Based on a presentation to the New York Academy of Sciences on December 4, 2015.
Much of what I write in my newsletters and social media posting relate to the latest science in nutrition, weight regulation and the gut microbiome.
I was invited by the Sackler Institute for Nutrition to lecture at the New York Academy of Sciences at their symposium on Managing Disease-Related Lean Body Mass Loss through Clinical and Nutrition Interventions. The goal of the symposium was to present cutting-edge nutrition science on the prevention and mitigation of lean body mass losses in illness by strategic nutrition interventions.
I was charged with the task of discussing how nutrition may impact the development and course of chronic disease. Below is my symposium abstract.
The Impact of Nutrition in the Management of Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory gastrointestinal (GI) tract disorder which can be associated with diminished nutrient intake and absorption causing malnutrition, having an adverse impact to the patient. Assessment of nutritional status should be conducted on all patients with IBD as the prevalence of nutritional deficiencies and malnutrition in IBD are quite common and nutrition intervention may improve disease activity, mitigate symptoms and improve quality of life. Lean muscle mass depletion from systemic inflammation relates to disease activity in IBD and should be minimized. Augmenting nutritional status prevents adverse health consequences of malnutrition in patients with IBD and controls the underlying course of disease. This lecture will review the prevalence and pathophysiology for the depletion of lean muscle mass and nutritional deficiencies in IBD with evidence for central parenteral nutrition (CPN), enteral nutrition, dietary (elimination diets, low carbohydrate diet, low fermentable oligo-, di-, monosaccharide and polyol [FODMAP], fiber, omega-3-fatty acids). Micronutrient deficiency should be investigated and rectified. Enteral nutrition can induce and sustain remission in Crohn’s disease. CPN is indicated in the setting of proven intestinal failure. Ω3 fish oil, prebiotics and glutamine do not have sufficient evidence to support their use in the treatment of active IBD.
Below is a summary of my presentation to the New York Academy of Sciences. I was honored to be enrolled as a member of the organization after my presentation. The accompanying slides are available here.
Chronic Disease in the US and World-Wide. Prevalence, Long-term Consequences and Economic Impact of Chronic Diseases.
What ultimately causes us to become disabled, suffer a poor quality of `life or die? Chronic diseases constitute a major threat to our quality of life and economic well-being. Chronic diseases are long-term diseases that are not contagious and largely preventable. They include diseases such as obesity, diabetes, cardiometabolic disorders, cancer, dementia, autoimmune diseases and many more, which imparts a growing burden for society. Chronic diseases account for 60% of deaths worldwide. In 2000, 125 million (M) Americans had an identifiable chronic disease with a projected prevalence of 171in 2030.
Every 7 out of 10 natural deaths in the U.S. are caused by one or more chronic diseases. Of the total spending on public and private health care in the U.S. approximately $2 trillion in 2005, more than 75% went toward treatment of chronic disease with 191B devoted to obesity and its consequences.
In 2008, the chronic disease almanac reported that in 2003 the heaviest concentration of chronic diseases were in the mid-Atlantic and South Eastern United States. They also observed that the prevalence of chronic pulmonary disorders was surprisingly high (49.2M), while hypertension 36.7M, mental disorders 30.3M, cardiovascular diseases (CVD), (19.1M), cancer (10.5M), diabetes (13.8M) and stroke (2.5M) had far-reaching adverse health and economic outcomes. In 2002, CVD by far was the most common cause of death, however today, cancer is edging out CVD for the leading cause of mortality world-wide. Arthritis (53M) is the most common cause of disability among the chronic diseases.
Pathogenesis of Chronic Disease
The pathogenesis of chronic diseases is a complex web of dynamic interactions between genetics risks that are modifiable by environmental factors and how they impact upon the gut microbiota which in turn influences genetic expression.
Tobacco use, alcohol consumption, diet, environmental toxins, physical activity, stress, body weight and morphology all have influence over the triad of genetics-gut microbiome-inflammatory response model.
One common myth is that those who are overweight or obese are “overnourished”. That is furthest from the truth. In fact, obesity is a form of malnutrition that is spreading worldwide whereby the prevalence of obesity equals undernutrition aka malnutrition (33%).
The approaches to nutrition intervention to prevent and treat chronic disease need to encompass the common threads of the underlying pathophysiology of disease that portend towards unremitting inflammation.
Chronic uncontrolled systemic inflammation is the root cause for the onset and progression of chronic degenerative diseases. Harmful and damaging enzymes and mediators released from activated immune cells degrades the body’s healthy tissues, promotes glucose intolerance and fat accumulation, plaque formation in blood vessels, brain, and more.
Oxidative stress when uncontrolled damages cell membranes, DNA control switches, regulatory proteins and enzymes, which promote a chain reaction of tissue damage and chronic degenerative disease.
Modifiable Lifestyle Risk Factors for Chronic Disease
Western diets high in refined grains, sugars and meats are associated with proclivity towards poor glycemic control, insulin resistance and promotes systemic inflammatory responses. Distorted gut microbiome with reduced ecological biodiversity, pathogens and disruption in gut integrity are common threads to many chronic inflammatory diseases.
According to the U.S. Center for Disease Control and Prevention (CDC), out of the major chronic diseases, almost 80% of heart disease and stroke; 80% of type 2 diabetes; and, 40% of cancer can be prevented by controlling the three major risk factors – poor diet, inactivity, and smoking.
The structural framework for the prevention and management of chronic diseases involves recognizing lifespan and settings such as worksites, schools, communities, health systems and strategies targeted to specific stages of life (i.e., infants, children, adolescents, adults and older adults). The underlying risk factors for chronic degenerative disease include tobacco, nutrition, physical activity, alcohol and ultimately how they impact upon the individual’s genome. Finally the last leg of the three-legged stool, are the priority conditions to earmark for prevention and mitigation of chronic diseases; heart disease, stroke cancer, diabetes, obesity, arthritis, and oral health.
Role of Nutrition in Chronic Illness-Inflammatory Bowel Disease
The model we are using to discuss a strategy of nutritional modification to promote optimal outcomes is inflammatory bowel disease (IBD). There are 3 or more forms of IBD; Crohn’s Disease (CD), ulcerative colitis (UC), indeterminate colitis, and more. IBD involves a chronic intestinal inflammation causing tissue injury which promotes a vicious cycle of disease. In IBD, gut repair is impaired and there is increased oxidative stress in the gut and systemically. The uncontrolled inflammation can lead to a number of devastating consequences in CD and a higher risk of cancer in both CD and UC.
Dietary Factors and Risks of IBD.
There is emerging evidence that IBD was once a rare finding in Asia and India but its prevalence is rapidly on the rise in these regions due to Westernization of diet, lifestyle and possibly shifts in environmental exposures, sanitation, antibiotics use and more.
There is abundant epidemiological data demonstrating a link between the consumption of particular macronutrients and the risk of developing IBD. High dietary intakes of fats, red meats, refined grains and sugars have been associated with an increased risk of developing IBD. High dietary intakes of fiber and fruits were associated with decreased risk of CD, while high dietary intake of vegetables have been associated with decreased risk of UC.
In animal models of IBD there are a number of disturbing studies that link foods commonly consumed in the Western diet with a heightened risk of developing IBD.
Animal fat, milk fat, iron and emulsifiers promote disease flares in rodent models of IBD. High fat-sugar diet leads to intestinal dysbiosis, autoimmune enterocolitis, and leaky gut in an animal model for UC. A high-fat diet promotes more severe ileitis, gut dysbiosis, and autoimmunity in an animal model of CD.
Maltodextrin promotes inflammation by enhancing enteropathogenic bacteria adhesion and pathogenic biofilms which result in gut dysbiosis and inflammation. Iron and red meat promotes IBD in animal models but the disease response is mitigated by resistant starches-which promote the growth of probiotic flora.
There are a number of nutritional modalities, which have been shown to circumvent and or mitigate the course of IBD. Omega-3 fatty acids can help the immune cells cool off from their flame throwing release of proinflammatory and mediators and noxious biochemical. The evidence shows that omega-3 fatty acids can be helpful in preventing replace of CD noting that there lies variability in the outcomes data in one large study (negative) compared to smaller studies with 3 meta-analyses showing overall benefit. Omega-3-fatty acids have been shown in 3 studies to help induce remission for patients with active UC.
Curcumin is a polyphenolic compound derived from the medicinal spice curry. There are 2 well-designed randomized placebo-controlled trials of curcumin or placebo with mesalamine medications showing benefit for the induction and for the maintenance of remission of UC. Prebiotic and probiotic supplementations and medical foods have ample evidence to show benefit for mainly UC though questions about dosing and optimal species selection (probiotics) continue to allude practitioners and patients alike.
The concept of medical foods which contains a nutrient admixture that imparts a health benefit are emerging in use by the medical community. There are 2 studies using a unique formulation of prebiotics, antioxidants, omega-3 fatty acids that is nutritionally balanced and has been shown to help wean UC patients off corticosteroids and maintain remission of CD.
Immune modulating nutritionals include glutamine (equivocal data), butyric acid enemas for UC refractory to medical therapy (very good evidenced) and a new product on the marketplace Enteragam® which is concentrated purified bovine immunglobulins in a powder form for oral consumption which has several scientific abstracts, animal data, and chart reviews suggesting efficacy in IBD and the diarrhea-predominant irritable bowel syndrome (IBS-D). The mechanisms of action of this novel product (previously known as IgG2000 by Xymogen) involves gut barrier repair, immunoregulation, attenuation of inflammatory mediators and more.
Chronic diseases impart a major economic burden, afflict more than 125 M Americans and are on the rise with a projected 171M in 2030. Chronic inflammation mediates a number of pathophysiological consequences that result in tissue injury, DNA damage and impairments in glucose balance and energy metabolism.
The gut microbiome has a major controlling influence over immunity, immunoregulation, inflammation, epigenetic regulation and the development of chronic diseases. Distortions in the gut ecosystem results in disruptions of the communities of constitutive gut microbes and reduces its biodiversity resulting in barrier disruption and chronic disease development.
Finally, nutrition can modify the development and course of chronic diseases by improving the gut terrain, epigenetic regulation and combat inflammation-related chronic diseases.
Dr. Mullin, what possible role does gluten play in chronic disease?
ANS. Clearly in Celiac disease, gluten induces an autoimmune response that the vast majority improve upon dietary cessation of gluten foods and products. However, there is work by Dr. Alessio Fasano at Harvard showing how gluten itself can disable tight junction proteins that regulate intestinal epithelial cell function and cause barrier defects permitting antigen access to the circulation which may become triggers for autoimmunity.
Dr. Mullin, I have a question about how do we select probiotics for patients? Another attendee pooped up before I could respond and then asked-also Dr. Mullin this is related to his question- should we be buying these commercial stool kits to test our microbiome such as UBiome and have that guide our probiotic selections?
ANS. How intriguing. I believe probiotics have quite a bit of variation in terms of labeling which is a concern that consumers cannot trust manufacturers to adhere to Current Good Manufacturing Practice guidelines by the FDA. I think probiotics adhere to the 80/20 rule-that if you consume viable probiotics in mixed species formulation that it may not match your requirements but has enough of the right gut microbiomes to produce a positive effect. Ultimately we need PROVEN technology to guide our selections. There are many technology companies who are marketing stool testing of the gut microbiome but do not have valid applications at this time. A healthcare practitioner who is well-verse in the gut microbiome can best interpret these result for pertinent application-otherwise it’s not ready for prime-time for the public.
To Your Good Health,
Gerard E. Mullin