no gimmicks. Blasphemy? Hardly. Creative and backed in science? Absolutely.

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Chris Radlicz
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The Value of Nutrition Obesity Research Centers: As Told by Dr. David Allison

Doctor David B. Allison is the current dean, distinguished professor, and provost professor at the Indiana University School of Public Health-Bloomington. Prior to Indiana University, Allison was a distinguished professor, Quetelet Endowed Professor, and director of the NIH-funded Nutrition Obesity Research Center (NORC) at the University of Alabama at Birmingham (UAB). Allison was appointed director of the NORC in 2003 and served until 2017. Allison has published more than 500 scientific papers with research interests including obesity and nutrition, quantitative genetics, clinical trials, statistical and research methodology, and research rigor and integrity.

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NORCs are “intended to integrate, coordinate, and foster interdisciplinary basic, clinical, translational, and public health research by a group of established investigators actively conducting programs of important, high-quality research that is related to research specific to NIDDK’s mission.”

There are currently twelve university-based NORCs across the United States from New York to Washington State. These centers are funded by P30 Center Core Grants from the NIDDK to bring together investigators who are conducting research in nutrition and obesity and improve the quality of research by promoting multidisciplinary work and sharing access to specialized technical resources and expertise. These centers allow for cost-effective collaboration between groups of investigators at the same institution. The NORC at UAB currently has 159 investigators from 58 different academic units – a manifestation of the center’s multidisciplinary approach.

Allison’s 14-year appointment as director of UAB’s NORC makes him an ideal individual to speak with about the successes of the initiative since its inception in 1999. Allison was gracious enough to answer several questions about his tenure as director and about NORCs more broadly.

What role do you see NORCs playing on university campuses?

NORCs are enormously helpful, and it is valuable to consider them in a historical context. The first NORC – before they were even called NORCs – was the New York Obesity Research Center at Columbia University and, at the time, Rockefeller University. It was the first and for many years only federally funded obesity research center in the United States. The NIDDK subsequently decided to call all the clinical nutrition research units and obesity nutrition research centers “NORCs,” and there are now twelve under this designation.

The New York center is where I started my career as an obesity researcher during my second postdoc. It was a lot of fun there. The NY Obesity Research Center was the mecca of obesity research. If you were an obesity researcher, and if you wanted to get trained, you knew where the mecca was. If you wanted to make a pilgrimage, you could see what the great leaders of the field were doing. You could go there and meet esteemed individuals such as Ted VanItallie, Xavier Pi-Sunyer, and Steven Heymsfield.

You sort of knew where the leadership was – where the intelligentsia and cognoscenti were. There were certainly other places in the world that were powerhouses in obesity, but in the United States, the NY Obesity Research Center served as a galvanizing force. It also served as a great training ground at the time – and NORCs still do. It is one of the things that makes NORCs special: they are multidisciplinary, and they are focused on a topic.

What you sometimes see in the field of obesity, which is probably true in other fields as well, is that there are a lot of instances of people making mistakes that I refer to as “errors in interdisciplinarity.” This is an error which one makes because one is completely unaware of something that would be basic and fundamental to someone in another discipline – but you as a member of a different discipline aren’t aware of it.

A simple example would be if you are a social scientist and you know that physical activity matters for obesity, and you make an assessment that some program will have an important effect, but you don’t know anything about body mass or energetics. You then project the amount of weight change that could occur because of the physical activity intervention without understanding the physics, the mechanics, or the energetics. This is an error of interdisciplinarity.  We see these things regularly.

When I was “growing up” in the NY Obesity Research Center, these kinds of things would become the fodder of your education as a young person. So if you piped up and raised your hand in a seminar and said, “What about this?” it may reveal that you didn’t understand a basic concept in statistics, psychology, physiology, or anatomy. Then the more senior people around, who were experts in those things, would say to you, “Come on over here, kid, let’s explain to you that’s not how that works.” You got it drilled into your head, an emphasis of interdisciplinarity – the idea of real expertise – and avoiding these simplistic mistakes that you still see so often now in people who are focused on obesity research. That is one very valuable part of it: bringing together an interdisciplinary cadre of experts on the topic who then educate young people to be an expert in a topic, and not just get caught up in their own discipline.

The second thing that is extremely valuable is the idea of the NORC as provocateurs of people’s interests. The total amount of money in the NORCs per se is not much – around $750k/year in direct costs – not much bigger than one or two R01s. What is important is not the total cash value, but the way the value is delivered through a leader on campus, who then uses the funds as a lever, at the right points to provoke activity, and provoke interests.

Years ago, early in the NORC’s history at UAB, it became clear to me that using more invertebrate models for obesity was important, that genomics was upon us, and that we should have people working with Drosophila and C. elegans. I was able to use different pieces of the NORC to provoke that. For example, I would bring in speakers through our seminar series who worked on those topics. We had funding for pilot grants that could be used on that research. There were extra discretionary funds from institutional matching, so I could use those funds to recruit some younger people to work on these topics. All those things came together so that people were writing and getting R01s to do research involving those organisms.

There are other things that are important for the NORC in terms of sense of identity.  People are excited to be at an NORC because they feel that they are at one of “the” places. The dollar amount of the NORC isn’t that great, but the prestige value is high. It serves to create an identity to get people excited – to pull them together to work together on things. Those are some of the big values of the NORCs today.

You were director of the NORC at the University of Alabama at Birmingham for nearly 15 years. How have you seen the effect of NORCs change over that time?

I think we have seen a couple of changes. In general, science has changed, and the NORC science has changed with it. Science has become more molecular, more genetic, and the NORCs keep up with the trends of general science. Other things I have seen in NORCs is this idea of leveraging the amount of money. Not only is the amount of money provided by the direct costs of the NORC not large, especially compared to diabetes centers, cancer centers, and other NIH centers that receive much more than NORCs, but it’s been flatlined for over 20 years. If you compared the NORC funds in real dollars to the dollars from 20 years ago, the current funds are much smaller.

NORCs have become these engines – at their best – where creative leaders use the P30 grants as the nucleating site around which to build other stuff. You go to your institution and get a match in funds, and then you get some T32 grants. You say, “Isn’t this great we have an NORC, so we can do great training. Please give us a postdoctoral and predoctoral T32 in obesity, and then why don’t you give us an R5 to do a national short course in obesity?” … You keep adding those things on. We at UAB were very strong on that. Many other institutions are as well, and that is one way you have seen the NORCs change. They have become these multi-infrastructure grant organizations.

When speaking with other NORC directors and center administrators, what are some of the advances and successes that have stood out to you?

I think probably more than anything, the successes and advances that I hear the NORC directors take the greatest pride in is the young people who they help get started, and that is especially true for those NORCs that go on to get T32s, which many have. How I got my own start was on a T32 while in New York. That is also how I learned to write T32s, by being thrown into it by my old boss at the NORC. He said, “Here’s my old folder. I’m going on a trip out of the country. I will be back after this thing is due. Good luck,” and I said “…okay,” and so I learned how to write a T32 grant.

I think when people are successful in getting those T32 grants, as well as in getting young people involved, however they do it, bringing new people into the field, and helping those new people achieve, it is a great success. You can look at many of us and say that we are products of the NORC systems themselves. Myself, Doctors Dympna Gallagher, Tim Nagy, Barbara Gower, Michael Goran, and many others, are all the products of these centers, brought in as postdocs at the beginning of a center. Many who are NORC directors now got their start there.

How do NORCs help cultivate the future generation of nutrition and obesity researchers?

To reiterate, the interdisciplinarity: training people so they are not just a public health person that says, “Yeah I get it, people, they eat too much and exercise too little, what else do I need to know about obesity. Now I just need to talk about the policies that will make people eat less and exercise more.” Well, maybe it would be good to know a little more than that. NORCs bring up people with a more robust knowledge of this. The NORCs also draw people into the field, give them a sense of identity and belonging and an enthusiasm for being in the field.

You have been critical of the rigor at which obesity and nutrition research is performed. Do you think that NORCs have been able to increase the quality of research in the field?

I think that NORCs do increase the quality of research in the field, and they lead by example. I am critical of the rigor and quality of the research everywhere, including in my own research. That is important for us to do as scientists – to be critical of the rigor and the quality of research – and to make it better. I think there are particular concerns raised in the field of obesity, and some of those concerns in my mind came out in the mid-90s when obesity began to be seen as a public health crisis.

Instead of obesity research being driven to a greater extent by people who were fully involved in it for a long time, and involved with others in getting this interdisciplinary background, it became more that anybody felt that they can jump in. Any economist, any public health official, jumped in with zealous passion, which much of the time wasn’t matched with rigorous background knowledge. This has led to some of the more questionable research we have seen. It’s not everything, but just one factor. NORCs are helping by providing training for people, by putting out good research, and by leading by example.

What are some fond memories from your time at UABs NORC

Well, pulling together on things in general. Part of what makes a great center great is people working together as a center. In fact, one of the things that attracted me to come down to UAB was in fact its centeredness. I had other offers before heading to UAB, and some were at institutions that were more attractive in some ways, but what I liked about UAB and the NORC was the feeling that this was a group of people that worked together, and only a slight exaggeration, but it was a sense of a family. I really liked that. To me, a lot of my fondest memories were pulling together with Tim Nagy, Barbara Gower, José Fernández, Tim Garvey, the late Roland Weinsier, Stephen Barnes, Steve Austad, Kevin Fontaine, Julie Locher, Gary Hunter, and I am sure I’ve missed many important people, but the ability to pull together through tough challenges, working hard, overcoming obstacles – doing things together which none of us could have done alone.

 

This is part two of a two-part interview with Dr. David Allison.

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Chris Radlicz
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The Need for Increased Rigor in Obesity and Nutrition Research: A Q&A with Dr. David Allison

Doctor David B. Allison is the current dean, distinguished professor, and provost professor at the Indiana University School of Public Health-Bloomington. Prior to Indiana University, Allison was a distinguished professor, Quetelet Endowed Professor, and director of the NIH-funded Nutrition Obesity Research Center (NORC) at the University of Alabama at Birmingham (UAB). Allison was appointed director of the NORC in 2003 and served until 2017. Allison has published more than 500 scientific papers with research interests including obesity and nutrition, quantitative genetics, clinical trials, statistical and research methodology, and research rigor and integrity.

In addition to his primary appointments, Allison is a co-director for two NIH-funded “Short Courses” on obesity research held in Birmingham, Ala., during the summer. Dr. Allison’s “Short Course on Mathematical Sciences in Obesity Research” is going on its fifth consecutive year, while the “Short Course on Strengthening Causal Inference in Behavioral Obesity Research” is coming up on its fourth consecutive year. These interdisciplinary courses convene a cadre of expert faculty members who teach on various aspects of obesity research, covering economics, epidemiology, statistics, genetics, and much more. These courses are oriented toward investigators who want to increase the rigor in their approach to obesity research, and they bridge various disciplines in which obesity research is performed. Allison took the time to answer a few questions regarding the ability to better approach obesity and nutrition research.

You have noted that the rigor of obesity research has been lacking. Has there been a shift in recent years?

I don’t have unequivocal data as to whether there has been a shift in recent years in obesity research or research overall. I have a hypothesis though, which is when you look within any one journal, research is getting ever more rigorous, whereas when you look across all journals, it may be getting less rigorous because of the influx of new journals.

If you take a journal like the American Journal of Clinical Nutrition, they keep getting more rigorous. That is in part because the editor-in-chief, Dr. Dennis Bier, has a very strong commitment to that, and he has built an associate editorial board who shares the commitment. Meanwhile, other journals keep springing up that are not as rigorous. So for the overall quality of the literature, I am not sure if it is going up or down, since you have these competing factors.

One of the things my colleagues and I are writing a paper on now is the childhood obesity intervention literature, which seems to be particularly susceptible to distortion. We hypothesize that this has to do with feelings of zealousness – the idea that childhood obesity is such a problem and it must be addressed. To come out after an expensive and effortful intervention and say, “Guess what, I did an intervention and it just didn’t work, so let’s move on.” People just don’t want to say that. They want to instead say, “But it must work, we can’t tell people not to do this, especially if we don’t have something better, so let’s twist and bend and ‘find a pony in there’.” We see a lot of “spin” in these things, and that is an area where things seem to have become worse.

What are your suggestions to researchers in the field to increase conscientiousness in limiting and being transparent about shortcomings in the quality of the research produced?

I think there are different aspects to it. Some aspects to it, and perhaps related to what I was saying about the childhood obesity literature, is that people, often again with good intentions, are bending the truth. I think that we need to continually remind ourselves that we are scientists and reflect on why we all got into science in the first place. To be a scientist means to pursue truth through the scientific method. We have to affirm that speaking the unvarnished truth is an uncompromisable imperative. Commitment to one’s identity as a scientist is something to be held dear.

Then, I think there are some things that are more skill-level. Many errors I see – and partially because this is my expertise, so I see what I understand and know about – are statistical errors. One of the challenges is that the norm for many years was, and still is, that many scientists should be able to conduct their own statistical analyses. Physicians are generally not trained with this mentality, because they get very little training in statistics. They accept that they will need to go to a statistician – most at least. Whereas if you are trained in a field like nutrition, psychology, physiology, or biology, you get a PhD in that, and you get one or two statistics courses as you earn your PhD, often taught by that same department. The person who teaches that course tends to not be a professional statistician, but rather a physiologist, biologist, or nutritionist who knows a little statistics. What you are getting is kind of an intelligent amateur who is running the statistics for professional research.

If you think about that – it’s the equivalent of me saying that I need to get a kidney surgery and I say, “Well, I have an anatomy book. I know approximately where my kidneys are. I have a bottle of hand sanitizer. I can get some rubber gloves and a pocket knife, and I can do it myself.” Well, no. Just because you have an anatomy book and you know where the kidneys are and you understand the idea of surgery doesn’t mean you are a professional surgeon, and we wouldn’t have you do it. Why take a different view about statistics? Part of what we are currently exploring, since statisticians are in limited supply, is how we can get more professional statisticians to be involved with more papers, and how can we create a culture and an economic situation that would permit that.

Is there an overreliance on observational research in nutrition/obesity studies? If so, why is this the case?

I think there is sometimes a reliance on observational studies for situations in which they are not what I would call “probative.” For example, you can think, “Well, maybe Pokémon GO is going to reduce obesity levels.” No-one has ever looked at it, so sure, go ahead and do an observational study. Do people who start using Pokémon GO lose weight or gain less weight? And that is fine, there is nothing wrong with that. You might even want to replicate it once or twice. But if you say, “Well, now we’ve done that, so let’s do 20 more of those,” then you need to wonder why you need the next 20. Maybe you need one more to confirm it, but not 20 more. What you see is people not shifting out of the observational and into the experimental when it is called for. For example, breakfast consumption, fruit and vegetable consumption, things like that – when people continue to grind on the observational literature long after it is really useful.

You have noted that you see many errors in obesity and nutrition related meta-analyses. How would you caution investigators in interpreting these papers?

I would say, interpret with a grain of salt, particularly if there isn’t a professional statistician on there. The issue is that there is software out there, where it is seemingly easy. You plug in a few numbers, and it spits out a meta-analysis for you. The problem is, you need to know what numbers to plug in. That is where the problem, the challenge, and the mistakes often occur. Particularly, these mistakes seem to occur around variances. I would caution anybody who is going to do a meta-analysis who thinks, “Oh, meta-analyses are easy. I can just get a grad student to grab some papers, write the numbers down, and plug them in some public software.” I would caution people not to do that, but to have a professional statistician involved.

You have published articles criticizing the statistics and assumptions of various academic papers, resulting in their retractions. Can you theorize why these papers are being published in the first place? What are some mistakes that you see most often?

Why they get published in part is because we don’t really have a good system for vetting papers. Many people seem to think that peer review is that system, but I don’t think it was ever realistic to expect that peer review can be the true gatekeeper of papers and can eliminate all mistakes – or even most mistakes. I think peer review just checks if a paper belongs, and then you receive advice. But the peer reviewers don’t have the time and the ability to go through everything the author and investigator did to see if it is correct. That must fall on the investigators themselves. I think many investigators let a lot slip through – some intentional and some unintentional. I think we need to work on both of those things.

What would you recommend to young researchers in the field of obesity and nutrition who would like to improve their ability to identify poor methods and conclusions?

I would say to take our short courses. Read very widely, including interdisciplinary work. Read some work on the physiology of obesity, the genetics of obesity, engineering approaches, computational approaches, nutritional, psychology, medical, and economic approaches, so that you have a broad base to compare things to. I would say to talk broadly and question everything. Question yourself. Question your own ideas. Those are all important things to do.

 

This is part two of a two-part interview with Dr. David Allison.

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Sarah Dimitratos
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Inflammation: What Is It, and how can my diet and behavior affect it?

Suppose you’ve been told to eat an anti-inflammatory diet, or maybe you’re a practitioner whose clients want to know whether this is right for them. Before hopping on this buzzy bandwagon, ask yourself ‘For what purpose?’

Without missing a beat, you say ‘Well, to reduce my inflammation!’

While technically a noble intention, let’s first acknowledge that this term is used loosely in everyday conversation, but it’s more misunderstood than one might initially believe. Let’s talk about this elephant in the room, dive in, and answer a few key questions: What’s inflammation in the first place? What factors (dietary and otherwise) contribute to, or mitigate it? And finally, how might we modify our diets and our behavior to reduce it?

 

creative-diagnostics.com

What is inflammation?

In broad terms, inflammation is the body’s immune system’s response to a stimulus.1This can be in response to common injuries such as burning your finger, or falling off of a bicycle, after which you feel the affected area become red, warm, and puffy- this is a localized response to injury, characterized by ‘increased blood flow, capillary dilation, leucocyte infiltration, and production of chemical mediators.’2In short, an inflammatory response means the innate (non-specific) immune system is ‘fighting against something that may turn out to be harmful.’

It turns out that while inflammation is often cast in a negative light, it’s actually essential in small amounts for immune-surveillance and host defense.2 In true ‘Goldilocks’ form, too little and too much inflammation both pose problems; in fact, most chronic diseases are thought to be rooted in low-grade inflammation that persists over time. This inflammation may go unnoticed by the host (you!) until overt pathologies arise, which include, but are not limited to, diabetes, cardiovascular disease, nonalcoholic fatty liver disease, obesity, autoimmune disorders, inflammatory bowel disease, and even clinical depression. This concept is called ‘The inflammation theory of disease,’ in which inflammation is the common underlying factor among the leading causes of death.3

How do we measure inflammation?

Although measuring low-grade chronic inflammation (read: A chronic, low-grade immune response) carries a number of limitations, studies frequently measure cellular biomarkers such as activated monocytes, cytokines, chemokines, various adhesion molecules, adiponectin, non-specific markers such as C-reactive protein, fibrinogen, and serum amyloid alpha. Key inflammatory pathways include sympathetic activity, oxidative stress, nuclear factor kappaB (NF-kB) activation, and proinflammatory cytokine production.4 Now you might wonder, ‘What does this mean for me? What modifiable factors can activate my key inflammatory pathways?’ If we are to address this question appropriately, let us turn our attention to both dietary and behavioral moderators.

cbsnews.com

What makes up an anti-inflammatory diet?

Prolonged low-grade inflammation is associated with excessive oxidative stress and altered glucose and lipid metabolism in our fat (adipose) cells, muscle, and liver.4 Therefore, research suggests that certain dietary components can modulate these key inflammatory pathways and clinical pathologies. Dr. Barry Sears explains in a review paper that “anti-inflammatory nutrition is the understanding of how individual nutrients affect the same molecular targets affected by pharmacological drugs.” 5

Compelling research from large-scale, longitudinal observational studies including the Women’s Health Initiative Observational Study6 and Multi-Ethnic Study of Atherosclerosis (MESA) study7suggest that a diet with appropriate calories that is low in refined carbohydrates, high in soluble fiber, high in mono-unsaturated fatty acids, a higher omega-3 to omega-6 ratio, and high in polyphenols, all have anti-inflammatory effects on the body. A Mediterranean diet pattern that incorporates olive oil, fish, modest lean meat consumption, and abundant fruits and vegetables, legumes, and whole grains, shows more anti-inflammatory effects when compared to a typical American dietary pattern. Other observational and interventional studies have also suggested that dietary patterns incorporating green and black tea, walnuts, ground flaxseed, and garlic are also associated with reduced inflammation.

drmarkhyman.com

 

Can my stress levels influence inflammation, too?

To conclude our discussion with anti-inflammatory dietary strategies would be a half-told story. In fact, “Communication between the systemic immune system and the central nervous system (CNS) is a critical but often overlooked component of the inflammatory response to tissue injury, disease or infection.”3

Behavioral studies have shown that prolonged psychological stress can activate the same pro-inflammatory pathways we’ve been discussing all along. While chronic psychological stress can promote over-expression of pro-inflammatory mediators, it can also promote overeating unhealthful foods in the absence of hunger. 8 Repetitively stress-eating calorie-dense, nutrient-poor foods not only further exacerbates psychological distress and creates a vicious cycle of stress-eating, but over time promotes adiposity, which we’ve described is itself a pro-inflammatory state.

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Integrative strategies and considerations

This ‘cross-talk’ between the brain and body suggests that strictly dietary or strictly behavioral interventions are not enough to reduce inflammation on their own. Instead, we must consider integrative diet and lifestyle preventions/interventions simultaneously. Going forward, we’ll need better biomarkers and more research looking at individual responses to diet (personalized nutrition!), and better understanding of how food components and behavioral factors modulate genetic targets involved in the inflammatory response.

 

References:

  1. What is an inflammation? National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072482/. Published January 7, 2015. Accessed March 16, 2018.
  2. Hunter P. Stress, Food, and Inflammation: Psychoneuroimmunology and Nutrition at the Cutting Edge. EMBO Reports. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492709/. Published November 2012. Accessed March 16, 2018.
  3. Hunter, Philip. The Inflammatory Theory of Disease. EMBO Reports, Nature Publishing Group, Nov. 2012, ncbi.nlm.nih.gov/pmc/articles/PMC3492709/.
  4. Galland, Leo. “Diet and Inflammation.” Sage, 7 Dec. 2010, journals.sagepub.com/doi/abs/10.1177/0884533610385703?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed.
  5. Sears, Barry, and Camillo Ricordi. “Anti-Inflammatory Nutrition as a Pharmacological Approach to Treat Obesity.” Journal of Obesity, Hindawi Publishing Corporation, 2011, ncbi.nlm.nih.gov/pmc/articles/PMC2952901/.
  6. Thomson, C A, et al. “Association between Dietary Energy Density and Obesity-Associated Cancer: Results from the Women’s Health Initiative.” Journal of the Academy of Nutrition and Dietetics., U.S. National Library of Medicine, ncbi.nlm.nih.gov/pubmed/28826845.
  7. “Associations of Dietary Long-Chain n-3 Polyunsaturated Fatty Acids and Fish With Biomarkers of Inflammation and Endothelial Activation (from the Multi-Ethnic Study of Atherosclerosis [MESA]).” The American Journal of Cardiology, Excerpta Medica, 4 Mar. 2009, www.sciencedirect.com/science/article/pii/S0002914909001088?via=ihub.
  8. Tryon, M., Carter, C., DeCant, R. and Laugero, K. (2013). Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits. Physiology & Behavior, 120, pp.233-242.
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Sarah Purcell
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How can we implement better health behaviors in cancer survivors?

Lifestyle interventions targeted at obtaining/maintaining a healthy body weight and/or incorporating physical activity and healthy eating habits have great potential in improving outcomes in cancer survivors. Cancer diagnosis is a “teachable moment” wherein many patients are highly motivated to make changes (1). Furthermore, a balanced diet and moderate exercise can improve prognosis, quality of life, physical function, and survival across the cancer continuum. As such, groups such as the Amercian Cancer Society, National Comprehensive Cancer Network and the American College of Sports Medicine have released lifestyle guidelines for cancer survivors.

However, implementing changes in individuals and healthcare systems is challenging, to say the least. This is a recent topic covered by Karen Basen-Engquist and a number of colleagues as part of a special Issue of Obesity (Transdisciplinary Research on Energetics and Cancer)(2). Their article provides a 6-point agenda for translating research into clinical and community action, as follows:

  1. Increase the availability of different types of activities for weight management, nutrition counseling, and physical activity. One size will never fit all when it comes to improving health. Individual goals/preference, resources, and logistics all come into play, and cancer-specific programs may be needed.
  2. Improve screening and referral to lifestyle interventions. A system for evaluating and triaging patients for health programs should be developed. Importantly, an individual’s physical status, health needs, and goals should be considered.
  3. Improve the health care provider’s ability to screen, assess, and refer survivors for lifestyle programs. Oncology providers have a powerful role in helping cancer survivors; however, they often do not feel confident in screening, giving advice, or administering recommendations for lifestyle-related constructs. Implementation of processes such as the 5As (Ask, Advise, Assess, Assist, Arrange), which has been successful in tobacco cessation (3) and obesity management (4) might prove beneficial.
  4. Expand the support of oncology-specific professional training and certification. Professional organizations of dietitians, exercise professionals, psychiatrists, and physical therapists have additional certification programs for oncology or are working on developing one for its members. However, professionals with specific expertise in oncology are still greatly needed to address the unique needs of this population.
  5. Expand dissemination and implementation research. Many research programs do not address how a program could be implemented in a real-world setting (external validity). Dissemination of research findings with consideration of the sustainability and generalizability of programs is essential for broader impact.
  6. Advocate for health care policies that support lifestyle services for cancer survivors. Coverage for health programs is highly variable and often has barriers such as large co-payments, no coverage in grandfathered plans, and cost sharing. A potential solution could be incentivizing nutrition and exercise services, although more research is needed to determine the effectiveness of such actions.

As the authors eloquently articulate, the time has come to enable research into action for optimal healthcare in all cancer survivors.

References:

  1. Demark-Wahnefried W, Aziz NM, Rowland JH, Pinto BM. Riding the crest of the teachable moment: promoting long-term health after the diagnosis of cancer. J Clin Oncol 2005;23:5814–30.
  2. Basen-Engquist K, Alfano CM, Maitin-Shepard M, Thomas CA, Schmitz KH, Pinto BM, et al. Agenda for Translating Physical Activity, Nutrition,and Weight Management Interventions for Cancer Survivors into Clinical and Community Practice. Obesity 2017; 25, S9-S22.
  3. Siu AL, Force USPST. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2015;163:622-634.
  4. Rueda-Clausen CF, Benterud E, Bond T, Olszowka R, Vallis MT, Sharma AM. Effect of implementing the 5As of Obesity Management framework on provider-patient interactions in primary care. Clin Obes 2013; 4, 39-44.

 

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Mary Latimer
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I eat what you eat: Maternal Nutrition and Epigenetics

Potential mothers, new mothers and mothers of multiples often worry about how their nutrition will affect their children. With the high rates of childhood obesity, some mothers worry more than ever about what they are putting in their bodies. Although this could be a discussion that includes pesticides on food, chemicals in cleaners and even air pollution, let’s just focus on nutrition.

 

It has been shown that a strong predictor of a child’s future BMI is the mother’s pre-pregnancy BMI (Schou-Anderson et al, 2012). This prediction comes from two sources, environment (how parents eat directly influences how children eat) and genetics (especially epigenetics). Epigenetics is how our cells control gene expression without changing the core DNA sequence and can include both DNA methylation and histone modification. It is consistently reported that maternal diet can directly alter DNA binding sites (Aagaard-Tillery et al, 2008) and DNA methylation (Dudley et al, 2011) in the offspring of mothers fed high fat diets. High fat diets contain energy dense foods consisting of >45% of total calories from fat, essentially mirroring the typical Western diet, which is full of highly palatable, highly processed energy dense foods. While this is certainly not a comprehensive list of publications on this topic, it is safe to say that maternal diet can influence an offspring’s risk of developing obesity through epigenetics (a nice review here). Hence the idea that whatever you eat, your baby also experiences.

 

While this may not be a novel concept, it is more important than ever to educate mothers (and fathers!) about the influence their diet could have on their future children’s body composition and their overall risk for obesity-associated diseases. While this information may initially leave parents anxiously asking questions like “Is there anything I can do?!”; “Is the damage already done?”; or “What could I have done differently?”, our goal is to provide information that is both reassuring and accurate knowing that with the right nutritional decisions, your child will be just fine!

 

Multiple studies have shown interventions in eating patterns and exercise work for reducing obesity and risk for associated diseases (reviewed here, here, here, here, here etc.).

 

The trick? Implementing these changes in your families diet and exercise routines to change the trajectory that epigenetics may have imposed when your little one was no larger than a grain of rice.

 

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Mary Latimer
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Breastmilk from a Bottle and Obesity Risk

As a new parent you can go no longer than 24 hours without hearing the phrase “Breast is Best.” I know this to be true because I became a parent in June of this year. In the hospital we were offered consults with lactation and had no less than six posters in our room touting the benefits of breastfeeding. As a PhD student I was intrigued by the literature behind these recommendations and eagerly spent multiple late night nursing sessions on my iPad reading the latest research. What I found were some studies finding associations with reduced risk of obesity, and others failing to find this same association (literature). Overall, it was concluded in the previous review that breastfeeding was associated with a reduced risk of obesity.

While this was great news, I could not help but question; was this association because of breastmilk or mode of delivery? Bottle feeding is typically associated with formula feeding but a growing number of women have begun pumping their breastmilk after returning to work or in cases of pre-term birth and latch issues.

Could bottle feeding breastmilk still ameliorate the risk of obesity later in life?

I was not the first person to raise this question which has been addressed here, here, here, and here. Overall the consensus seems to be that early bottle feeding, of breastmilk or formula, is associated with an increased risk for excess weight gain and poor self regulation. Exclusively feeding expressed milk is also associated with early cessation of breast-milk feeding.

So this leads to the inevitable question; what is a mother to do?

While the literature is still unclear if bottled breastmilk can fight obesity risk, it is clear the breastmilk has multiple other benefits according to the American Academy of Pediatrics and should be offered when possible. So to those mothers who pump a little, a lot, or all the time, I say pump on ladies!

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asnutrition

Moving Beyond BMI – An Evaluation of an Alternative Adiposity Index and Mortality Risk

By Caitlin Dow, Student Blogger

Body Mass Index. BMI, for short. Those three words tend to conjure up some intense feelings in scientists and the general public, alike. In 1832, a Belgian statistician named Adolphe Quetelet created his namesake index, the Quetelet Index, to describe the normal variation seen in weight relative to height across populations. That index got its new name “Body Mass Index” in 1972 from Ancel Keys (1) and was  by the World Health Organization as a clinical tool to be used easily and effectively to determine levels of obesity.

 

As Cyndi Thomson, PhD, RD, a professor in the College of Public Health at the University of Arizona points out, “BMI was meant for population evaluation and we keep applying it to individuals.” BMI is useful when we study populations. It predicts risk for development of a number of chronic diseases (2). However, applying BMI to individuals, which is likely not what Quetelet had in mind when he created it, creates a number of issues. While BMI correlates well with fat mass on a population (but not necessarily on an individual level), it certainly does not consider distribution of fat. This is important because plenty of data indicate that abdominal fat predisposes people to a number of health risks more so than fat distributed evenly throughout the body (2). Furthermore, associations between BMI and various outcomes like risk for disease or mortality are assumed to be linear. That is, as BMI increases, risk for disease also increases. However, some cross-sectional, epidemiological studies have shown a “U-shaped” relation between BMI and mortality (3,4), meaning that people with very low or very high BMIs are at elevated risk of dying within a given period of time than those in the middle (generally overweight) range. The increased mortality risk with normal BMIs later in life is actually probably due to smoking or weight loss due to disease (like cancer), but this hasn’t stopped the media from concluding that “being overweight is good for you!” Due to these shortcomings of BMI, it is high time to consider/develop some type of index that (a) has a linear relation with mortality for ease of interpretation; (b) considers fat mass and/or distribution; and (c) can be used easily in both research and clinical settings.

 

To address this need, new adiposity indices are being studied that may provide more clinical and scientific utility than BMI. A body shape index (ABSI) considers waist circumference (a surrogate measure of abdominal adiposity), adjusted for height and weight and was first developed by Krakauer, et al (5). Cyndi Thomson and colleagues recently published a paper in Obesity evaluating the relation between ABSI and mortality risk in a very large cohort study (6). The analysis included over 77,500 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. Anthropometrics were measured at baseline and the women were followed for an average of 13.5 years. Similar to previous findings, a U-shaped association between BMI and mortality was demonstrated. However, ABSI was strongly and positively associated with mortality, such that those in the highest quintile of ABSI had a 37% increased risk of death compared with those in the lowest quintile.
 

I discussed the implications of these findings with Dr. Thomson over the phone. The results from this study that indicate that ABSI is associated with mortality in postmenopausal women support similar findings from a smaller cohort from the British Health and Lifestyle Survey (7). However, while ABSI may be a more robust index describing the effect of adiposity on mortality risk, it’s not ready for clinical implementation. First, because it is so new, there are no standard reference values or categorical values that correspond with normal or excessive adiposity. As Dr. Thomson says, “ABSI may provide some additional information that informs on risk, but I think we still have the issue of people not measuring waist circumference [clinically].” Because waist circumference requires more than standing on a scale, it has been difficult to implement. Clinicians have to be trained on how to properly measure waist circumference, and while it is inexpensive and not overly complicated to learn, accuracy and inter-individual measurement techniques are an issue. Despite these current setbacks, she remains optimistic: “The measurements haven’t gotten there, but they will.”

 

Another important aspect of using ABSI (or any index of body composition) will be validating it across a range of races and ethnicities. Thomson notes that in a preliminary analysis that has yet to be published, the ABSI and mortality risk does indeed differ between races and ethnicities. Because of that, “one clinician may use one [adiposity index] while another may use something else, depending on their patient population.”

 

Although still in the preliminary stages of research, ABSI may pan out as a useful measure of adiposity that could replace or complement BMI. It will need to be rigorously tested across age groups, race/ethnicities, genders and in its associations with a variety of chronic diseases. Stay tuned as this very young area of research unfolds!

 

References
1. Keys A,  Fidanza F, Karvonen M, Kimura N, Taylor H. Indices of relative weight and obesity. Journal of Chronic Diseases 1972; 25 (6–7): 329–43.
3.Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 2013; 309:71-82.
4.Winter JE, Macinnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysis. Am J Clin Nutr 2014;99:875-890.
5.Krakauer NY, Krakauer JC. A new body shape index predicts mortality hazard independently of body mass index. PloS One 2012;7:e39504
6.Thomson CA, Garcia DO, Wertheim BC, Hingle MD, Bea JW, Zaslavsky O, Caire-Juvera G, Rohan T, Vitolins MZ, Thompson PA, Lewis CE. Body shape, adiposity index, and mortality in postmenopausal women: Findings from the Women’s Health Initiative. Obesity; 2016; 1061-9.
7.Krakauer NY, Krakauer JC. Dynamic association of mortality hazard with body shape. PloS One 2014;9:e8879.
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