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NTR 340 TEST 2
ntr 340 test 2
42
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Undergraduate 3
10/19/2009
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Term
What is EBP, and what are the basic approach principles?
 Definition
 integrates individual clinical expertise with the best available external clinical evidence from systematic research
 prioritizes quantifiable data and quantitative research
 practitioners do not use peer discussions, experience, intuition as the only basis in practice
 practitioners do use results from clinical trials to guide decisions, actions
 should minimize faulty diagnosis, prolonged wrong therapies, and overall optimize health care process
Term
Approach principals:
 Definition
EBM guides, does not dictate, practice
 Practitioner must FORMULATE the question
 Practitioner must SEARCH the research literature
 Practitioner must critically EVALUATE the research literature
 Information is then APPLIED to the individual patient/client
Term
What is the best format for formulating the question?
 Definition
 PICO format
 P = Patient or problem of interest
 I = Intervention of interest, including treatment, risk factor, etc
 C = Comparison with alternative treatment, placebo, etc
 O = Outcome of interest (including time period if applicable)
Term
When searching for answers to various types of questions, which primary studies are most appropriate?
 Definition

Diagnosis Cross sectional study; sensitivity and specificity, positive and negative predictive value

Treatment Clinical trials, randomization, blinding

Prognosis Cohort study; follow-up studies, incidence/prevalence

Etiology Cohort study; case-control
Term
What are examples of patient/client outcomes?
 Definition
 Clinical assessment factors - biochemical parameters, anthropometry, clinical signs/symptoms
 Behavioral assessment factors - changes in food selection, preparation, PA -- may change clinical outcome
 Expected outcomes - improvements in abnormal lab values, BP, weight
Term
Why is secondary research performed? What are the advantages of utilizing systematic reviews?
 Definition
 Secondary data or studies
 Data not directly collected
 Cheaper and more quickly available
 Collect, analyze present findings from multiple studies
 Systematic review - provides overview of primary studies that used explicit, reproducible methods
 Addresses single, well defined clinical question
 Reduces literature for clinician
 Looks at consistency across studies, widens generalizability
 Meta-analysis - combines results of all available published studies that addressed the same hypothesis similarly to summarize quantitatively
Term
Why is the Cochrane Collaboration/Library considered to be a reliable and credible site for reviews? (read the article in Handouts)
 Definition
 Rely on grants and donations; do not accept "conflicted funding"
 Structured reviews using specific criteria to minimize bias; some using meta-analysis
 Continuously updated
 Review abstracts and plain language summaries are free, full text of review is for subscribers
Term
Name two websites you can use to find pre-evaluated research to answer your clinical questions.
 Definition
 National Guideline Clearinghouse
 www.guideline.gov
 Trip Database (Turning Research into Practice)
 www.tripdatabase.com
 PubMed [Set limits as noted]
 http://www.asu.edu/lib/resources/db/pmednlm.htm
 Clinical trials, meta-analyses, review articles, practice guidelines
 Ovid MEDLINE
 Search for ‘EBM reviews’
Term
What are limitations of or controversies surrounding EBP.
 Definition
 Not always agreement on "the evidence"; what constitutes quality research, how to best apply research evidence, and how to define effectiveness
 EBM promotes the randomized controlled trial (RCT) as superior to other study designs
 Meta-analyses are placed at the top of the hierarchy despite theoretical problems with pooling studies and empirical evidence that they may be misleading; interpretation is more problematic than usually is appreciated
Term
 Not always agreement on "the evidence"; what constitutes quality research, how to best apply research evidence, and how to define effectiveness
 EBM promotes the randomized controlled trial (RCT) as superior to other study designs
 Meta-analyses are placed at the top of the hierarchy despite theoretical problems with pooling studies and empirical evidence that they may be misleading; interpretation is more problematic than usually is appreciated
 Definition
 Second phase of mechanical, second phase of chemical digestion
 Gastric acid begins process of protein digestion
 Gastric protease (pepsin) digests very small amount of dietary protein
 Produced by gastric cells, converted from pepsinogen by HCl
 Gastric lipase digests very small amount of dietary fat
 Small intestine is MAJOR SITE of digestion
 MAJORITY of protein, fat, and carbohydrate digestion occurs here
 Small intestine produces protease and disaccharidase enzymes
 Duodenum receives enzymes from the pancreas; also bile and bicarbonate
 Pancreatic amylase - major role in finishing starch digestion
 Pancreatic protease - major role in finishing protein digestion
 Pancreatic lipase - major role in finishing fat digestion (with bile)
 VITAMINS
 Absorbed in their elemental form
 If they were digested, their chemical structures would be destroyed
 Food/supplement forms of vitamins and minerals are almost always in a chemical complex and must be digested prior to absorption
 E.g., lipid-bound fat soluble vitamins, amino acid bound minerals
Term
What does the enteric nervous system regulate(2), and what is it sensitive to( 2) in the process of digestion?
 Definition
 Nerve infrastructure regulates motility, secretions
 Intrinsic system - 2-nerve layer in gut wall; receptors sensitive to chyme comp, lumen distention
 External system - fibers running from CNS to ANS
Term
What is the effect of fear, anger, or stress on digestion?
 Definition
 Sympathetic nerve fibers
 Activated by fear, anger & stress
 Slow contents by inhibiting GI smooth muscle contraction & inhibiting secretions
Term
Know the name and a major function of each of the 6 major gut hormones
 Definition
 Gastrin - stimulates HCl, gastric motility, increases sphincter tone
 Secretin - stimulates output of pancreatic juice (contents?)
 Cholecystokinin [CCK] - stimulates pancreatic enzyme release, contraction of gall bladder
 Gastric inhibitory peptide (AKA glucose-dependent insulinotropic polypeptide) [GIP] - decrease gastric emptying, stimulates insulin release
 Motilin - stimulates gastric motility, emptying
 Somatostatin - decreases motility, regulates other hormones
Term
For Orlistat and Olestra; OTC starch blockers, Acarbose: who is it for, what is it supposed to do, what is the mechanism of effect, what is the risk if any, and has the product been proven to work in humans when used as directed??
 Definition
 Weight-loss medication designed to block fat digestion
 Works best with fat intake of 20-30% of kcal/meal, increasing fecal fat loss to ~30%
 If fat intake is >30%, GI distress is high
 If client is already on low fat diet, no effect, no weight loss
 Exerts activity in stomach and SI lumen by forming bond with active site of lipases and inhibits them (reversible)
 Inactivated enzymes thus unavailable to hydrolyze TGL into absorbable free fatty acids and monoglycerides
 Not absorbed; side effects related to blockade; anal oil discharge
 Olestra /Olean
 FDA approved fake fat sold as Olean
 Used by P&G in WOW chips, Pringles
 Not digested, so fat compound not absorbed, no calories
 Risks:
 GI distress: diarrhea, anal leakage of fatty matter
 Malabsorption of lipid soluble components including fat soluble vitamins and phytochemicals
 Acarbose
 Advantages:
 Brings down blood sugar and glycohemoglobin levels
 No hypoglycemia if this drug is used as only diabetic medication
 Most people will find it easier to lose weight
 Disadvantages:
 Most common side effects with starch blockers are: upset stomach, gas, or diarrhea; reportedly go away as you adjust
 Delays but does not SIGNIFICANTLY reduce digestion of dietary complex carbohydrates
 High doses cause abnormal liver enzymes
Term
What are the FACTS that refute the claims of raw foodism?
 Definition
 Enzymes required for food digestion have UNIQUE functions and are NOT the same enzymes as those used for other metabolic functions, nor are there a limited number produced
 “Metabolic enzymes” do not/cannot be used for food digestion
 Intake of “food enzymes” does not impact metabolic enzyme production or use
Term
What are benefits of cooking plant foods?
 Definition
 Heating, processing, cooking typically makes it EASIER for digestive enzymes to act, enhancing the digestive process Studies reflect compromised body mass and reproductive ability among individuals who follow a predominantly raw vegetarian diet
 Cooking is imperative for efficient extraction of energy from plant foods, even when those foods have been extensively processed by non-thermal methods
 Cooking contributes benefits that are not readily achieved with non-thermal processing, including gelatinization of starch, denaturation of proteins, killing of foodborne pathogens
 Cooking increases digestibility, cost of digestion, basal metabolism
 Few studies have directly compared raw and cooked meat with respect to energy, and results are contradictory
Term
What are risks of a raw food diet?
 Definition
 Participants had low cholesterol and triglycerides; they also had a vitamin B12 deficiency, leading to anemia and neurological impairment.
 Long-term raw foodists showed that they had healthy levels of vitamin A and dietary carotenoids, but lower than average plasma lycopene levels.
 Another study showed that low bone mass in the lumbar spine and hip may be another risk for raw foodists, who tend to be slim.
 Another study showed that a raw food diet can interrupt the menstrual cycle, because of drastic weight loss.
Term
What are the 3 main methods of nutrient absorption?
 Definition
Passive, Facilitated, Active
Term
What are the 3 main factors affecting absorption. What are the sites of nutrient absorption (what is absorbed where?)
 Definition
1. Efficiency of digestion
2. Health/function of GI tract, including length
3. Carrier availability
• Stomach: alcohol, fluoride
• Duodenum: Ca, Mg, Fe, Zn
• Jejunum: most fats, CHO, AA, B-vitamins
• Ileum: vitamin B-12, bile salts
• Colon: SCFA, water, electrolytes
Term
What factors does bioavailability of supplements depend on?
 Definition
 Bioavailability depends on:
 Disintegration time
 Dissolution %
 Types of excipients
 Nutrient forms
 Presence of co-factors or inhibitors
 Interactions with drugs
 Time of day taken
 Area in body where disintegration occurs
 Level of absorption at cellular level
 Need
Term
What should supplements have if they can be destroyed by stomach acid? Which mineral forms are the most bioavailable?
 Definition
 Enteric coating – disintegrates in SI
 For supplements that are destroyed in stomach
 Picolinates
 Gluconates
 Lactates
 Succinates
 Citrates
 Orotates
 Nicotinates
 Carbonates (usually classified as inorganic but function more like organic)
Term
Define controlled inflammation.
 Definition
Immune system perceives and responds to bacterial threats in measured way - mucosal adaptive immune system mediates defense and accommodation
Term
What is the role of gut microbiota in development of immunity, and how is the epithelial barrier protected and yet certain microbes tolerated (tight junctions, dendritic cells, T and B cells, IgA, GALT, mucus layers)?
 Definition
 Create barrier against invading microorganisms
 Competitive exclusion or colonization resistance
 Some have microbicidal properties; e.g. various strains can inhibit growth of H. pylori
 Synthesize proteins, acids [e.g. lactic acid] harmful to pathogens
 Stimulate/modulate gut immunity by adhering to intestinal mucosa
 Influences imprinting, maturation, and maintenance of mucosal immune system
 Stimulate sIgA, anti-inflammatory cytokine secretion, T-cell differentiation
Term
Define commensalism.
 Definition
 Intricate symbiotic relationship between eukaryotes and prokaryotes has evolved - commensalism
 Microbe gets stable nutrient supply/environment
 Host gains metabolic/digestive capabilities and competitive exclusion of less benign microbes
Term
When is the gut colonized by bacteria?
 Definition
 Gut microbes vary in types (bacteria, fungi, viruses), ratios throughout life
 Gut is sterile at birth; colonization is more rapid after vaginal birth vs C-section
 Breast fed infants have more beneficial profile of gut microbes vs. formula fed infants [pro- and prebiotics added to infant formula in Europe]
 By age 2 yr, child has gut microbe profile similar to an adult
Term
What regions of the gut have the greatest concentrations?
 Definition
 Esophagus none
 Stomach 104 cells/g
 Duodenum: 103
 Proximal ileum and jejunum 102-3
 Distal ileum 107-8 - dominant site of mucosal adaptive immunity which mediates inflammation and tolerance
 Peyer's patches (GALT) 'educate' T-cell pops
 Ascending colon (1011 cells/g) - account for 35-50% of colon contents by weight!
Term
How does the brain influence gut microbiota, and what is the main route of communication to the brain from the gut?
 Definition
 Bidirectional brain-gut interactions
 Brain influences enteric microbiota indirectly (changes in GI motility, secretions, permeability) or directly (signaling molecules released into gut lumen from cells in lamina propria)
 Vagus nerve provides direct pathway for communication
 Disruption of this communication involved in pathophysiology of bowel disorders
Term
What are some roles of the gut microbiota either directly or via production of short chain fats? What specific short chain fats are produced, and what are their distinctive roles?
 Definition
 Metabolism of plant compounds and drugs
 Inactivate potential carcinogens
 Activate certain drugs, herbs, phytochemicals via beta-glycosidases
 Lower levels of brain-toxic compounds
 Detoxify toxins, control yeasts which contain many antigens in fungal phase
 Enhance gut motility and function
 Modulate expression of genes that regulate nutrient absorption, mucosal barrier enhancement
 Influences production and composition of mucin, preservation of normal epithelial cell structure/function, determinant of gut motility
 Antioxidant protection of cellular lipids
 37% reduction in F-isoprostanes (OS marker)
 L. plantarum reduced blood levels of IL-6 by 42%
 Influence gut nervous system
 Modulate expression of genes that regulate synaptic neurotransmission
 Synthesize Factor-S, sleep-inducing substance derived from bacterial cell walls
 Digestion, absorption, synthesis of nutrients
 Synthesis of vits Bs, K; consume certain vits
 Metabolize oligosaccharides, fiber to produce short-chain fatty acids
Term
Define dysbiosis, SIBO. What is the impact of antibiotics on the microbiota?
 Definition
 Ecological disorder of bacterial community in gut
 Overgrowth of existing pathogenic microorganisms; decreased colonization resistance
 Decreased production of SCFAs, so impaired absorptive, metabolic, immune functions of gut
 Decreased therapeutic effect of some herbs, phytochemicals
 Often associated with pathogenesis of bowel disorders
 Gut microbial profile influenced by antibiotics (most common), stress, diet, altered peristalsis, radiation
Impact of antibiotics on microbiota
 Spectrum of activity
 Most affected by both gram+ and gram- agents
 Pharmacokinetics
 Site of absorption, excreted in bile, saliva, mucosa
 Generally oral antimicrobials are well absorbed in SI
 Dosage, length of administration
 The higher and longer, the greater effect; health status, multiple courses
 E.g. One antibiotic course can significantly lower serum enterolactone for up to 16 mos (protective phytoestrogen converted by bacterial enzymes from plant lignans)
Term
What are the effects of stress and why?
 Definition
 Increased activation of SNS, increased catecholamines, particularly NE (abundant gut innervation)
 → decreased production of IgA, greater pathogenic adherence to mucosa, particularly gram negative such as E. coli, greater shedding of beneficial bacteria
 Studies show psychological stress alters bacterial concentrations in body excretions
 Stress can increase production of polyamines in gut which are toxic
 Stress-induced gut changes (even short-term) lead to extended adverse milieu for Lactobacilli
 Reduced release of gastric acid, altered motility, increased bicarb production, reduced mucin and acidic mucopolysaccharides on mucosal surface
 Stress-derived mechanisms which alter bacterial composition of tract:
 Changes in epithelial cell function, mucus secretion, changes in GI motility, release of NE into gut may stimulate growth of specific pathogenic strains
 Stress during early life from maternal separation produced changes in rat microbiota associated with increased stress response, immune response, intestinal permeability, and shift in bacterial composition
 Stress during neonatal period results in intestinal barrier dysfunction and growth alterations later in life;
 Pre- and postbiotics can reverse the negative imprinting of neonatal stress on gut function
Term
What are the effects of excess total protein and animal protein intake, sulfur compounds, and high sugar intake on the gut environment?
 Definition
 >~100 g/d protein - as much as 12 g/d can escape digestion and reach colon
 Also extra enzymes, mucins, glycoproteins, epithelial cells
Impact of diet on microbiota - high animal protein intake
 Increases activity of certain bacterial enzymes
 Leads to increased toxic metabolites from excess polyamines and conversion of dietary chemicals and xenobiotics being circulated
 Impact of diet on microbiota - sulfur compounds
 Sources: sulfates in additives and preservatives, dried fruits, dehydrated vegs, shellfish, packaged fruit juices, baked goods, white bread, alcohol
 Natural foods with major sulfur AAs increase colonic production of sulfides - dairy, eggs, meat, cruciferous vegs
 Impact of diet on microbiota - high sugar intake
 Increases fecal concentrations of total and secondary bile acids as bile output increases
 Changes composition of population as bile acid-utilizing bacteria increase
 Increases quick fermentation in ascending colon
 Slows bowel transit time - increased exposure to potentially toxic bowel contents
 Insufficient carbohydrate? increased fermentation of mucin layer, reduced defense, inflammation?
Term
What is the hygiene hypothesis?
 Definition
 Inadequate exposure to microbes and their products due to modern hygiene standards may be detrimental
 Results in deficiencies in normal microbiota especially in early life during immune system development
 Strachan, 1986 - increasing rates of allergic disorders positively associated with increased household cleanliness and SES
 Bach, 2002 - declines in endemic infection rates correlated within same pop with increases in autoimmune diseases
 Developing countries have consistently lower incidences of immune/inflammatory conditions; same phenomenon observed in rural parts of developed countries
Term
Define ulcerative colitis and Crohn’s disease.
 Definition
Ulcerative colitis is restricted to the colon and anus. Inflammation affects the inner mucosal lining.

Crohn's disease can affect any part of the GI tract from the esophagus to the anus, but the majority occur in the ileum. Inflammation affects the whole intestinal wall.
Term
What are the biological and neurobiological factors involved in inflammatory bowel disease. What is the role of polyunsaturated (omegas) fatty acid intake balance and metabolism?
 Definition
 ~1 M people in U.S.
 Chronic inflammation of GI tract in genetically susceptible individuals, typically ages 15-30
 Incurable, with high morbidity
 Symptoms include GI tract disturbances, ulceration, fistulas, bowel obstruction; weight loss, fever, anemia, delayed growth in children, depression
 Treatment - elemental, elimination diets to antibiotics, anti-inflammatories, immunosuppressive drugs
 Human n-3 trials lack consistent benefit for IBD so far, but some report improved gut histology, decreased progression, use of meds, relapse
Term
Define irritable bowel syndrome. What are the biological and neurobiological factors involved in this disease?
 Definition
 Disorder that interferes with normal colon function
 Affects 20% of population; 10X more common in women
 Symptoms include abdominal cramps, bloating; diarrhea or constipation (normal motility disruption)
 Associated with stress, large meals, wheat, fructose, sugar alcohols, lactose, coffee, gas-producing foods, fat
 Treatment includes stress management, avoidance of offending foods, anti-depressants
 Neurobiological factors of IBS
 Disorder of gut-brain axis; historically viewed as psychosomatic disorder
 Evidence emerging of dysbiosis in IBS patients
 Several studies observed reduction in Lactobacilli (diarrhea-predominant) or increase in Veillonella species
 Strongest risk factors: acute bacterial gastroenteritis, antibiotic usage in children or in context of postinfective IBS; also enteric infection, stress
 Biological factor of IBS
 Evidence of low-grade inflammation without tissue damage in animal studies; confirmed by mucosal biopsies in subset of IBS patients
 Incremental increase in gut's controlled inflammation that is subclinical but sufficient to alter neuromuscular function and produce GI symptoms
 Gastroenteritis and low-grade inflammation are underlying mechanisms, particularly in patients with demonstrable intestinal dysbiosis
Term
Define probiotics, and give food examples. What few conditions are they clinically efficacious for at this point?
 Definition
 Lower risk of and/or lessen severity of diarrhea [children and adults] and gut-associated infections
 Optimize establishment of gut microbes in newborns
 Reduce symptoms of food allergies in children and infants
 Lowers risk of necrotizing enterocolitis in VLBW preemies
 Lowers risk of respiratory infections
 Adjunct therapy for Crohn’s disease, IBD, lactose intolerance
 Lower risk of illness after antibiotic use - recolonize gut bacteria; broad-spectrum antibiotics can result in Clostridium difficile colitis, diarrhea
Term
What characteristics must bacterial species have to be considered good probiotic candidates? What should labels specify?
 Definition
 Supplement qualitatively and quantitatively optimized bacteria
 Microorganisms in product are specifically identified, e.g. Lactobacillus bulgaricus
 Bacteria are stable and viable within product as stored and used, i.e. present as LIVE cells, in high amounts [e.g. 1010 cfu colony forming units per serving]
 Bacteria survive gastric environment and exposure to bile
 Bacteria exert effect in intestinal tract by adhering to epithelial cells and/or mucus secretions and proliferate
 ID specific strain
 Define proposed function in vitro, in animals
 Assess safety in vitro, in animals, in humans
 Appropriate labeling of product
 Name(s) of probiotic(s) in the food
 Minimum # of viable organisms
 Shelf life, dated
 Definition of proper storage conditions
 Human trials, adequate size, etc.
Term
Why would an S. boulardi yeast supplement be considered a good probiotic candidate and when would it be a wise choice?
 Definition
 Good probiotic candidates; commensal bacteria may act as reservoirs of antibiotic resistance genes, transfer resistance genes to pathogenic bacteria
 4 large scale placebo-controlled clinical studies showing significant efficacy for preventing antibiotic associated diarrhea (Czerucka, Pieche, Rampal, 2007)
 Increased mucosal disaccharidase activity in rats and human volunteers (Elmer et al, 1996)
 Used in Europe since 1960s; achieve steady-state colon concentrations within 3 d of repeated administration; cleared 2-5 d after discontinuation
Term
Define prebiotics, synbiotics, and postbiotics. For each if applicable, what are food sources (inulin, oligofructose?, etc) and benefits. When would you use each?
 Definition
 Prebiotics
 Non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth/activity of one or more colonic bacteria
 Other components of dietary fiber (including pectin & hemicellulose)
 Various legumes (black beans, kidney beans, chickpeas, lentils, white beans)
 Whole grains, barley, oatmeal, flax
 Green leafy vegetables (kale, chard, collards, mustard greens, spinach, dandelion greens)
 Fruits (bananas, melons)
 Synbiotics
 Prebiotic substrates + probiotics - products that contain both

 Postbiotics
 Isolated bacterial components, products such as butyrate and other SCFAs that delivered via dietary supplementation
 'Non-viable' - avoids risk of sepsis in patient with compromised intestinal barrier function
 Similar to concept of vaccination - stimulates adaptive immune system
Term
What are other requirements for gut health?
 Definition
 Adequate calcium and vitamin D
 Adequate copper, iron, selenium, zinc which modulate immune system in gut
 Decreasing ratio of n-6 to n-3 to modulate eicosanoid production
 Adequate fluid
 Appropriate physical activity
 Appropriate stress management
 Appropriate therapies: antibiotics, elemental nutrition (SIBO, Crohn's)
Term
What is the role of fiber (which type?) in gut health?
 Definition
 Improved laxation (I)
 Provides substrate for fermentation (S)
 Blunts elevation in blood glucose after meal (S), improves insulin profile
 Lowers serum cholesterol (S)
 Increases satiety (I, S)
 May see terms “fermentable” and “non-fermentable” fibers vs. soluble and insoluble
Term
What are examples of the three types of non-pharmaceutical health-promoting interventions?
 Definition
 Nutrition is key to prevention/management of gut health
 Non-pharmaceutical interventions have fewer negative side effects, produce beneficial side effect
 Primary prevention
 E.g. Safe food handling, milk/juice pasteurization, etc.
 Secondary prevention - early detection/treatment to minimize progression
 E.g. Early diagnosis of gastric ulcer and appropriate treatment
 Tertiary prevention - advanced aggressive treatment to reduce complications
 E.g. Surgical removal of colon cancer to prevent further spread
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