A logical start when we think about nutrition is the mouth. The mouth is the first point of entry for all nutrients, in the form of the food we consume. Oral health and periodontal disease and their connection to nutrition run bi-directionally, where several studies have shown associations between individual micronutrients and periodontitis [1, 2]. Additional associations have been found between cumulative histories of oral problems including untreated caries, poor oral health, dental pain, restorations, extractions, use of prosthetics and food insecurity [3].

Periodontitis is defined as an inflammatory disease of the supportive tissues of the teeth caused by microorganisms which result in progressive destruction of periodontal ligaments and alveolar bone [4]. Periodontitis impacts 40-90% of the world’s population and is one of the most prevalent epidemics globally. Several micronutrients also impact periodontal health and include vitamin A (carotenoids, β-carotene), vitamin C (ascorbic acid), vitamin E (α-tocopherol), glutathione and melatonin [5,6]. These anti-oxidants have been shown to help overcome reactive-oxygen species mediated inflammation present in periodontal tissue which leads to periodontitis.

It is estimated that 15.8 million children under the age of 18 years in the United States live in households that are unable to access nutritious food necessary for healthy growth on a consistent basis [7]. In addition, over-nutrition in the form of childhood obesity and overweight, particularly among lower income children, is compounded by a preponderance to more cariogenic foods. A study conducted in Japan documented association between high body mass index (BMI) and increased risk of periodontal disease among young adults [8]. An abundance of fast food, poor quality, high sugar and simple carbohydrate-based diets in lower income neighborhoods predispose children to the development of plaque, dental decay and caries [9, 10]. Inadequate consumption of fruits and vegetables deprive children of the nutrients they need for healthy growth and development [10]. Proper oral health care started at a young age is essential to ensure good nutrition and oral hygiene into adolescence and adulthood.

Pregnant women are more prone to periodontitis, gingivitis and gingival hyperplasia. Increased secretion of estrogen during pregnancy has also been linked to periodontal disease during pregnancy [11]. Periodontal disease both during preconception and in pregnancy has been linked to adverse outcomes including premature birth, preeclampsia, gestational diabetes, fetal loss, small for gestational age babies [12]. Antioxidant rich foods consumed during pregnancy, in addition to diets high in fiber and low in refined sugar are important to prevent periodontal disease. Improved oral hygiene is also essential.

In America, life spans have increased by upwards of 30 years in the last century. It is estimated that by 2050, people will live to an average age of 100 [13]. The elderly, in addition to children and pregnant women, are also susceptible to the impacts of nutrition on oral health. Among this age group, compromised oral health care, due to age-related factors such as tooth loss, use of oral prosthetics, a lack of appetite and mastication ability, in addition to altered taste and gastrointestinal conditions, are important concerns. An inability to consume certain foods due to difficulties with chewing and swallowing can compound food insecurity [14, 15]. Oral care in the elderly and customized nutrition to account for their complex needs is essential to ensure good quality of life.

The link between good oral health and nutrition is undeniable and complex. It is time for more concerted efforts to be made to link the two interconnected areas of health, across the lifespan. Increased efforts to educate oral health providers on the importance of nutrition education, in addition to ensuring proper nutrition security for at risk groups, will ensure healthy bodies and wide toothy smiles!

 

References:

[1] Dommisch, Kuzmanova, Jonsson, Grant & Chapple. (2018). Effect of micronutrient malnutrition on periodontal disease and periodontal therapy. Periodontology 2000, 78, 129-153.

[2] Najeeb, S., Zafar, M.S., Khurshid, Z., Zohaib, S., & Almas, K. (2016). The role of nutrition in periodontal health: An update. Nutrients, 8, 530.

[3] Santin, G.C., Martins, C.C., Pordeus, I.A., & Ferreira, F.M. (2014). Food insecurity and oral health: A systematic review. Pesquisa Brasileira em Odontopediatria e Clinica Integrada, 144, 335-246.

[4] Newman, G.M., Takei, H.H., Klokkevol, R.P., Carranza, A.F. (2012). Carranza’s clinical periodontology. Classification of diseases and conditions affecting the periodontium. In Carranza’s Clinical Periodontology, 12th ed.; Michael, G.N., Henry, H.T., Perry, R.K., Fermin, A.C., Eds.; Elsevier: Amsterdam, The Netherlands, pp. 45-67.

[5] Garcia, J.J., Reiter, R.J., Guerrero, J.M., Escames, G., Yu, B.P., Oh, C.S., & Munoz-Hoyos, A. (1997). Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Letters, 408, 297-300.

[6] Najeeb, S., Khurshid, Z., Zohaib, S., & Zafar, M.S. (2016). Therapeutic potential of melatonin in oral medicine and periodontology. Kaohsiung Journal of Medical Sciences, 32, 391-396.

[7] Coleman-Jensen A, Gregory C, Singh A. (2014). Household Food Security in the United States in 2013. USDA ERS.

[8] Ekuni., D., Yamamoto, T., Koyama, R., Tsuneishi, M., Naito, K., & Tobe, K. (2008). Relationship between body mass index and periodontitis in young Japanese adults. Journal of Periodontitis Research, 43, 417-421.

[9] Moynihan P, Petersen PE. (2004). Diet, nutrition and the prevention of dental diseases. Public Health Nutrition, 7(1A):201-226.  Accessed 7/7/2015 at http://www.who.int/nutrition/publications/public_health_nut7.pdf.

[10] Edgar, W. (1993). Extrinsic and instinsic sugars: A review of recent UK recommendations on diet and caries. Caries Research, 27, 64-67.

[11] Hemalatha, V., Manigandan, T., Sarumathi, T., Aasthi Nisha, V., & Amudhan, A. (2013). Dental considerations in pregnancy – A critical review on oral care. Journal of Clinical Diagnostics Research, 7, 948.

[12] Ziegler, J., & Mobley, C.C. (2014). Pregnancy, child nutrition and oral health. Chapter 2: In Nutrition and Oral Medicine; Touger-Decker R., Mobley, C., & Epstein, J.B., Eds. Springer Science+Business Media, New York, pp. 19-37.

[13] Ham-Chande, R., (2005). Shapes and limits of longevity in Mexico. In proceedings of the living to 100 and beyond symposium, Orlando, FL, USA, 12-14 January 2005.

[14] Sheiham, A., & Steele, J. (2001). Does the condition of the mouth and teeth affect the ability to eat certain foods, nutrient and dietary intake and nutritional status amongst older people? Public Health Nutrition, 4, 797-803.

[15] Brodeur, J., Laurin, D., Vallee, R.,&  Lachapelle, D. (1993). Nutrient intake and gastrointestinal disorders related to masticatory performance in the edentulous elderly. Journal of Prosthetics and Dentistry, 70, 468-473.

According to the United Nations the aging population is growing and by 2050 the number of people aged 60 years old will reach 2 billion worldwide. With the aging population the prevalence of age-related disease is predicted to increase. An example of an age-related disease is neurodegeneration.  Dementia can be a result of several pathologies including increased levels of Lewy bodies (abnormal aggregates of protein in nerve cells), as seen in Parkinson’s disease.

Cerebrovascular disease is the second most common cause of dementia and is a result of  changes in blood flow to or within the brain. Blood flow in the brain can change because of hypertension, diabetes, smoking, and hypercholesterolemia. Patients with cerebrovascular disease experience cognitive impairment, specifically when trying to remember things or plan events/trips. It is important to note that symptoms can vary from patient to patient. A type of cerebrovascular disease is vascular cognitive impairment (VCI).

Nutrition is a modifiable risk factor for diseases of aging. As people age their ability to absorb nutrients from their diet decreases.  Several studies have reported that changes in B-vitamin absorption may play a role in the onset and progression of dementia. Additionally, a study by researchers in the United Kingdom shows that B-vitamin supplementation reduced brain volume loss in areas associated with cognitive decline. A recent international consensus statement from leaders in the field suggests that deficiencies in B-vitamin metabolism should be considered when screening dementia patients. My research using model organisms has tried to understand the disease processes associated with dementia.

Using a mouse model of VCI we have reported that deficiencies in folic acid, either dietary or genetic affect the onset and progression of VCI. Using the Morris water maze task we report that mice with VCI and folate deficiency performed significantly worse compared to controls. We assessed changes in the brain using MRI and interestingly found that folate deficiency changed the vasculature in the brains of mice with VCI. Because of either a genetic or dietary folate deficiency all the mice had increased levels of homocysteine.

Our results suggest that it is not elevated levels of homocysteine making the brain more vulnerable to damage, but the deficiency in folic acid, either dietary or genetic, that changes the brain. In the cell folic acid is involved in DNA synthesis and repair as well as methylation. These are vital functions for normal cell function. Therefore, reduced levels of folate may be changing the cells in the brain and making them more vulnerable to certain types of damage. We think that high levels of homocysteine may just be an indication of some deficiency (e.g. reduced dietary intake of folic acid). Maintaining normal levels of homocysteine are needed, since studies in humans have shown that elevated levels of homocysteine are a risk factor for neurodegenerative diseases and that reducing them is beneficial.

 

The popularity of the essential polyunsaturated omega-3 fatty acids (O3FA) is on the rise. In 2017, O3FA achieved a spot on the top 20 foods and ingredients list that Americans are adding to their diets (The Hartman Group). In addition, the global fish oil market is expected to reach a whopping 4.08 billion dollars in the next four years!  The proposed health benefits are likely the driving force behind the increasing demand.

Despite their booming popularity, a large percentage of adults are not meeting the O3FA recommended intake. There are three primary O3FAs with distinct characteristics: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although commonly grouped under the umbrella term O3FAs, are all O3FAs created equal?

Unique Characteristics of O3FAs

Omega-3 fatty acids cannot be sufficiently produced in the body earning them the title of “essential fatty acids.” The plant-derived omega-3, ALA, is the parent precursor to EPA and DHA. Unfortunately, the conversion rate in our bodies is very low.  It is important to realize that in the process of metabolizing ALA to EPA and DHA, a series of anti-inflammatory markers are produced (leukotrienes, prostaglandins and thromboxane). As these anti-inflammatory metabolites are beneficial, direct EPA and DHA consumption is needed to meet bodily requirements.

Independent and Complementary Health Benefits

The majority of current research focuses on the health benefits of marine fatty acids.  DHA and EPA consumption portray an array of shared and complementary benefits related to the treatment of cardiovascular disease, depression diabetes, sleep disorders and more. DHA is more significantly associated with decreases in resting heart rate, blood pressure and with improvements in cellular membrane health due to its additional double bond and longer carbon chain. Increased cellular levels of EPA have been shown to benefit coronary heart disease, hypertension and to decrease inflammation. EPA and DHA are both associated with reduced gene expression related to fatty acid metabolism, reduced inflammation and oxidative stress.

Specific supplementation of ALA is not consistently associated with cardiovascular health. Although plant-derived ALA can be easily substituted in for excess omega-6 fatty acids (O6FAs). Research has shown that by reducing the O3FA:O6FA ratio, you can decrease bodily inflammation, increase anti-inflammatory markers and more efficiently utilize EPA and DHA.

An ALA, EPA and DHA-Rich Diet

The 2015-2020 Dietary Guidelines for Americans recommends that healthy adults consume at least 8 ounces of a variety of non-fried fatty seafood per week. For EPA and DHA requirements, the American Heart Association recommends fatty marine sources containing 500 mg or more of EPA and DHA per 3oz cooked serving (e.g., salmon and tuna).   ALA is the most commonly consumed O3FA in the Western diet as it is found in plant-based foods (e.g., dark green leafy vegetables, walnuts, canola oil, flax seed). Unlike EPA and DHA, an Adequate Intake (AI) level is established at 1.6 g/day and 1.1 g/day for men and women respectively.

The Final Verdict 

The wide range of benefits stemming from marine O3FAs indicates the importance of regular consumption of fatty seafood and EPA and DHA-containing products.  The incorporation of plant-derived ALA may serve more importantly as a substitute for omega-6 fatty acids to reduce bodily inflammation, decrease the high O3FA:O6FA ratio typically observed in the Western diet, and to help elevate EPA and DHA levels in the body. EPA and DHA may be featured as the health promoting “dynamic duo,” but ALA is still invited to the party!

 

References

1.         Yanni Papanikolaou JB, Carroll Reider and Victor L Fulgoni. U.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003–2008. Nutrition Journal 2014.

2.         Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, Cunnane SC, Holden JM, Klurfeld DM, Morris MC, Whelan J. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr 2009;139(4):804S-19S. doi: 10.3945/jn.108.101329.

3.         Frits A. J. Muskiet MRF, Anne Schaafsma, E. Rudy Boersma and Michael A. Crawford. Is Docosahexaenoic Acid (DHA) Essential? Lessons from DHA Status Regulation, Our Ancient Diet, Epidemiology and Randomized Controlled Trials. Journal of nutrition 2004;134.

4.         Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 2012;142(3):614S-25S. doi: 10.3945/jn.111.149633.

5.         Bork CS, Veno SK, Lundbye-Christensen S, Jakobsen MU, Tjonneland A, Schmidt EB, Overvad K. Dietary Intake of Alpha-Linolenic Acid Is Not Appreciably Associated with the Risk of Ischemic Stroke among Middle-Aged Danish Men and Women. J Nutr 2018. doi: 10.1093/jn/nxy056.

6.         Evangeline Mantzioris MJJ, Robert A Gibson and Leslie G Cleland Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr 1995;61:320-4.

7.         Agriculture. USDoHaHSaUSDo. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. December 2015.

By: Nafisa M. Jadavji, PhD

 

A stroke occurs when there is reduced blood flow to the brain. Blood carries oxygen and glucose to cells in the brain. When there are reduced levels of blood, these cells start to die. Since the brain controls behavior, this cell death leads to impairments in function. The impairments are dependent on where the stroke happens in the brain. There are two main types of stroke: hemorrhagic and ischemic. For this blog, I will be focusing on ischemic stroke which is a result of blockage in a blood vessel. Currently, stroke typically affects older individuals and the global population is aging according to the United Nations. Additionally, older individuals also lose their ability to absorb all the vitamins and nutrients they require from their diet as they age.

Nutrition is a modifiable risk factor for diseases of aging. For example, B-vitamin absorption decreases as individuals age. B-vitamins play a major role in reducing levels of homocysteine, a non-protein amino acid. High levels of homocysteine have been associated with increased risk to develop cardiovascular diseases, such as stroke. Supplementation with B-vitamins has been reported to have positive effects on brain health.

A study by researchers in Oxford University and University of Oslo has shown that B-vitamin supplementation in the elderly within the United Kingdom reduced age-related brain atrophy after 2 years of supplementation. Furthermore, another study by the same group reported that B-vitamin supplementation reduced cerebral atrophy in areas vulnerable to Alzheimer’s disease.

More recently, a group from China reported that folic acid supplementation in combination with Enalapril, used to treat heart disease, reduced the risk of stroke by 21% in patients that were hypertensive.

Within the aging population, B-vitamin supplementation has been reported to have positive effects on brain health. The elderly are more prone to ischemic stroke, but the mechanisms through which this benefit is accomplished are not well understood.

A recent study investigating the role of B-vitamin supplementation on ischemic stroke was published in the Neurobiology of Disease. This study tried to examine the mechanisms of how supplementation improved brain function. A group of wildtype males were put on a folic acid deficient diet (0.2 mg/kg) prior to ischemic damage to increase levels of homocysteine and another group of mice were put on a control diet (2mg/kg folic acid). After ischemic damage to the sensorimotor cortex, FADD mice were put on a supplemented diet, where levels of folic acid, riboflavin, vitamin B12, and choline were increased. Animals were maintained on the diets for 4-weeks after which motor function was assessed.  Researchers found that supplemented diet mice performed better on motor tasks compared to CD mice with ischemic damage. In the brain tissue, increased levels of plasticity and antioxidant activity were reported.

Combination therapies for stroke-affected patients are thought to be most effective. A pharmaceutical in combination with a lifestyle change, such as increased exercise may be beneficial for stroke-affected patients. This data suggests that nutrition may also be a viable option to prevent or attenuate ischemic damage.

 

 

Omega-3 fatty acids have been long touted for their cardiovascular benefits. But many research studies strongly suggest that these fatty acids exert improvements well beyond those related to heart health.

 

Omega-3 fatty acids and/or fish oil supplements (the latter being a rich source of omega-3s) have been administered to those with cancer, heart disease, rheumatoid arthritis, and psychiatric disorders (i.e. schizophrenia and major depressive disorder) with resultant improvements in disease-specific outcomes and body composition (read: more and/or better quality of muscle) (1, 2). The supplement also has essentially no side effects, aside from the occasional lingering fishy after-taste. It’s thought that these beneficial effects are due to omega-3’s inhibition of numerous pro-inflammatory pathways.

So is there a place for these supplements in healthy populations? Say, exercising older adults? This is exactly what Mariasole Da Boit and a group of colleagues investigated in a randomized, double-blind placebo controlled trial published in the American Journal of Clinical Nutrition earlier this year (3). Fifty men and women (age 70.6 ± 4.5) participated in a resistance exercise training program for lower limbs twice weekly for 18 weeks. All were randomized to 3g fish oil/day or placebo (3g safflower oil/day). In women, maximal isometric torque (static contraction) and muscle quality defined by torque per unit of muscle cross-sectional area improved more in the fish oil group, independent of muscle mass changes; no differences were observed in men. Plasma triglycerides decreased in both sexes, while maximal isokinetic torque (moving contraction), 4-minute walk test, chair-rise time, muscle size, and muscle fat did not differ. The authors speculate that omega-3 improves neuromuscular function and/or enhances the contractile properties of type II (fast-twitch) muscle fibers. Some findings suggest that older women do not increase muscle strength to the same degree as older men; thus women could undergo a more profound response to resistance training since there is a greater capacity for muscular improvement.

While this is only one study and the mechanisms behind the results are somewhat speculative, the results are promising. With forthcoming research, omega-3 fatty acid supplements might become an evidence-based recommendation for healthy community-dwelling older adults and many clinical populations.

  1. Lee S, Gura KM, Kim S, Arsenault DA, Bistrian BR, Puder M. Current clinical application of omega-6 and omega-3 fatty acids. Nutrition in Clinical Practice 2006; 21(4):323-41
  2. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 2011;117(8):1775-82.
  3. Da Boit , Sibson R, Sivasubramaniam S, Meakin JR, Greig CA, Aspden RM, et al. Sex differences in the effect of fish-oil supplementation on the adaptiveresponse to resistance exercise training in older people: a randomized controlled trial. American Journal of Clinical Nutrition 2017; 105:151-8

Many dangerous fad diets exist that purport to treat diseases such as cancer by manipulating the pH of blood with different foods. While there is no good evidence that acidic foods alter the body’s pH and promote disease, the hypothesis that “dietary acid load” relates to disease should not be completely dismissed. The kidney serves to regulate blood pH, but if kidney function declines and other tissues catabolize to maintain pH, then it is very plausible that manipulating the diet to reduce the acid load could spare tissues and improve outcomes in chronic kidney disease (CKD). After all, for example, the metabolism of amino acids yields hydrogen ions, whereas fruits and vegetables contain organic salts that generally reduce acid load when metabolized. Recently, a growing number of human studies that manipulate diet acid load using fruits and vegetables and sodium bicarbonate support this hypothesis. Let’s take a look at some of them.

The first randomized controlled trial on bicarbonate supplementation and CKD progression was published in 2009 by de Brito-Ashurst and colleagues. Bicarbonate is produced by the kidneys and serves to neutralize acid. Supplementation of bicarbonate for 1 year in CKD patients slowed the progression of kidney disease as suggested by creatinine clearance and reduced the need for dialysis. The next year, in 2010, a 5-year trial was published by Donald Wesson’s group that found a slowed kidney decline as measured by estimated glomerular filtration rate (eGFR) with bicarbonate supplementation. Several subsequent studies by his group have used bicarbonate or fruits and vegetables to achieve beneficial outcomes. Goraya et al. gave oral bicarbonate or enough fruits and vegetables that were estimated to reduce dietary acid load by 50% to CKD patients for 30 days and also observed a slowed reduction in eGFR in patients at moderate, but not mild, stages of the disease. In patients with more advanced stages of CKD, one year of bicarbonate or fruits and vegetables did not slow the decrease in eGFR, though several urinary markers of kidney injury were reduced. Their most recent trial tested if kidney function might be preserved through a reduction in angiotensin II in moderate stage CKD patients. Three years of bicarbonate or increased fruits and vegetables lessened the decline in eGFR and resulted in a corresponding decrease in the marker angiotensin II. Other studies using bicarbonate from six months to two years have provided strong evidence that reducing acid load consistently slows the decline of eGFR, and improves markers of bone health and muscle function.

Each of the studies described provided fruits and vegetables to patients free of charge to increase adherence. It will be important to test if adherence can be maintained through education alone. Additionally, it may be that “prescribing” fruits and vegetables is effective at improving outcomes and reducing health care costs more so than bicarbonate since they also reduce blood pressure. While “alkaline diets” in general should be viewed skeptically, there is accumulating evidence that fruits and vegetables as dietary alkali do indeed help in kidney disease.

By Caitlin Dow, PhD

The most recent data from the CDC indicates that approximately 35% of American adults have obesity (1). In order to reduce obesity prevalence, a popular notion is that people with obesity just need to “eat less and move more.” Indeed, many public health programs use this concept as their primary approach for combating obesity. While eating less and moving more may help prevent obesity or result in successful, sustained weight loss in individuals who are simply overweight (but not yet obese), ongoing research indicates that these simple lifestyle changes will do very little in the face of prolonged obesity (2).

If you look at any weight loss study, you will most assuredly find the same results, regardless of study design. The first six months are generally characterized by substantial weight loss, followed by sustained weight regain, resulting in a final weight that is negligibly lower and potentially higher than the starting weight . This “checkmark effect” or weight loss recidivism that has been reported nearly ubiquitously across diet and exercise-based weight loss trials (3) indicates that lifestyle interventions are generally not successful modalities for treating obesity.

Based on a rudimentary understanding of metabolism, the calories in/out approach should work for weight loss and weight loss maintenance. So why doesn’t it work for so many people? The answer lies in the complex network linking the environment, genetic predisposition to obesity, as well as metabolic and physiological changes. A large body of literature indicates that the brain’s reward systems are significantly dysregulated in individuals with obesity (4). In an environment that supports ease of access to highly palatable foods, the pleasurable effects of consuming said foods can override homeostatic control of intake. While some people are able to regulate intake despite the high palatability of these foods, a number of genetic mutations in the brain’s reward systems may result in overeating and obesity in many people. Furthermore, the hypersensitive reward systems that often lead to obesity can become insensitive once a state of obesity is attained. In effect, this leads to overeating to receive the same pleasure from the same foods. These dysregulated reward systems are coupled with preadipocyte expansion into mature adipocytes, allowing for increased fat storage. While this isn’t the entire story, this should shed some light on the complex interactions of dysregulated internal systems that foster the metabolic abnormalities that result in obesity. Importantly though, these impairments are typically only demonstrated once obesity has been introduced and sustained (3).

As for weight loss, when caloric restriction is initiated, the body triggers a number of systems to prevent starvation. From an evolutionary perspective, this makes sense as food sources were often unpredictable and the body adapted to conserve energy – the “feast and famine” principle. However, for most of us living in industrialized nations, famine is rare and feast is common, limiting the need for this once very necessary adaptation (though the body has not evolved to recognize the abundance of calories in our modern food supply). When we try to induce weight loss via caloric restriction, the body will reduce its resting metabolic rate to counter these advances (5). This supports the “set point theory” – the idea that the body will defend its highest-sustained weight. In fact, as weight loss increases, the drive to restore the highest bodyweight only increases (6). It’s like when you’re pulling on your dog’s leash to get him into the vet and he plants his feet firmly and resists with all his might. Ultimately his strength pulls him out of his collar and sends him running in the opposite direction. Except here we’re talking about the human body and it’s not nearly as comical.

All of these biological adaptations that introduce, sustain, and defend obesity explain why weight loss and its maintenance is so exhaustingly difficult for so many people. As Ochner and colleagues suggest, most individuals who had obesity but lost weight simply have “obesity in remission and are biologically very different from individuals of the same age, sex, and body weight who never had obesity.” As a hypothetical scenario, imagine you are comparing two people: they weigh the same, but person A had obesity and has lost weight whereas person B has never lost weight. Person A will have to burn up to 300 calories more (or consume 300 calories fewer) than person B to maintain that weight (2). This underscores the idea that weight regain is not simply an issue of willpower and weakness.

What we need more of are studies evaluating multiple approaches to weight loss (surgeries, medications, likely in combination with lifestyle changes). What we need less of is bias from people without obesity, the media, and even healthcare providers. Indeed, “the mere recommendation to avoid calorically dense foods might be no more effective for the typical patient seeking weight reduction than would be a recommendation to avoid sharp objects for someone bleeding profusely” (2). We also need better obesity prevention approaches because, clearly, it’s biologically more feasible to prevent weight gain than to lose weight and keep it off.

References

1.Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adults obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814. doi:10.1001/jama.2014.732.

2.Ochner CN, Tsai AG, Kushner RF, Wadden TA. Treating obesity seriously: when recommendations for lifestyle change confront biological adaptations. Lancet Diabetes Endocrinol. 2015:

3.Ochner CN, Barrios DM, Lee CD, Pi-Sunyer FX. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol Behav. 2013:120:106-13. doi: 10.1016/j.physbeh.2013.07.009.

4.Kenny JP. Reward mechanisms in obesity: new insights and future directions. Neuron. 2011:69(4):664-79. doi:10.1016/j.neuron.2011.02.016

5.Grattan BJ, Connolly-Schoonen J. Addressing Weight Loss Recidivism: A Clinical Focus on Metabolic Rate and the Psychological Aspects of Obesity. ISNR Obesity. 2012. doi:10.5402/2012/567530

6.Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes.2010:34:S47-55. doi:10.1038/ijo.2010.184

By Allison Dostal, PhD

Gastrointestinal problems are one of the most common unpleasant issues that we all experience at some time or another. But what if your upset stomach wasn’t just a passing discomfort? What if severe abdominal pain, cramping, fatigue, and diarrhea became more of your norm and less of a passing annoyance? For more than 1.4 million Americans, these symptoms typify their experience with inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the gastrointestinal (GI) tract. The specific cause (or causes) of IBD remain unknown, but one leading hypothesis is that the bacteria that inhabit our GI system – termed the gut microbiome – play a central role. In this post, we’ll take a closer look at this condition and highlight research aimed at elucidating the impact of the microbiome in IBD development, progression, and treatment.

Characteristics, Diagnosis, and Treatment of IBD

Inflammatory bowel disease is unique in that its symptoms vary from person to person, and an individual’s own experience with their condition can differ markedly from another affected person. Most people are diagnosed with one of the two most common types of IBD, which are ulcerative colitis (UC) and Crohn’s disease (CD). The primary distinguishing factor between the subtypes is that in UC, symptoms are limited to the colon. In contrast, any part of the GI tract – from the mouth to the anus – can be affected in CD. In addition, UC only involves the innermost layer of the colon, while CD can extend deeper into the cell layers of the GI tract. Lastly, in CD, the inflammation can “skip”, leaving normal areas between patches of affected GI tract.

Making a clear IBD diagnosis isn’t always as easy as meeting – or not meeting – these criteria. There is no gold standard available for a clear-cut diagnosis, and 5-15% of cases do not meet strict criteria for either UC or CD. These patients fall into the “IBD type unclassified” (IBDU) group. And in up to 14% of patients, the diagnosis changes over time. Despite the difficulty in specific diagnosis, all subtypes of IBD have one strong feature in common: an abnormal response by the body’s immune system. The immune system is composed of various cells and proteins that usually protect our bodies from infection. However, in people suffering from IBD, the immune system reacts inappropriately, and mistakes benign or beneficial cells and bacteria for harmful foreign substances. When this happens, the immune system produces an inflammatory response within the GI tract and produces the symptoms of IBD. This adverse reaction is termed a “flare”, and can result in symptoms such as abdominal pain and cramping, diarrhea, fever, and blood in the stool. People with IBD often have deficiencies in vitamins, minerals and macronutrients stemming from loss of appetite, reduced food intake, and malabsorption from the GI tract. The lack of nutrients can lead to worsening of symptoms or development of new complications.

Treatment for IBD is centered around two goals: achievement of remission and prevention of flares. Anti-inflammatory drugs such as aminosalicylates and antibiotics are often the first line of treatment, and can be followed by corticosteroids, immunomodulators, and/or biologic agents. In severe cases, removal of the affected part of the GI tract is needed if a patient is not responsive to other treatments.

The Role of the Microbiome in IBD

In recent years, it has become clear that the microbes in our gut have a key role in IBD, but the bacteria involved and their associated functions remain largely unknown. An imbalance of the normal gut bactera due to loss or overabundance of certain species is important in the persistence of the inflammatory responses seen in IBD. The role of the gut microbiota in IBD pathogenesis has been demonstrated by studies showing that antibiotic use can reduce or prevent inflammation – antibiotics work by reducing the number and types of bacteria found in the gut, therefore killing microbes that are causing IBD symptoms. Also, results from studies with UC patients who underwent a transfer of stool collected from healthy donors – called a fecal microbiota transplant – had notable disease remission. However, results have not been consistent between studies, due to differences in populations studied, official diagnosis, treatment methods and doses, and methods of assessing study endpoints. Therefore, no consensus on the microbiome’s relationship to IBD has been reached.

Research Endeavors

As you can imagine, the combination of unpleasant, potentially severe symptoms and an uncertain diagnosis or treatment can result in significant stress on IBD sufferers, their caregivers, and health care providers. The scientific efforts dedicated to identifying causes and cures for IBD have rapidly expanded in recent years due to advances in technology that allow researchers to work toward refining a clear diagnosis, map specific gut bacteria associated with disease development and symptoms, and identify defined targets for therapy. One of these initiatives is the Crohn’s and Colitis Foundation of America (CCFA) Microbiome Initiative, which is dedicated to understanding the role of the gut microbes in IBD, IBD families, and disease flares. Thus far, there are 7 active projects and 30 published manuscripts stemming from the Initiative, which have determined that different subsets of IBD are characterized by signature bacterial compositions and that people carrying different IBD genes have different microbiome compositions, among other accomplishments.

Other organizations are also supporting IBD research endeavors, including the Kenneth Rainin Foundation, whose Innovator Awards program provides $100,000 grants for one-year research projects conducted at non-profit research institutions, and the NIH’s Human Microbiome Project, which has funded several projects aimed at genetic and metabolomic elucidation of risk for Crohn’s disease. Several randomized trials are ongoing at this time, and their results will inform future directions for diagnosis, treatment, and eventual resolution of IBD.

References

Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol.2004;38(6):475–483.

Bull MJ, Plummer NT. Part 1: The Human Gut Microbiome in Health and Disease. Integr Med. 2014 Dec; 13(6):17-22.

Crohn’s and Colitis Foundation of America:http://www.ccfa.org/

Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease.J Clin Microbiol. 2005;43(7):3380–3389.

Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives. World J Gastroenterol. 2015 Jan 7;21(1):21-46.

By Allison Dostal, PhD, RD

The relationship between nutrition and health is fully entrenched in the mainstream media – everyone from career scientists to our next door neighbor seems to be an expert on the topic. Trained health professionals and researchers do our best to deliver credible information, but it’s all too easy for clear messages to get lost in the constant stream of 30-second sound bites.

Dr. Andrew Brown, a Scientist with the University of Alabama-Birmingham’s Nutrition Obesity Research Center (NORC) & Office of Energetics, is focusing his current work on illuminating common misconceptions in the field of nutrition and increasing awareness of media perspectives and biases. I recently had the opportunity to ask him a few questions related to research integrity, science communication, and being a part of the next generation of nutrition researchers and educators working to effectively deliver nutrition information in the Digital Age.

Tell us about your work with NORC and the Office of Energetics.

The majority of my work is in the field of meta-research, which can involve investigating what was studied, why it was studied, and how it was studied. In addition to the more common forms of meta-research, like systematic reviews and meta-analyses, I look at the way that research is conducted, the quality of reporting, analytical choices during statistical analysis, and from where nutritional zeitgeist comes despite little strong empirical evidence.

How did you become interested in calling attention to myths, presumptions, and reporting accuracy of nutrition research?

As a student studying lipid chemistry, I noted that most lipid biochemists (as well as many others) recognized that dietary cholesterol had little impact on blood cholesterol, and yet cholesterol-containing foods were demonized. During my doctoral degree, I attended the Office of Dietary Supplements’ Research Practicum, where I anticipated learning what was and was not known about the health impacts of dietary supplements. Instead, and to my benefit, much of the talk was about limitations of current research, regulatory limitations, and differences in philosophies about how diet – and particularly supplements – could be studied. Claims about dietary cholesterol and supplements are just some of the dietary beliefs that are either completely refuted by our best science or at best weakly supported; yet, many people within and beyond the nutrition science community believe them. Thus my interest is at least two fold. The first is trying to determine which beliefs I hold that are not supported by the evidence, such as the relationship between eating/skipping breakfast and obesity. The other is to help communicate the state of science to hopefully decrease confusion.

With the attention that your research group is calling to this movement, how do you see publication and the media’s attention to nutrition changing in the next 5-10 years?

I am optimistic that nutrition science will continue to improve, including more discussions of the nuances of nutrition science rather than speaking in absolutes. If we ‘know’ that sugar is bad, or polyunsaturated fats are good, or that breakfast prevents obesity, then there is nothing left to study. Because of human heterogeneity within ever-changing local and global environments, it is unlikely that there is one diet or one set of recommendations that is appropriate for everyone and every situation, even for essential nutrients. Population-level recommendations are great place-holders until we develop more refined recommendations for individuals, subgroups, food-types, food-compositions, and other aspects of diet.

In a recent ASN blogger interview with Paul Coates, the Director of the NIH Office of Dietary Supplements, he stated with regard to the aging of the nutrition researcher population, “A fairly urgent challenge is identifying people who can come up behind us and continue to identify opportunities for research—particularly those that have public health implications— and be committed to help tackle them.” What are your thoughts on strategies for engaging young nutrition researchers in scientific discourse? How can young researchers take part in a dialogue with fellow scientists, the media, and the public to improve communication and perception of nutrition research?

I think we need to keep our eyes open for promising individuals that we can trust to think scientifically and ethically, and help them grow in a tailored way. The increased use of Individual Development Plans seems to be a great step in this direction, as is putting a maximum number of years on post-doctoral training, with the idea that a post-doctoral position is for additional training, not for an indefinite job. I have been extremely fortunate to have had mentors that gave me opportunities to speak, develop ideas, and truly contribute to teams and discussions throughout my formal education, as early as my freshman year. I was encouraged to write grants, publish, and complete other essential activities in the business of science, but my mentors focused very much on teaching me how to ask scientific questions; read the existing literature; develop critical scientific thinking skills; communicate with precision; and conduct good science.

On the side of mentees and students, I think it is important to be inquisitive while being willing to admit if you don’t know something. Stating confidently something that is false is a great way to lose trust and be excluded from the discussion. Instead, ask for clarification; add information to the conversation that might be useful; and, most importantly, don’t force yourself into discussions just to be noticed.

I also think it is important to move away from research focusing so heavily on public health (with the full disclosure that I work in a School of Public Health). Improvements in the public’s health is a noble and lofty goal, but to come into a study with the assumption that the outcome will result in an improvement in public health (particularly the entire population’s health) encourages overstating of results, misinterpretation of data, and doubling-down on dietary preconceptions. In science, the focus needs to be on determining some form of objective truth or lawful relationship. If we can identify these truths and relationships, then ways to improve public health will become self-evident, with the understanding that policy decisions are based on value structures beyond scientific evidence.

What advice do you have for graduate students and early career investigators?

Make sure you are doing something you love, that you do it to the best of your ability, and that you do it with the highest integrity. Be sure anything you put your name to is something that you are willing to take credit for, but also understand that this means you will be responsible for shortcomings of the work if problems are discovered later. And always be willing to entertain and evaluate an idea, especially one you disagree with or find unpalatable; these could be the very ideas that lead you to new lines of work, may help you better communicate your ideas to those who disagree with you, or might even overturn your entire view on a subject. As Aristotle said, “It is the mark of an educated mind to be able to entertain a thought without accepting it.”

By Kevin Klatt

Colorectal cancers are the third most common worldwide, and represent one of the major areas of prevention research. Rates of these cancers increase with industrialization, and are uncommon in Africa and much of Asia. A number of potential nutritional targets have been posited, based on preclinical and epidemiological data; however, these remain controversial. The American Institute of Cancer Research’s 2011 report (1) on Colorectal Cancer states that there is convincing evidence that foods high in fiber decrease risk and red and processed meats increase risk of colon cancer. However, there are few controlled feeding studies in humans have corroborated these associations; indeed, a large body of literature (2-7) focusing on dietary fiber supplementation back in the late 90’s and early 2000’s did not show any support for any positive effects of high fiber/low-fat diets on recurrent adenomas . However, these studies can/have been criticized for: 1. not being long enough 2. fail to capture of a window of true prevention (as subjects already had adenomas) 3. The dose/type of fiber. Since these trials, considerable experimental data (8,9) has been generated to suggest that the type of fiber, its dose, and the type/amount of short chain fatty acid fermentation products likely add some complexity to the inconsistent epidemiological associations between fiber intake and colorectal cancer risk.

A recent study published in Nature Communications (10) provides a novel perspective on this contentious topic of high-fiber diets and colon. The study employed a food-based dietary intervention in 2 populations: African Americans and rural South Africans (a sensible population to study given Burkitt’s original observations that rural Africans are nearly free of large bowel diseases). Twenty healthy, middle-aged African Americans and 20 rural Africans were first examine in their home environments for 2 weeks, to examine their normal food intake, before being housed in their respective research facilities for the 2 weeks of the dietary intervention (to ensure compliance). African Americans were given the ‘African style’ diet that was low in fat (16% kcals) and high in fiber (55g/day). Participants from Africa were given a western style diet that was higher in fat (52% kcals) and lower in fiber (12g/day). Notably, the high fiber diet was achieved using HiMaize, a purified resistant starch product. The authors look at outcomes related to mucosal epithelial cell proliferation (Ki67 staining) and markers of inflammation (CD3+ intraepithelial lymphocyte and CD68+ lamina propria macrophage staining), to examine the effect of diet on predicted neoplastic change and increased risk of colon cancer. They further look at alterations in microbial composition, highlighting changes in microbes with the baiCD gene, responsible for the deconjugation of bile acids and production of their carcinogenic, secondary metabolites. Their results quite nicely show that the high fiber intervention alters biomarkers in directions that suggest a protective effect against colorectal cancer, while also finding some interesting nuances related to amino acid and choline metabolism.

While providing encouraging results for the role of nutrition in colorectal cancer development, the study leaves us with more hypotheses to test, and a renewed interest in the way in which fiber and its fermentative products might act to buffer against colorectal cancer. Without hard clinical outcomes, it’s difficult to get too excited about the results in light of the multiple fiber interventions that have failed in the past. The biomarkers chosen are not without their scrutiny, as it has been noted that decreases in apoptosis rather than increased cell proliferation better predict tumorigenesis in animal models of colorectal cancer (11). Regardless of one’s enthusiasm about biomarker changes over 2 weeks, it does force us to critically think about previous study designs that have cast doubt on fiber’s role in colon cancer. The authors in this current study employ highly butyrogenic starches, at doses not tested in the trials that have failed before. There is consistent molecular evidence that butyrate works in a paradoxical manner, both stimulating cell proliferation at low concentrations and inhibiting it at high (12), leaving open the possibility that the previous doses of fiber were too low to see a beneficial effect.

Given the Western diets low concentrations of dietary fiber, particularly resistant starches (13), as well as the increased enthusiasm to fortify the food supply with added fibers, further research examining the role of particular fibers, their appropriate doses, and their relationship to clinical outcomes appear warranted. The type 2 resistant starch utilized in this study is uncommon in the food supply, coming largely from raw potatoes, unripe bananas, and some legumes and represents a potential area for food technologists to significantly alter the food supply for better health (14).

References
1. http://www.aicr.org/continuous-update-project/colorectal-cancer.html
2. http://www.ncbi.nlm.nih.gov/pubmed/11073017
3. http://www.ncbi.nlm.nih.gov/pubmed/10770979
4. http://www.ncbi.nlm.nih.gov/pubmed/10770980
5. http://www.ncbi.nlm.nih.gov/pubmed/7730878
6. http://www.ncbi.nlm.nih.gov/pubmed/7473832
7. http://www.nejm.org/doi/pdf/10.1056/NEJM199901213400301
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926973/
9. http://www.ncbi.nlm.nih.gov/pubmed/20937167
10. http://www.nature.com/ncomms/2015/150428/ncomms7342/full/ncomms7342.html
11. http://carcin.oxfordjournals.org/content/18/4/721.abstract
12. http://jn.nutrition.org/content/134/2/479.full
13. http://linkinghub.elsevier.com/retrieve/pii/S0002-8223(07)01932-3
14. http://advances.nutrition.org/content/4/3/351S.full