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?

 

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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.

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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.

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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.

Student Blogger for Global Nutrition Council at ASN’s Scientific Sessions and Annual Meeting at EB 2016

By: Sheela Sinharoy, MPH

A symposium called Biology of Linear Growth on Tuesday examined linear growth from the molecular to the population level, bringing perspectives from biology, physical anthropology, nutrition, and epidemiology

Are you familiar with the process of endochondral ossification? Julian Lui, MD PhD explained that this is the process that results in linear growth. It takes place in the growth plates, at the end of long bones such as the femur, and is subject to systemic regulation by endocrine, nutritional, and inflammatory cytokine factors as well as local regulation by paracrine factors and other cellular mechanisms. Malnourished children have lower levels of hormones like insulin-like growth factor 1 (IGF-1) and estrogen, as well as increased levels of glucocorticoids, leading to decreased linear growth. Dr. Liu explained that this allows the body to conserve resources and that, in situations of food insecurity, “Growth is something of a luxury that can be postponed until better times.”

Rather than growing continuously, children grow in saltations, meaning that – as many a parent has observed – a child may grow substantially overnight and then not at all for a number of days afterwards. Michelle Lampl, MD PhD stated that as children age, these saltations become less and less frequent, with older children growing much less often than infants. The amount and frequency of these growth saltations can be affected by environmental factors, which can interact with cellular effects. Maternal smoking, for example, has a well-documented inhibitory effect on growth, as does maternal alcohol consumption and stress.

Since linear growth happens most rapidly in early life, the first 1,000 days from conception to two years of age are considered a critical period. Parul Christian, DrPH presented results from a meta-analysis analyzing various maternal and child nutrition interventions targeting this 1,000-day window. Starting during pregnancy, balanced protein-energy, iron-folic acid, and multiple micronutrient supplementation were all found to increase birth weight. However, maternal supplementation during pregnancy was not associated with any long-term linear growth in children under five years old. For infants and young children, nutrition promotion and food supplementation showed promise as interventions with positive impacts on child height.

In the final talk of the symposium, Aryeh Stein, PhD addressed the question of linear catch-up growth: for those children whose growth has been suppressed by malnutrition, is it possible to catch up on missed growth, even after the first 1,000 days? A number of studies have provided different nutrients and foods to children ages two and older. Dr. Stein presented results from studies of protein, zinc, iron, iodine, calcium, multiple micronutrients, and food. Protein and some of the micronutrients may have promise, but several of the calcium studies reported negative effects, while food had no association with growth.

The symposium made it clear that nutrition has an important role to play in stimulating or inhibiting linear growth. However, a great deal remains to be learned about these complex biological processes and the most effective interventions to promote children’s optimal growth.

By: Hassan S Dashti, PhD

The most popular New Years resolution by far is weight loss. People kick-start their new year on new ‘detox’ or fad diets with hopes to lose some weight or, less commonly, to adopt a healthy lifestyle, only to quit a few months later. Traffic to websites like caloriecounter.com and weightwaterchers.com hits an all time high in January! (1) People often envision January 1 of every year as an empowering and motivating moment that enables them to consider making these daring lifestyle changes. People might be less inclined to make these commitments on arbitrary dates like March 1 or October 19. With emerging evidence suggesting seasonal changes in the environment and human physiology, driven primarily by seasonal changes in sunlight and temperature, is it possible that certain start dates or seasons are more conducive to successful weight loss?

Seasonal variations have been observed for numerous communicable and non-communicable diseases (2) and both biological and behavioral traits. One of the earliest observations of seasonal variation in a disease was that of rickets, a disease resulting from vitamin D deficiency (3). Clinical observations indicated that rickets was common in spring, but rare in fall. The subsequent finding of seasonal variation in plasma 25(OH)D levels suggested that summer sunlight exposure was indeed an important determinant of vitamin D status. For more complex traits, like obesity, the seasonal etiology, if present, is likely to be multifactorial!

Successful weight loss is largely determined by the ability to reduce overall caloric intake, which depends on food availability and internal hunger cues. Living at a time where food is essentially abundant year-round in the Western world, people are typically not dealing with food shortages. For most processed foods, seasonal price variability is also absent, particularly in metropolitan areas, so people’s intakes are likely to be homogenous year-round (4,5). However, seasonal price variability of nutrient dense fruits and vegetables may limit a person’s likelihood to adhere to diets higher in fruits and vegetables. For example, strawberry prices tend to decrease through the first four months of the year and rise again from September to December. Fresh apples, on the other hand, have a fairly weak seasonal price pattern as a result of new apple varieties with later harvest dates and sophisticated storage technology. But it seems that despite the constant supply of most foods at steady prices, seasonal variation in dietary intake may exist. In the Framingham Heart Study, for example, self-reported total energy intake was 86 kcal/day higher during the fall than in the spring (6). Also, percentage of calories from carbohydrate, fat and saturated fat showed slight seasonal variation, with a peak in the spring for carbohydrate and in the fall for total fat and saturated fat intake. Of course these differences may be due to seasonal differences in self-reporting and recall, but if it’s true, is weight loss in the spring more successful than the fall?

Another important aspect of weight loss to consider is seasonal variability in energy expenditure.

The investigation from the Framingham Heart Study (6) also observed seasonal variation in physical activity, including common activities such as gardening, carpentry, lawn mowing, golf and running for men, and gardening, swimming, health club exercise, dancing and bicycling for women. Not surprisingly, people residing in the Northeast are less inclined to engage in outdoor physical activity. This sedentary lifestyle in the winter may partly explain the reason why people tend to be the heavier in the winter! (7)

Newer studies are investigating more complex physiologic changes that might interfere with energy balance. Recent observations in humans suggest that cold exposure may induce the conversion of white adipose tissue to more metabolically active brown-like adipose tissue (8). This ‘beiging’ effect of cold exposure could potentially have clinical implications for diabetes and obesity. Other studies have observed seasonal variability in metabolism and epigenetics as well (9,10). Whether these physiologic differences can override energy imbalance resulting from seasonal lifestyle differences is currently unknown.

To test whether there are seasonal differences in weight loss success we’d ideally test this in a randomized and controlled weight loss trial whereby people are prescribed hypocaloric diets and assigned random start dates. This can also be investigated analytically in previously conducted weight loss cohorts. Various methodologies are available for the assessment of seasonality and those range from simple comparisons across seasons, to simple models such as fitting monthly counts to a sine curve, or more complex statistical models (2).

Despite the little evidence we have so far relating seasonality and energy balance, healthcare providers, including nutritionists, should account for seasonality in their practice, and tailor their dietary (food and fluids) and physical activity recommendations accordingly – it’d be senseless to recommend berries when they are unavailable at stores or outdoor exercise when it’s uncomfortably warm! But perhaps reaching that point of enthusiasm for weight loss is the most important factor predicting weight loss success, so if January 1 is that date when motivation hits in, then so be it!

References:

2.Christiansen CF, Pedersen L, Sørensen HT, Rothman KJ. Methods to assess seasonal effects in epidemiological studies of infectious diseases–exemplified by application to the occurrence of meningococcal disease. Clin Microbiol Infect. 2012 Oct;18(10):963–9.
3.Stamp TC, Round JM. Seasonal changes in human plasma levels of 25-hydroxyvitamin D. Nature. 1974 Feb 22;247(5442):563–5.
4.Evolving U.S. Fruit Markets and Seasonal Grower Price Patterns, by Kristy Plattner, Agnes Perez, and Suzanne Thornsbury, USDA, Economic Research Service, September 2014
5.Bernstein S, Zambell K, Amar MJ, Arango C, Kelley RC, Miszewski SG, et al. Dietary Intake Patterns Are Consistent Across Seasons in a Cohort of Healthy Adults in a Metropolitan Population. J Acad Nutr Diet. 2016 Jan;116(1):38–45.
6.Ma Y, Olendzki BC, Li W, Hafner AR, Chiriboga D, Hebert JR, et al. Seasonal variation in food intake, physical activity, and body weight in a predominantly overweight population. Eur J Clin Nutr. 2006 Apr;60(4):519–28.
7.Visscher TLS, Seidell JC. Time trends (1993-1997) and seasonal variation in body mass index and waist circumference in the Netherlands. Int J Obes Relat Metab Disord. 2004 Oct;28(10):1309–16.
8.Iyengar P, Scherer PE. Obesity: Slim without the gym – the magic of chilling out. Nat Rev Endocrinol. 2016 Feb 26.
9.van Ooijen AMJ, van Marken Lichtenbelt WD, van Steenhoven AA, Westerterp KR. Seasonal changes in metabolic and temperature responses to cold air in humans. Physiol Behav. 2004 Sep 15;82(2-3):545–53.
10.Aslibekyan S, Dashti HS, Tanaka T, Sha J, Ferrucci L, Zhi D, et al. PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population. Chronobiol Int. 2014 Jul 30;:1–7.

By Chris Radlicz

According to NHANES (National Health and Nutrition Examination Survey) 2005-2010 the average American consumes about 20 teaspoons of sugar per day, with sugar consumption being the highest in teens and men (1). Interestingly, 33% of calories from added sugars come from beverages, and the majority of those beverages are sweetened with high fructose corn syrup (HFCS) (1).

But what is the novelty of HFCS? Aren’t the grams of sugar on the package all that matters? Although calorically equivalent, not all sugars are metabolized the same way.

Previous papers have established epidemiological links between fructose consumption, obesity, and metabolic disease. To take this further, recent literature has indicated that fructose, particularly in high concentrations, as present in high fructose corn syrup and sucrose, are proving to be toxic. HFCS is composed of about 60% fructose and 40% glucose (2). Prior to the processing of sugars, it was nearly impossible to find such high concentrations of sugar in the diet, but it now seems to be commonplace.

Dr. Kimber Stanhope out of University of California Davis published a recent review paper that touched on the metabolic dysregulation that occurs with high consumption of fructose.

Dr. Stanhope’s group has previously shown that subjects consuming fructose-sweetened beverages for 10 weeks, in addition to their normal diet, had increased de novo lipogenesis, dyslipidemia, circulating uric acid levels, visceral adiposity, reduced fatty acid oxidation, and insulin resistance. In contrast, subjects who consumed glucose-sweetened beverages, had comparable weight gain to the fructose group, but did not exhibit the aforementioned metabolic changes (3). These adverse effects seen in the fructose group all increase the likelihood of chronic diseases such as obesity, fatty liver, type-2 diabetes, and cardiovascular disease.

When consuming glucose, the liver is initially bypassed and the glucose reaches systemic circulation to be used by tissues such as the brain and muscles. If excess glucose is consumed in the diet, it will first be stored as glycogen, and secondarily as fat. Fructose on the other hand, takes a different path. When fructose is consumed, it is exclusively metabolized in the liver, where a particular enzyme, fructokinase, will allow for the uptake of fructose (3). Fructose metabolism as a whole lacks many of the cellular controls that are present in the glucose metabolism, which allows for unrestrained lipid synthesis (2).

Significant metabolic issues arise when a high concentration of fructose is consumed, such as in HFCS. An overload of fructose in the liver will lead to de novo lipogenesis and subsequent lipid droplet accumulation in the liver. With these high levels of fructose, the increase in lipid accumulation consequently decreases the breakdown of fat in the liver (3).

This intra-hepatic lipid will promote the production and secretion of very low-density lipoprotein 1 (VLDL1) leading to an increase in post-prandial triglycerides. A vicious cycle occurs effecting insulin resistance as well. The lipid in the liver will increase insulin resistance resulting in increases in circulating diacylglycerol. Additionally, the insulin resistance will lead to further lipid deposit in the liver with sugar having a greater propensity to turn to fat (3). A downstream effect of increased apoCIII and apoB will lead to muscle lipid accumulation, and end in whole body insulin resistance. All of this metabolic dysregulation results from the direct route fructose initially takes to the liver.

Although there is this well-defined and unique pathway for fructose metabolism, many industry-funded studies, haven’t shown the negative metabolic outcomes of consuming HFCS or sucrose (3). More research is certainly needed, but it is best to remember that added sugar in such high concentrations, no matter the culprit monosaccharide, is not favorable for overall health.

It is interesting to note a possible evolutionary perspective, which proposes the advantage of enhanced fructose to fat conversion. At the end of a growing season, ripened fruit will tend to have high levels of fructose. Therefore the fruit consumed at the end of the season may allow for increased fat storage, which would have been beneficial because of the low food availability in the ensuing months (2).

1.U.S. adults, 2005– 2010. NCHS data brief, no 122. Hyattsville, MD: National Center for Health Statistics. 2013.

2.Lyssiotis CA, Cantley LC. F stands for fructose and fat. Nature. 2013; 508:181-182.

3.Stanhope KL. Sugar consumption, metabolic disease and obesity: The state of the controversy. Crit Rev Clin Lab Sci. 2015;1-16.

By Hassan S Dashti, PhD

When we describe our habitual diets, we often find ourselves talking about its nutritional composition (i.e. what) and quantity (i.e. how much), however novel research suggests that timing of intake might be yet another important component of diet we want to pay attention to. This was the main focus of discussion at the ASN Scientific Sessions at EB 2015 symposium titled, “Is ‘When’ We Eat as Important as ‘What’ We Eat? – Chronobiological Aspects of Food Intake” (read more here: https://www.nutrition.org/asn-blog/2015/04/timing-is-everything/). Biologically, this makes sense as an endogenous clock, commonly termed the circadian clock, regulates a constellation of biologic processes, including metabolism (1). If up to 30 percent of genes in the intestines, liver, and kidney fluctuate throughout the day, yielding varying temporal functional profiles, doesn’t it make sense that there ought to be a time when dietary intake is optimal? Well, if the effect of a calorie on health is dependent on timing, what we all would like to know next is at what time should we be eating?

What currently determines our timing of intake is our culture and lifestyle for the most part. For instance, kids’ lunchtime is predetermined by school cafeterias, adults’ dinnertime is predetermined by rush-hour traffic, but even breakfast also seems to determine when we’ll have our next meal, lunch (2). History also played a role in determining meal times. In certain parts of the world, lunchtime was set for noon to enable workers to cope with long working hours in factories during the Industrial revolution. Perhaps it’s time to have science determine our meal hours.

Preliminary evidence suggests that earlier meal times tend to be healthier and “better aligned” with our biological clock. In one study, it was found that calories consumed after 8:00pm significantly predicted higher BMI (3). Meanwhile results from a 20-week weight loss intervention among overweight and obese individuals suggested that late eaters (lunch after 3:00pm) were less successful at weight loss compared to early eaters (lunch before 3:00pm), independent of 24-hour energy intake (4). Another trial assessing overweight and obese women further identified that high-calorie breakfasts, as opposed to high calorie dinners, were more beneficial for various cardiometabolic traits (5). Consistent with the findings from these trials is a cross-sectional analysis of a diverse cohort in the Los Angeles area that suggested that participants who consumed over a third of their calories by noon were less likely to be overweight and obese (6).

While these findings generally suggest that earlier hours of intake are generally healthier, they are not without their many limitations. One limitation worth noting is the high interrelatedness between timing of intake and other aspects of diet and life that also impact overall health and particularly sleep timing and duration, frequency of intake, and hours of fasting. Therefore, future studies should account for these strongly related dimensions when elucidating the timing of intake that best aligns with our internal clock.

1.Garaulet M, Gómez-Abellán P. Timing of food intake and obesity: a novel association. Physiol Behav. 2014 Jul;134:44–50.
2.Kant AK, Graubard BI. Within-person comparison of eating behaviors, time of eating, and dietary intake on days with and without breakfast: NHANES 2005-2010. Am J Clin Nutr. 2015 Sep;102(3):661–70.
3.Baron KG, Reid KJ, Kern AS, Zee PC. Role of sleep timing in caloric intake and BMI. Obesity (Silver Spring). 2011 Jul;19(7):1374–81.
4.Garaulet M, Gómez-Abellán P, Alburquerque-BÉjar JJ, Lee Y-C, Ordovás JM, Scheer FAJL. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Apr;37(4):604–11.
5.Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Dec;21(12):2504–12.
6.Wang JB, Patterson RE, Ang A, Emond JA, Shetty N, Arab L. Timing of energy intake during the day is associated with the risk of obesity in adults. J Hum Nutr Diet. 2014 Apr;27 Suppl 2:255–62.

By Caitlin Dow, PhD

Breakfast is often considered the “most important meal of the day,” and if you are looking to lose weight, you mustn’t skip breakfast… or so the story goes. This idea is widely believed in popular culture as well as by many nutrition scientists and government bodies and is repeated so often that many in the field consider it health dogma. Indeed, the Dietary Guidelines for Americans even recommend breakfast consumption as an important tool for weight loss. But what does the science say?

Observational studies indicate that breakfast consumption is linked to lower weight. Data from the National Weight Control Registry demonstrated that 78% of the nearly 3,000 subjects included in the analysis (adults who had lost at least 13 kg and kept the weight off for a year or more) reported eating breakfast everyday and only 4% reported never eating breakfast [1]. Further, a recent meta-analysis of observational studies that have evaluated the relation between weight and breakfast consumption found that skipping breakfast was associated with a 55% increased odds of having overweight or obesity [2]. These findings are likely the reason many tout breakfast consumption as an important weight loss modality, despite these studies not actually testing that outcome.

Observational studies can only describe associations, but are not appropriate to determine causation. Thus, randomized controlled trials (RCTs) have sought to test whether breakfast consumption directly impacts weight. In one of the first RCTs to evaluate the role of breakfast in weight loss, Schlundt et al. [3]studied women with obesity who were self-reported breakfast eaters or skippers.Within each group, women were randomized to eat or skip breakfast in addition to following a 1200 kcal/day diet for 12 weeks. All groups lost at least 6 kg, but interestingly, those who were randomized to switch their breakfast condition (e.g. ate breakfast at baseline, then started skipping) lost more weight than those who maintained their breakfast habit. These results suggest that changing an eating behavior in addition to following a reduced calorie diet may accelerate weight loss. However, the results from a study by Dhurandhar et al. did not corroborate those findings. Adults with overweight and obesity were randomized to one of three conditions in which all groups received a USDA pamphlet on healthy eating practices: the control group received no other information, one group received additional instructions to consume breakfast, and the third group was instructed to not eat breakfast [4]. After 16 weeks, there was no observed effect of treatment assignment on weight loss.Contrary to the results from the Schlundt study, baseline breakfast eating habit was not related to weight change, though this study didn’t evaluate breakfast consumption in conjunction with a reduced calorie diet.Finally, in a recently published 4-week study, adults with overweight and obesity were randomized to three different breakfast conditions: water (control), frosted flakes, or oatmeal [5].Interestingly, skipping breakfast resulted in an average weight loss of 1.2 kg, while those randomized to either breakfast condition demonstrated no significant weight change.However, total cholesterol also increased in the control group, suggesting that skipping breakfast may result in slight weight loss, but have detrimental effects on cardiometabolic health.

Thus, the results from the few RCTs completed in adults with overweight and obesity, to date, do not support the notion that breakfast consumption should be part of a weight loss regimen. Importantly, though, the results are also not compelling to suggest that eating breakfast hinders weight loss. This field is still young and many questions remain unanswered. I look forward to more RCTs evaluating breakfast consumption (and potentially, breakfast quality) on various facets of weight and metabolic health.

References

1.Wyatt, H.R., et al., Long-term weight loss and breakfast in subjects in the National Weight Control Registry. Obes Res, 2002. 10(2): p. 78-82.

2.Brown, A.W., M.M. Bohan Brown, and D.B. Allison, Belief beyond the evidence: using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence. Am J Clin Nutr, 2013. 98(5): p. 1298-308.

3.Schlundt, D.G., et al., The role of breakfast in the treatment of obesity: a randomized clinical trial. Am J Clin Nutr, 1992. 55(3): p. 645-51.

4.Dhurandhar, E.J., et al., The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial. Am J Clin Nutr, 2014. 100(2): p. 507-13.

5.Geliebter, A., et al., Skipping breakfast leads to weight loss but also elevated cholesterol compared with consuming daily breakfasts of oat porridge or frosted cornflakes in overweight individuals: a randomised controlled trial. J Nutr Sci, 2014. 3: p. e56.

By Teresa L. Johnson, MSPH, RD

“A calorie is a calorie, but the body’s physiological response to that calorie might be different depending on the circadian phase the body is exposed to,” said Frank Sheer, PhD, an assistant professor of medicine at Harvard Medical School. Sheer spoke during ASN’s scientific symposium titled “Is ‘When’ We Eat As Important As ‘What’ We Eat?—Chronobiological aspects of food intake.” He opened his discussion by asking why we should care about circadian biology, and then pointed to its possible influence on metabolic processes, meal timing, and disease risk. He explained that an internal “circadian clock”—present in nearly all the body’s cells—regulates the body’s rhythms based on feedback from the brain. We can uncouple those rhythms and choose to be awake, but at a cost, possibly increasing our risk of some chronic diseases, like type 2 diabetes.

Jonathan Johnston, PhD, an associate professor at University of Surrey, “flipped the question on its head,” so to speak, and asked what effect meal timing might have on the body’s internal clock. Johnston explained that circadian rhythms are endogenous and self-sustaining even without external cues, like light and darkness. “Clocks are everywhere,” Johnston said, “and they function like an orchestra.” All the “musicians”—the various clocks—have to be synchronized to function properly, he said. Johnston’s data, gleaned from gene expression studies in human adipose tissue, suggest that modifying meal times might help synchronize the body’s clocks, a possible treatment for the circadian dyssynchrony commonly observed with shift work, jet lag, blindness, and sleep disorders.

“Humans are the only species that disobeys their biological clocks,” said Fred Turek, PhD, a professor at Northwestern University, and the downstream effects might be enormous. We have become “night creatures,” he said, and he and his colleagues are wondering how that affects human health. Turek pointed out that at least 10 to 30 percent of gene expression in the human body is under circadian control including genes in tissues like the brain, liver, and muscle—key players in metabolism—and likely influences disease risk, gut permeability, and the gut microbiota. He suggested that science is at a tipping point with regard to circadian medicine and health, adding that the field of circadian biology is growing and spans many different disciplines, including immunology, oncology, cardiology, and nutrition. “I think it’s the next frontier in medicine,” Turek said.

Jose Ordovás, PhD, a professor at Tufts, explained that circadian rhythms extend beyond 24-hour cycles to monthly and seasonal patterns, a phenomenon now ingrained in human physiology. Ordovás suggested that humans’ ancestral genes were more like the genes of the laboratory animals he studies, which respond to regular cycles of light and dark. Migration away from humans’ equatorial origins likely has altered human circadian biology and, in fact, circadian clocks now vary depending on geographical location. Ordovás speculated on the potential application of circadian biology in personalized or precision medicine as a means to identify those at risk for nutritional disease, and added, “Know your genome and act accordingly.”

By Ann Liu, PhD

Researchers are using carrots to produce a new tracer that will help scientists study vision and brain function. The results of this study were presented in the “Carotenoid and Retinoid Interactive Group: Bioavailability and Metabolism of Carotenoids and Vitamin A” on March 29 by Joshua Smith and John Erdman, PhD, from the University of Illinois at Urbana-Champaign.

Lutein is a carotenoid which accumulates in the retina of the eye and may protect the eyes from damage, especially age-related macular degeneration. It also accumulates in certain areas of the brain and may be beneficial for cognitive performance. However, little is known about how lutein accumulates in tissues such as the brain or how these tissues metabolize it. This led researchers to embark on a mission to develop lutein labeled with a non-radioactive, stable tracer (carbon-13) as a tool to study the metabolism of lutein in tissues.

Enter the colorful carrots. Carrots are a good source of lutein, but the amount of lutein can vary depending on the variety of carrot. Researchers tested seven different carrot cultivars that ranged in color from red to yellow to purple to see which one produced the most lutein. Then they had to culture the carrot cells in flasks and optimize the growing conditions to increase lutein production.

Once they figured out the optimal growing conditions, the carrot cells were fed carbon-13 labeled glucose. The lutein then had to be extracted using reverse-phase high performance liquid chromatography, and incorporation of the carbon-13 tracer was assessed using mass spectrometry. Approximately 58% of the lutein extracted from the carrot cells was uniformly labeled with carbon-13.

So what’s next for this new tracer lutein? The researchers plan to use it to study tissue accumulation of lutein in animal models before embarking on any studies in humans. They will also be going back to the lab bench to see if there are any more changes they can make to further improve their lutein yield.

This research was funded by a grant from Abbott Nutrition through the Center for Nutrition, Learning, and Memory at the University of Illinois.

By Kevin Klatt

A few weeks ago, I had the pleasure of reading Allyson West and Marie Caudill’s Research and Practice Innovations paper in the Journal of the Academy of Nutrition and Dietetics, entitled “Applied Choline-Omics: Lessons from Human Metabolic Studies for the Integration of Genomics Research into Nutrition Practice” (1). The publication elegantly describes how integrating metabolomic, transcriptomic and genetic/epigenetic approaches into traditional controlled feeding studies can help refine the Dietary Reference Intakes, and elucidate the mechanisms by which choline and folate contribute to overall health.

Referencing the Nutrition Research Priorities established by the American Society for Nutrition (ASN) in 2013 (2), we can clearly see that the approaches described by West and Caudill fall in line with ASN’s thinking on how to advance the field of nutritional sciences. The Nutrition Research Priorities report specifically highlights furthering our understanding of nutrition and health by pursuing –omics research to understand individual responses to nutrients. For me, it was encouraging to see these kinds of advanced techniques and their clinical applications representing the field of research in a major clinical nutrition journal.

Fast-forwarding to this past week, I found myself staring at headlines inflaming the conversation around the newest low-carbohydrate/low-fat research, published in the reputable Annals of Internal Medicine (3). The publication is a randomized trial that ultimately concludes “the low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet”. Being in such a high profile journal and funded by the NIH, one would expect this publication to add some significant perspective to our understanding of energy balance and disease progression, two areas also highlighted in the 2013 Nutrition Research Priorities report. Unfortunately, upon reading the paper, one is quickly underwhelmed by the lackluster weight loss over 12 months, the poor accuracy of the dietary recall data, the lack of any information about diet quality, the use of imprecise measurement techniques, and the authors’ failure to discuss alternative conclusion, beyond just the low-carbohydrate component of the diet. I have specifically detailed the limitations of this trial elsewhere.

As I finished reading the study, West and Caudill’s ‘Choline-omics’ paper came to mind, and I couldn’t help but feel frustrated: why are we still funding these overly reductionist paradigms of low-carb vs low-fat, when much more integrative and informative approaches are being taken? To quote the 2013 Nutrition Research Priorities report on the topic of energy balance:
“A systems approach is preferable because the standard experimental approach of varying one factor at a time has accomplished little to address the population-wide problem of energy imbalance.”
Yet here we are, still trying (and failing) to vary only one factor, and publishing it in a premier journal for physicians. Is this how we want to represent nutrition research?

I further sat and thought about this trial: even at the outset, given the design, and the quality of the proposed data to be collected, what could this have added to our knowledge of nutrition? The trial states that its goal was to conduct a randomized trial to compare low-carb versus low-fat diets on body weight and CVD risk factors in a diverse population without comorbidities. Beyond the overly reductionist paradigm of low-carb/fat, the study design is questionable in that “neither diet included a specific calorie or energy goal.” Ultimately, the trial tested whether a macronutrient goal, coupled with education and a meal replacement bar would spontaneously lead individuals to lose weight, in a diverse population without comorbid conditions. Not surprisingly, after being sent into an environment with highly palatable, minimally nutritious high carbohydrate/ high calorie foods, the low-carbohydrate group fared better. Is this substantially improving our understanding of nutrition and energy balance? If there’s any theme that holds true with weight loss and disease risk reduction, it’s that choosing a well-planned, reduced energy diet which an individual can adhere to is most important (4,5,6,7). Given the failure to reach recommended fiber intakes and minimal weight loss seen in this trial, nothing about the previous statement appears to change.

Even worse than the limited information to be gained from this kind of trial is the media reporting and subsequent public response to this research. The public’s perception of nutrition recommendations isn’t that great, as acknowledged in what I would argue is the most pertinent point of the Nutrition Research Priorities report:
“Perhaps the greatest barrier to advancing the connections between food and health is the variability in individual responses to diet; it is also the origin of public skepticism to acceptance of dietary advice….”
If individual variability spurs public skepticism, we should seek to explain that variability. One only needs to look to the original 1980’s Dietary Guidelines for Americans (4) to see that we’ve known that there is individual variation in weight gain/loss and in biomarker response to diets high/low in fat. Yet here we are, 3 decades later, and we’re conducting trials that do nothing to further isolate and understand the factors that contribute to this variation. However, what we are doing is deepening this public skepticism, as history shows us the controversial topic of low-carb vs. low-fat undoubtedly garners a lot of press.

Don’t get me wrong, research that attempts to understand individual variation in response to food and nutrients is being done, but, despite being identified as a major priority, it does not appear to be so. It’s truly a shame to be in this field and see examples of researchers employing the most cutting edge techniques to answer pressing questions, only to be overshadowed by overly simplistic paradigms that incite more sentiment than they do advance science. It is essential that scientists, and more importantly funding agencies, are aware of the field’s established research priorities, so that we can stop asking the uninformative questions that tantalize a public controversy and start generating truly substantial evidence, which fosters public trust in recommendations. These established Nutrition Research Priorities can be found in full here.

References:
1. http://www.ncbi.nlm.nih.gov/pubmed/24529976
2. http://www.ncbi.nlm.nih.gov/pubmed/23784071
3. http://annals.org/article.aspx?articleid=1900694
4. http://www.health.gov/dietaryguidelines/1980thin.pdf
5. http://www.nejm.org/doi/full/10.1056/NEJMoa022207
6. http://www.nejm.org/doi/full/10.1056/NEJMoa0804748
7. http://jama.jamanetwork.com/article.aspx?articleid=200094
8. http://www.health.gov/dietaryguidelines/1980thin.pdf

By Colby Vorland, Student Blogger

Could a “fatty intestine” be related to insulin resistance and energy balance? These and other provocative questions were addressed by Dr. Elizabeth Parks during ASN’s Scientific Sessions in San Diego. Organized by the Energy and Macronutrient Metabolism Research Interest Section, Dr. Parks gave a seminar titled, “Going with your gut: Individual responses in dietary fat absorption.”

Dr. Parks’ research often focuses on the cephalic phase of digestion – or the early physiological response before food is even ingested. She presented a story that led her to her current path: Teff and Engelman demonstrated in 1996 with a sham feeding model that taste has an important effect on glucose metabolism and, in 2002, Robertson and colleagues published data showing that, compared to a high fat meal, consuming a high carbohydrate meal at night resulted in better glucose tolerance in the morning. Concurrently, they demonstrated a high fat meal at night yields a better fat tolerance the following day. These data suggest that there is some adaptive priming occurring and that, as Dr. Parks put it, “you best metabolize what you’ve just eaten.” She noted that we need to better match the challenge test with the eating pattern of interest.

In 2003, Robertson and colleagues published the results of an experiment in 10 healthy participants scheduled for an endoscopy who were fed a high fat meal, then 5 hours later were fed 50 grams of fat with either 38 grams of glucose or water. The participants who consumed the glucose along with the fat in the second meal showed less lipid in the jejunum. In other words, some dietary fat was stored in the intestine from a meal and its release was accelerated when glucose in combination with fat was consumed. Since then, Dr. Parks and others have shown that simply tasting fat without ingesting it, or just consuming carbohydrate, can cause an early rise in chylomicron secretion and blood triglyceride levels. This means that the intestine stores some of the fat from previous meals; in fact, Parks estimates that ⅕ to ¼ of the fat in your meal is stored in the intestine for at least 16 hours, and it is released in response to taste. Their data also suggests that body fat is negatively correlated with the amount of fat coming from the intestine and entering the blood at a subsequent meal. If intestinal fat stores serve a regulatory function to control energy balance (by releasing in response to taste), this raises the possibility that the mechanism that controls how much is release is perturbed.

Parks then discussed research supporting that we can taste fat. As further evidence, they have scoured literature for kinetic data and devised a mathematical model to show that rate of release of fat from the gut is consistent with the idea that this physiological response is due to our ability to taste fat. She also noted that chylomicrons may be supported in the absence of dietary fat by fatty acids in circulation entering the enterocyte, being packaged into chylomicrons, and secreted. Some data suggest that high free fatty acids increase the contribution from plasma to chylomicrons.

Dr. Parks has also been asking: does the rate of fat absorption impact health? Dr. Jennifer Lambert and Parks have unpublished data showing that the time-course of triglyceride absorption between people can vary substantially – about 1 to 4 hours. She showed graphs of the fat absorption curves of individual participants, and the patterns were often variable, emphasizing that much remains to be understood about why this occurs. Finally, she showed that stratifying by an early or late absorption peak revealed differences in participants in each group. For example, participants with an early peak tended to be more insulin resistant than those with a later peak.

Dr. Parks has been innovative in her use of stable isotopes for exploring lipid metabolism in health and disease. Clearly the intestine is an underappreciated tissue in fat storage and we are just on the cusp of understanding the role in which it mediates health and energy balance.