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Day06-Guide01 - Nutritional Deficiencies Clinical Symptoms
1. Excess of which nutrients are associated with Kayser-Fleischer rings?
Copper
2. Deficiency or suboptimal levels of which nutrients are associated with red, swollen, inter-dental gingival hypertrophy?
Vit C, Folate, B-12
3. Deficiency or suboptimal levels of which nutrients are associated with cheilosis?
Riboflavin, niacin
4. Deficiency or suboptimal levels of which nutrients are associated with glossitis?
Niacin, riboflavin, b12, folate, b6, iron.
5. Deficiency or suboptimal levels of which nutrient is associated with fissured tongue?
Niacin
6. Deficiency or suboptimal levels of which nutrients are associated with hypogeusia?
a. Zinc, Vit A
7. Deficiency or suboptimal levels of which nutrient is associated with xerosis of the eye?
a. Vit A
8. Deficiency or suboptimal levels of which nutrients are associated with dermatitis?
a. Essential fatty acids, zinc, niacin, riboflavin
9. Deficiency or suboptimal levels of which nutrients are associated with delayed wound healing?
a. Vit C, Zinc, Protein, Calories, possibly linoleic acid,
10. Deficiency or suboptimal levels of which nutrients are associated with ecchymosis (bruising) with minor trauma?
a. Vit K, Vit C, Protein-energy malnutrition
11. Deficiency or suboptimal levels of which nutrients are associated with pellagrous dermatitis?
Niacin, Tryptophan
12. Deficiency or suboptimal levels of which nutrients are associated with follicular hyperkeratosis? (picture of back of an arm)
Vit A, Essential fatty acids, zinc.
13. Deficiency or suboptimal levels of which nutrients are associated with dry, scaling skin? (picture of heels)
Vit A, Essential fatty acids, zinc.
14. Deficiency or suboptimal levels of which nutrients are associated with koilonychias (spoon nail)?
Iron
15. Deficiency or suboptimal levels of which nutrients are associated with white spots on the nail?
Zinc, Selenium
16. Deficiency or suboptimal levels of which nutrients are associated with dull, thin, sparse hair?
Protein, Iron, Zinc, Essential Fatty Acids
17. Deficiency or suboptimal levels of which nutrients are associated with bone pain/tenderness?
Vit C, Vit D
18. Deficiency or suboptimal levels of which nutrient is associated with muscle tenderness or pain in bilateral calf and thigh?
Thiamin
19. Deficiency or suboptimal levels of which nutrients are associated with motor weakness in lower extremities?
Thiamin, E, D
20. Deficiency of which nutrients are associated with Rickets?
Vit D, Calcium
21. Deficiency of which nutrients are associated with confabulation (attempt to fill in memory gaps by fabricating information or details)?
Thiamin
22. Deficiency or suboptimal levels of which nutrients are associated with dementia?
Thiamin, Vit B12
23. Deficiency or suboptimal levels of which nutrients are associated with depression?
Thiamin, Vit B12, Potassium, Essential Fatty Acids.
24. Deficiency or suboptimal levels of which nutrients are associated with peripheral neuropathies?
B1 B6 B12 (thiamin, pyridoxine, cobalamin
Day06-Guide02 - Adv Nut. Human Metab. - Intestinal Bacteria (Microflora), Pre-and Probiotics, and Disease
1. What factors affect the composition of the microflora?
a. Substrate availability, pH, medications, diet.
2. What do intestinal bacteria use as substrates for their growth?
a. Unabsorbed food residues in the intestines
3. What is the anaerobic process of breakdown of carbohydrates and proteins by bacteria called?
a. Fermentation
4. What are the primary short chain fatty acids (SCFA) produced by bacterial carbohydrate fermentation in the large intestine?
a. Acetate, butyrate, propionate
5. What purpose do the SCFA’s serve?
a. Stimulate GI cell proliferation, lowers pH in lumen of colon, provide substrate for body cell growth b. Propionate and lactate are taken up in colon and used for liver cells
6. Which SCFA is the preferred energy source for colonic epithelial cells and may regulate gene expression?
a. Butyrate can be absorbed via a Na/H pump and used for gene expression
7. Which SCFA is absorbed and used by muscle cells and brain cells as an energy source?
a. Acetate used for muscle and brain cells
8. What is lactose intolerance? What are the symptoms? What is the official way to diagnose this condition?
a. The enzyme lactase is not produced sufficiently. Large amounts of H gas are produced, and this is the official way to diagnose the condition
9. What are prebiotics? How are they health promoting?
a. Food ingredients which are not digested by the host, and are designed to promote growth of one or more bacteria flora in the gut. The growth of good beneficial bacteria displaces the growth of pathogenic bacteria.
10. How are probiotics generally thought to exert their health promoting effects?
a. Food that contain specific strains of live bacteria. Yogurt or fermented milk are sources. Promote health by increasing IgA production, tighten mucosal barrer. Displace pathogenic bacteria. Acidify colon via fermentation products. Promote excretion of toxins. Enhance fecal bulk, increasing transit time, decreasing time to absorb toxins.
Day06-Guide03 - The Role Of The Gut Microbiota In Defining Human Health
.
How many distinct bacterial species live in the distal G.I. tract? How many total microorganisms live in the distal GI tract? (page 1)
1000 distinct. 1x10^14 total.
What is the estimated numerical relationship of microbial cells compared to host cells in mammals? (page 1)
microbes to human 10 to 1. Microbial to human genome 100 to 1.
How does the bacterial community composition differ in patients with diseases (e.g. obesity, periodontal disease) as compared to healthy subjects? (page 2)
dramatically altered; healthy subjects typically exhibiting distinct, diverse and temporally stable bacterial consortia at these sites when compared with patients displaying disease symptoms.
What major phyla in the human GI tract seem to be in an altered ratio in obese individuals? What is the ratio? How is this altered community structure related to obesity? What kind of dietary patterns seem to increase this ratio ?(page 2)
dramatic tenfold shift in the ratio of Firmicutes to Bacteroidetes (from 3:1 to 35:1) resulting in increased energy harvest from ingested food; unexpended excess energy is deposited as adipose tissue. High fat increase ration further.
Aberrant TH17 populations are associated with which chronic diseases? (page 3)
1. (IBD), 2. lupus, 3. MS , 4. psoriasis, and 5. RA, disorders that are believed to be linked to GI dysbiosis.
How does maternal exposure to microbes during pregnancy relate to postnatal development of allergic disease? How does it impact T-cell balance and Toll-like receptors? (page 3)
decrease allergic responses. Tregs increase and TLR’s as well (which interact with bacteria).
How does maternal prenatal exposure to antibiotics relate to risk for development of childhood asthma? (page 4).
Increase allergic response.
A diverse ecosystem of the human gut microbiome encodes for what essential functions that the human host is incapable of performing? (page 4)
vitamin production and metabolism of indigestible dietary polysaccharides
How does the immune system initially develop to discriminate between beneficial (“friend”) and harmful (“foe”) microbial species? (page 4)
primarily dependent on postnatal immune development, which is increasingly associated with appropriate microbial colonization of the GI tract.
By what age does the gut community of microbes begin to resemble that of an adult-like microbiome? (page 5)
12 months.
What is the hygiene hypothesis? How might this be related to GI colonization and allergic disease? (page 5)
The hygiene hypothesis, originally based on the observation that children with older siblings exhibit a reduced incidence of allergic disease, was postulated to be due to exposure to viral infections
What key factors impact gut microbiome composition in the early stages of infancy and have been associated with subsequent childhood asthma and allergy development? Infants born under what conditions exhibited the most beneficial gut microbiota? How was “beneficial” characterized? (page 5-6).
C-Section, formula, hospitalization, preterm and antibiotics. full-term infants born vaginally at home, who were exclusively breastfed were least atopic with gut high in Bifidobacteria and reduced abundances of E. coli and C. difficile.
How does breastmilk shape the developing GI microbiome over the first year of life? Which diseases are specifically mentioned as having a lower incidence in infants who have been breastfed? (page 6)
nutrition, IgA, growth of specific families like Bifidobacteria. neonatal diarrhea, necrotizing colitis, obesity and Type II diabete.
What intestinal morphologic changes occurred in mice supplemented daily with a strain of Bifidobacteria isolated from Chinese centenarians? (page 7)
increased villus height and crypt depth.
What is dysbiosis? Imbalance in what immune cells has been associated with dysbiosis? (page 7)
Disruption of the gut microbiome. populations of inflammation-mediating T-helper cells (Th1, Th2 and Th17) and anti-inflammatory Treg cells.
Overproduction of Th1 and Th17 associated cytokines has been linked to what diseases/disorders? Increase in Th2 cells and associated cytokines has been linked to what diseases/disorders? (page 7)
High Th1 in Chron’s Disease. Th17 in ulcerative colitis and CD and lupus, multiple sclerosis, psoriasis and rheumatoid arthritis. Th2 in asthma, allergic disorders and UC.
What general characteristic of the adult gut microbiome is associated with many diseases and disorders? (page 7)
overall reduction of bacterial diversity.
How does antibiotic administration impact the native microbial community? For how long? (page 9-10)
dramatically impacts the native microbial community, leading to an unintentional state of dysbiosis. 4 weeks.
In the treatment of chronic diseases by microbial manipulation of the host microbiome, by what mechanisms do administration of probiotics seem to work? (page 10)
probiotic therapy represents alteration of the gut microbiota by supplementation with live microorganisms that function to 1) inhibit pathogen adherence to the mucosa, 2) improve the intestinal epithelial and mucosal barrier function, 3) produce bacteriocins 4) increase IgA production and 5) downregulate proinflammatory cytokine secretion. In UC, defensins are down-regulated.
What are prebiotics? (page 10)
nondigestible food ingredients that improve host health by stimulating the growth or activity of colonic bacteria, have now been reclassified to include components that are resistant to gastric acidity, hydrolysis by host enzymes and absorption by the upper gastrointestine, ARE fermented by the gut microbiota, and stimulate growth of microbial species beneficial to the host's health.
What was the result of the clinical trial mentioned in the paper that used the probiotic preparation VSL#3 on patients with mild to moderately active ulcerative colitis? (page 11)
induced remission in significantly more patients than those treated with mesalazine (ASA).
Day07-Guide01 - IM, Rakel - Ch. 85 Maintaining Health and Aging Optimally
1. What are some “biomarkers” of aging?
a. Loss of strength b. Reduced flexibility c. Decreased cardiovascular endurance d. Increased body fat (and resultant loss of muscle mass – sarcopenia) e. Reduced resting energy expenditure f. Diminished kidney clearance g. Reduced cell-mediated immunity h. Higher hearing threshold i. Reduced vibratory sense j. Compromised near vision and dark accommodation k. Reduced acuity of taste and smell l. Altered hormone levels m. Increased autoantibodies
2. What are some theories and principles of aging common to most mammals?
a. Cell doubling – max of 90 doublings for most human cells over 120 years b. Telomere shortening c. Loss of Vo2 max (max O2 consumption) or O2-carrying capacity d. Caloric restriction – can extend lifespan e. Longevity genes – found in long lived individuals f. Morphic resonance – body’s form and structure resonates and adapts to environment g. Allostatic load – interaction of genetic with environmental and lifestyle factors
3. What is McEwen’s concept of allostatic load with regard to aging?
a. Each persons signature of aging is a result of interactions among genetic makeup, lifestyle, diet and environmental changes
4. How many years does the study that looked at Seventh Day Adventists suggest that optimal lifestyle behaviors can increase life expectancy?
a. 10 years
5. What do the results of longitudinal studies tell us about the rate of changes taking place with normal aging?
a. Normal aging appears to be a phenomenon of gradual rather than precipitous change
6. In general when does decline in physiologic function begin? How does it differ in persons leading optimal lifestyles as compared to those that are sedentary and overweight?
a. In general decline in normal physiologic function begins after 30 years. Nice Lifestyle -0.5%/yr but sedentary and overweight -3%/yr.
7. How does oxidative stress relate to aging and age-related disease?
a. Unrepaired damage (from mitochondrial level to organ level) due to free radicals accumulates with age. Some age-related disorders exacerbated by are Atherosclerosis, hypertension, diabetes, osteoarthritis, dementia, Parkinson’s. antioxidants means longer lifespans.
7. How is hyperglycemia associated with the aging process?
a. Excessive intake of refined carbohydrates and consequent sustained high fasting insulin levels can cause protein cross-linking and ultimately to blood vessel wall and connective tissue hardening. This is also known as the metabolic syndrome. Although signs and symptoms of metabolic syndrome occur with greater frequency with aging, they can be prevented with lifestyle modifications like increases in physical activity and reduction of stress.
9. According to the author, what is at least one reason for chronic inflammation and age associated diseases where inflammation plays an important role?
a. Chronic inflammation occurs with age primarily due to imbalance in the ratio of Omega-6 to Omega-3 fatty acids. Prehistoric diets used to take in 1:1 and now they are 45:1
10. How do altered methylation reactions relate to aging?
a. With age, deficiencies in B6, B12, and folate can alter in methylation reactions leading to lower amounts of beneficial compounds like S-adenosyl methionine (SAMe) and excesses of harmful ones like homocysteine.This can lead to coronary artery disease, cerebrovascular disease, DVT, DM type 2, rheumatoid arthritis, osteoporosis, dementia, depression ad other psych conditions.
11. What affect can the low concentrations of airborne particulate matter in air pollution have with regard to atherosclerotic lesions?
a. Long term exposure to low concentrations of airborne particulate matter in air pollution can alter vasomotor tone, induce vascular inflammation, and potentiate the development and progression of atherosclerotic lesions
12. What is the effect of prolonged stress and sustained elevations of cortisol on the neuronal connections?
a. Prolonged stress can cause chronic elevations in cortisol; prolonged exposure of brain to high levels impairs neuron-neuron connections, furthering cognitive decline, furthering the incidence of depression.
Day07-Guide02 - Adv Nut. Human Metab. - Osteoporosis and Diet pp. 461-465
1. On average, after what age range does bone resorption exceed bone formation?
30-35 yo
2. Using the front cover of the book as your reference, what is the adequate intake (AI) for calcium intake in men and women in the range of 19-50 years of age? What is the upper limit (UL)? Compared to the range 19-50 years of age, is the AI higher or lower during adolescence? During advanced age?
1 g/d for both, 2.5 g/d upper limit, Higher, Higher!
3. If calcium intake is less than adequate what hormone level rises to maintain serum calcium ion concentration?
PTH
4. By what mechanism does age related decline in kidney function magnify the age related decline in intestinal absorption of calcium?
Lower production of vitamin D in the kidney leads to less intestinal absorption, which vitamin D stimulates.
5. The intake of what vitamin along with the mineral calcium is necessary to ameliorate bone loss following menopause in females? What hormone level drops following menopause that accelerates bone loss?
Vitamin D, Estrogen
6. By what mechanism does calcitriol increase intestinal calcium absorption?
Promotes transcription in enterocytes of calbindin, which functions as a Ca binding protein. Calcitriol may also induce changes in the intestinal membranes that increase absorption.
7. What are the several conditions or mechanisms that often lead to poor vitamin D status in the elderly?
Marginal intake, poor sunlight exposure, decreased transformation into active form (calcitriol) within kidney
8. Are there studies to demonstrate that supplemental vitamin D and calcium reduce risk of hip fractures, or vertebral fractures
Yes
9. What is the effect of high sodium intake on the body’s calcium balance?
Detrimental (decreasing/negative) effect
10. Does adequate potassium intake alter salt-induced calcium excretion?
Yes, lowers calcium excretion
11. What is the mechanism underlying the theory that excess protein and other net acid producing foods (meat, fish, cheese, grains, and phosphoric acid containing soda) impair bone health?
Possible low grade acidosis that results may be offset by providing carbonate from bone after bicarbonate buffer system and renal excretion are overpowered. This corrects acidosis, but breaks down bone.
12. What is the evidence that adequate protein intake is necessary for bone health?
Generally, 1. increased bone mass, 2. reduced bone fractures, 3. shorter healing times. Mechanistically, 4. adequate protein intake > increased Ca gut absorption and 5. protein intake in natural food accompanies food that counteracts protein Ca kidney excretion.
13. Why is adequate vitamin C and K intake required for bone health?
Both are important for synthesis of various proteins found in bone, for example collagen is dependent on Vit C.
14. Is vitamin K intake correlated with incidence of hip fractures?
Yes, low vit K intake correlated with increased rate of hip fractures.
15. Is fluoride recommended or approved for prevention or treatment of osteoporosis?
No
16. What relationship exists between smoking and bone density or fracture risk?
Negative effects, low density
17. What relationship exists between chronic and excessive ingestion of alcohol?
Negative effects, bone damage
18. What relationship exists between caffeine ingestion and bone health?
Negative, increased urinary Ca excretion
19. What other trace minerals if deficient can cause poor bone health?
Boron and magnesium. Added copper, zinc, and manganese are effective in stopping post menopausal bone loss.
20. What effect does weight-bearing exercise on a regular basis have on bone?
Positive effect, increased bone density
Day07-Guide03 - Textbook of Functional Medicine (chapters 2 and 3)
1. What will be a major challenge for medicine in the 21st century according to the authors in the introduction portion of the chapter?
A major challenge “will be to move toward a thorough understanding of physiological mechanisms that underlie disease rather than simply labeling later-stage effects with the names of diseases.”(Pg. 5) In other words, trying to learn to catch a disease before its onset, and therefore treat the patient and restore health before there even is a chronic illness or disease.
2. In the Functional Medicine model for approaching complex chronic diseases, where is the focus placed during the assessment and treatment? How does it differ from a conventional approach?
1. Fxnal Medicine first address the patient’s core clinical imbalances, fundamental physiological processes, environmental inputs, and genetic predispositions, rather than heading straight for the 2. diagnosis as is done in Conventional. These treatments focus on restoring 3. health and 4. function, rather than simply controlling 5. signs and 6. symptoms. (Pg.6)
3. What environmental inputs affect genetic expression?
Many environmental factors that affect genetic expression are (or appear to be) a matter of choice (such as 1. diet and 2. exercise), but others are very difficult for the individual patient to alter or escape (3. air and 4. water quality, 5. toxic exposures) and others may be the result of unavoidable accidents (6. trauma, 7. exposure to harmful microorganisms in the food supply through travel). 8ish. Economic status can also be heavily influencing environmental input. (Pg.6-7)
4. Name the fundamental physiologic processes that ultimately define health or disease.
1. Communication, both outside and inside the cell; 2. bioenergetics, or the transformation of food, air, and water into energy; 3. replication, repair and maintenance of structural integrity, from the cellular to the whole body level; 4. elimination of waste; 5. protection and defense; and 6. transport and circulation (Pg.8)
5. What are the core clinical imbalances that develop as a result of the interaction of environmental inputs and genetic predisposition and alteration in fundamental physiologic processes?
1. Hormonal and neurotransmitter imbalances 2. Oxidation-reduction imbalances and mitochondropathy 3. Detoxification and biotransformational imbalances 4. Immune and inflammatory imbalances 5. Digestive, absorptive, and microbiological imbalances 6. Structural imbalances from cellular membrane function to the musculoskeletal system
7. Why are today’s healthcare providers not adequately trained to manage the increasing burden of complex, chronic illness?
1. the gap between emerging research in basic sciences and integration of new knowledge into clinical practice is often astonishingly large-particularly in the area of complex, chronic illness. (Pg. 15) 2. Also, there was a time when our healthcare system was becoming dependent on advances in acute care, yet other influences were superseding acute conditions as the greatest threats to American health, ie. stressful and sedentary lifestyles, industrial pollution, devitalized food, overconsumption of food, etc.
8. How is today’s general concept of prevention too limited?
1. Disease prevention has too often been conceptualized as immunization and early diagnosis, an approach that is far too limited. Effective prevention of chronic disease today requires understanding individual genetic vulnerabilities (20–30% of chronic disease risk) and the effect of lifestyle upon those individual variations (70–80% of the risk). Also physicians are untrained for nutrition interventions.
9. In discussing healthy aging, what would be the goal that is within our reach in the ideal case?
1. survive to an advanced age with their vigor and functional independence maintained, and 2. morbidity and disability will be compressed into a relatively short period before death occurs (Pg.19)
10. What are the most effective and least costly tools for lifelong disease prevention?
1. Diet, 2. exercise, 3. stress reduction, and 4. active lifestyles (Pg.19)
11. What percentage of the increase in prevalence of Type 2 Diabetes can be attributed to a changing environment?
100% of the increase in the U.S. during the latter half of the 20th century.
12. In reference to the genetics-environment interface, how can macro and micronutrients influence one’s phenotype?
Although the human genome contains only between 1. 30k genes, millions of variations of these genes, called 2. (SNPs), exist. These polymorphisms occur as variations in which the 3. least common allele is present in at least 1% or more of the population. Many of these SNPs lead to differences in the phenotype of an individual, and how these differences are expressed depends upon environmental factors. One major factor is the individual’s nutritional status. Both macro- and micronutrients can influence the 4. expression of genes, 5. the translation of the genetic message into active protein, and 6. that protein’s ultimate influence in controlling metabolic function.” (Pg.20)
13. What is nutrigenomics?
The interface between genomics and nutrition. Dr. Linus Pauling alerted physicians to the importance of nutrients in modulating physiological processes at the biomolecular level and ultimately giving rise to the phenotype of health or disease. (Pg.21)
14. What is the difference between upstream and downstream medicine?
In the last few decades, much medical research has focused primarily on discovering specific molecules that inhibit enzyme function downstream in a complex physiological process. Genomic and proteomic research has begun to demonstrate, however, that rather than blocking specific enzymes downstream in a complex biological system associated with a specific disease, it can be even more effective to develop new approaches that would selectively regulate the expression of various alarm molecules upstream in the metabolic process that are associated with the disease.
Day07-Guide04 - Adv Nut. Human Metab. - Nutrigenomics: The Foundation for Personalized Nutrition p. 29
1. How do genetics and genomics differ?
Genomics encompasses genetics (how genes are inherited) and applies it further to how variation in a gene changes the organisms function and adaption to its environment, and finally how environment adapts genes.
2. What is nutrigenomics?
Study of how bioactive food components affect gene expression and function.
3. What is pharmacogenomics?
Study of interaction between genes and drugs.
4. What can physicians now analyze to predict which drugs and dosage will be effective for a given patient?
Key drug metabolizing enzymes
5. Name some classic examples of highly penentrant single gene disorders that give rise to inborn errors of metabolism mentioned by the author.
AA metab like 1. PKU, 2. maple syrup urine disease. Carb metab like 3. galactosemia, 4. hereditary fructose intolerance. Lipid metab like 5. familial hypercholesteremia, 6. medium chain acyl-CoA dehydrogenase deficiency.
6. How do less penetrant, more common, more subtle gene variations (polymorphisms) compare to the gene disorders that are highly penetrant? Why are they the primary focus of nutritional genomics?
They do not directly cause disease, they alter the susceptibility to acquiring disease. They are common, they affect dietary recommendations for what foods are best for an individual, and practical interventions are possible.
7. Referring to the seminal paper published by Ames and colleagues in 2002, what did people who had one of the 50 enzyme variants need to compensate for the decreased function of the enzyme?
Increased folate intake to offset decreased recycling activity of Methylene-tetrahydrofolate reductase (MTHFR)
8. By which mechanisms is environmental information (such as bioactive nutrients) able to influence gene expression? Describe how transcriptional factors influence initiation of transcription.
Signals about nutritional sufficiency induce change in gene expression primarily through transcriptional regulation. They bind to response elements on a specific region of DNA that lead to conformational changes that permit (or inhibit) RNA polymerase attachment to promoter region to then transcribe gene.
9. Describe how ligands derived from food coordinate to affect genes involved in lipid metabolism and oxidation via the RXR and PPARgamma receptors.
In order for these transcription factors to activate and induce gene transcription they have to form a heterodimer and must each bind their respective ligands, which are vitamin A and PUFA (omega 3) respectively. Hence nutritional concentrations regulate genes.
10. What is the APOE gene? What are the three common gene variants? Which is the most common? People with which variant have the highest basal levels of various lipids? What kind of diet results in the greatest lipid lowering response in people with this variant?
Encodes a protein that facilitates interaction between triglyceride rich chylomicrons and intermediate density lipoproteins. E2, E3, and E4 are common gene variants, E3 most common, highest basal levels of lipids is E4, and for E4 people a low fat diet is most powerful.
11. People with which APOE variant have low serum cholesterol levels but high triglyceride levels? To what dietary interventions do they respond best?
E2, Oat bran and other soluble fibers, also fish oil supplementation and endurance exercise.
12. People with which APOE variant respond to fish oil supplementation with increases in total cholesterol and lower HDL (an effect counter to the desired one)?
E4
Day07-Guide05 - Adv Nut. Human Metab. - Nutrient Drug Interactions pp. 533-535
1. What is a nutrient-drug interaction?
Nutrient induced changes in drug metabolism or, drug induced changes in nutrient metabolism.
2. What cytochrome p450 enzyme does grapefruit down-regulate? What impact can this have on drugs that are substrates for this p450 enzyme when co-ingested with grapefruit juice?
Grapefruit down-regulates CYP3A4 in the intestine, which normally induces intestinal cell metabolism of many drugs. Lack of it will cause the drug to pass into blood not metabolized. This in turn causes higher plasma concentrations than desired.
3. What nutrient is affected by the use of Warfarin (Coumadin)? What is the mechanism?
Vitamin K. Warfarin normally works by inhibiting the conversion of K to the active form. This prolongs clotting time. Large amounts of K will overwhelm the drug, and produce unwanted effects. K is found in green leafy vegetables.
4. Which nutrients may have diminished absorption in the presence of drugs that raise gastric ph in the treatment of ulcers and gastroesophageal reflux disease (such as proton pump inhibitors and H2 blockers)?
B12 and iron (low IF).
5. Which nutrients may be poorly absorbed in the presence of bile acid sequestrants used in the treatment of high blood cholesterol levels?
A,D,E,K, the fat soluble vitamins and carotenoids. Also folate and Fe, Mg, Ca, Zn.
6. Which drug diminishes the conversion of pyridoxine (Vitamin B6) to its functional form in the liver? For what condition is this drug used? (this can cause permanent peripheral neuropathies)
Isoniazid (INH) used for tuberculosis.
7. Which vitamin’s metabolism is altered by anticonvulsants like phenobarbital and phenytoin and may lead to rickets and osteomalacia? What is the mechanism? What other vitamin is poorly absorbed in the presence of these drugs?
Vit D, leads to rickets and osteomalacia. The drugs diminish hepatic conversion of vit D to 25-OH cholecalciferol. Also blocks folate absorption.
8. What impact do loop diuretics have on minerals? (some of these deficiencies are primarily intracellular and may not show up on serum blood tests)
Promote excretion of sodium and water. But can increase reabsorption of K, Cl, Mg.
9. What nutrient may be affected by the use of NSAID anti-inflammatory agents like Ibuprofen? What is the mechanism?
Folic acid. Competitively inhibits the enzymatic synthesis of folic acid.
10. What nutrient may be affected by the use of HMG-CoA Reductase Inhibitors (Statins used to lower high blood cholesterol)? What is the mechanism? What are potential effects?
CoQ10 (ubiquinol). HMG-CoA is also necessary for synthesis of CoQ10. Can affect cellular energy production, regulation of blood pressure, antioxidant function, cardiac function, and muscular pain.
Day07-Guide06 - Adv Nut. Human Metab. - Genetics and Nutrition: The Possible Effect on Folate Needs and Risk of Chronic Disease, pp. 370-371
1. What is MTHFR?
Enzyme that catalyzes conversion of methylene THF to methyl THF allowing continued conversion of homocysteine to methionine.
2. What occurs if MTHFR activity is low?
Impaired methionine levels with resulting low levels of methyl groups available for methylation. Additionally, poor homocysteine removal.
3. Name some reactions that require methylation?
Synthesis of DNA, carnitine, creatine, epinephrine, purines, and nicotinamide.
4. What is a polymorphism?
Variation in a gene (thru DNA substitutions) that has effects on function of the enzyme it encodes.
5. What is the most studied MTHFR polymorphism?
C677T (thymine substitutes the normal cytosine at 677)
6. Which diseases are discussed by the author as possibly being associated with MTHFR polymorphisms (there are actually several others that are not mentioned like: cancers, depression, and osteoporosis)?
Neural tube defects (low folate), cardiovascular disease (low folate… and high homocysteine?), dementia (high homocysteine), colorectal cancer (low folate).
Day07-Guide07 - Leiber Lecture - Chronic Disease, Lifestyle, and Personalized Medicine
1. Explain why homozygote carriers of an FADS2 deletion allele do not benefit from alpha linolenic acid for reduction of metabolic syndrome risk.
ALA must be converted to EPA/DHA in order to be of health benefit. People without it cant make omega-3 needed.
2. Explain how Indole-3-carbinol can help alter estrogen metabolism to a more favorable estrogen metabolite profile.
Indole induces shunting of the pathway towards less carcinogenic metabolites.
3. How can someone with a GSTT1*1 SNP modify his/her risk for a myocardial infarction (heart attack)?
Eat cruciferous vegetables.
4. Amongst commonly accepted standard practices of medicine, approximately what percentage are of unknown effectiveness according to BMJ Clinical Evidence?
46%
5. For what clinical indication does CoQ10 have good scientific evidence?
For high blood pressure
6. For what clinical indications does alpha lipoic acid have strong scientific evidence?
Diabetes, improves blood sugars. Neuropathies associated w/ diabetes
7. For what clinical indications do probiotics have strong scientific evidence?
Ulcerative colitis, reverse antibiotic treatment, eczema, H. pylori.
8. Of fish oil , vitamin D, probiotics, alpha lipoic acid, supplementation with which has been shown to decrease all cause mortatlity?
Fish oil. (maybe vitamin D)
9. Name some ways that supplementation with nutrients could be used.
As a drug, based on specific disease orally or IV, For treatment of a deficiency, Overcome SNP, support the following – 1. phase2 detoxification 2. mitochondria function 3.insulin/glucose metabolism 4. endothelial function 5. Cancer cell apoptosis 6. hormone production 7. neurotransmitter function 8. GI balance. 9. Inflammation modulation
Day07-Guide08 - Rosenthal Lecture - Longevity and Wellness
1. What gene is turned on during 30% caloric restriction in animals? What food compound in pharmacological concentrations can activate this same gene and pathway in laboratory animals?
Gene = Sirtuin 1 (SIRT-1). Compound = Resveratrol
2. Do animals live longer and suffer less disease when on caloric restriction?
Yes.
3. What are the 3 leading causes of death according to the CDC?
1. Heart disease 2. Malignant neoplasms 3. Cerebrovascular disease
4. Does trans-fat redistribute adiposity in laboratory animals and or alter weight gain?
Yes. 30% more abdomen fat.
5. Is there evidence of a benefit in fatty fish consumption or fish oil supplementation following a myocardial infarction?
29% reduction in mortality in 2 yr f/u from all causes and 33% reduction in cardiac death with eating fatty REAL fish.10-15% reduction with fish OIL supplementation.
6. What is the outcome of the Lyon Diet (mediterranean) Heart trial and what type of diet was used?
70% overall reduction in mortality 73% reduction in nonfatal acute MI. 76% reduction in cardiac mortality.
7. What are the summary findings of the Diabetes Prevention trial? What precisely was the % of individuals that progressed to diabetes in the control group, drug group, and lifestyle change group?
Control = 1.0. Drug = 31% did not progress to DM compared to control. Lifestyle = 58% did not progress to DM compared to control.
8. What is the combined program that was proven in the Intensive Lifestyle Program for coronary artery disease reversal without medications? Did blood flow to the heart stabilize or improve in this study?
Ornish Diet? Blood flow improved.
9. What are some inflammatory and oxidative stress markers that improve on a Mediterranean diet?
CRP, IL-6, E-selectin, sICAM, sVCAM-1
10. Will adding nuts to a Mediterranean diet offer any benefit compared to olive oil for patients with metabolic syndrome?
Beginning of study = 61.4% had metabolic syndrome. 6.7% decrease w olive oil. 13.7% decrease w nuts instead of olive oil.
11. What are some beneficial compounds found in nuts that could reasonably confer benefit for cardiovascular risk?
Potassium, Fiber, Alpha-linolenic acid, Beta-tocopherol, Gamma-tocopherol
12. What 3 populations have been studied and have documented high numbers of centenarians?
Sardinia, Adventists (Loma Linda, CA), Okinawans
13. Can different carbohydrates activate different genes?
Yes. The FUNGENUT study found 71% down-regulated genes with rye pasta, including genes linked to insulin signaling and apoptosis (low insulin response=good). Oat-wheat-potato up-regulated 62 genes related to stress, cytokine mediated immunity, and interleukin pathway (hyperinsulin response)
14. What are the recommendations for cancer prevention from the WCRF (world cancer research fund) report?
10 things! Decrease 1. Body Fat 2. energy/sugars intake 3. Alcohol. 4. Processed meats. 5. Salt. 6. Mold cereals grains, or legumes (w/ aflatoxins > liver cancer). ALSO Increase 7. Exercise 8. Plant foods. 9. Nutrition via diet. 10. Breastfeeding.
15. What type of cancer has an association with high consumption of red meat? What compounds are formed when meat is heated to high temperatures?
Stomach Cancer, Heterocyclic Amines
16. What are some of the characteristics of foods eaten by Okinawans that may add to their longevity as compared to Americans (pie chart data)?
1) Omega-3 Foods = 11% vs. 1% (US). 2) Vegetables = 34% vs 16% 3) Flavonoids = 12% vs <1%
17. What type of cooking is best for broccoli to maintain its phenolic compounds?
Steaming (97% loss with microwaving)
18. Is there a relationship between omega-3 fatty acid intake and depression?
Decrease.
Day07-Guide09 - Foods Study Guide
1.      What vegetable has extremely high amounts of nutrients and is highest on the vegetable USDA ORAC scale? (see Dr. Rosenthal’s lecture)
Kale
2.      What is organic food and what is the minimum percent of organic food that must be contained in a product for it to carry the USDA organic seal on the front of the package?
Foods that are produced without pesticides, growth hormone, toxic fertilizers and antibiotics. Must be at least 95% organic. http://www.whfoods.com/organics.php
3.      What vegetable has the greatest ability to bind bile acids and lower cholesterol?
Collard greens  
5.      Should this food be steamed, boiled, grilled, or eaten raw for the greatest cholesterol lowering affect?
Steamed
6.      In what food family are collard greens, kale, mustard greens, broccoli, Brussels sprouts, cabbage?
Brassica / Cruciferous
7.      What category of cancer fighting compounds is found in these?
Glucosinolates
8.      What is the garlic’s most highly valued sulfur compound? What preparation method is ideal for retaining significant amounts of this compound? What mineral, essential for intracellular antioxidant status and critical for detoxification pathways, is garlic a good source of even when it is grown in soil with low concentrations?
Allicin, chop or crush the garlic before cooking or addition of acids, selenium
8. Garlic is a rich source of what mineral also required as a cofactor of the antioxidant superoxide dismutase?
Manganese
9. What fruit, analyzed by researchers at Tufts University, came out on top in its rating capacity to destroy free radicals.
Blueberries
10. What percent of daily value of vitamin C would be found in 1 cup of this fruit?
31.4 %
11. What antioxidant phytonutrients neutralize free radical damage to the collagen matrix of cells and tissues?
Anthocyanidins. They work their protective magic by preventing free-radical damage, inhibiting enzymes from cleaving the collagen matrix, and directly cross-lining with collagen fibers to form a more stable collagen matrix.
12. What effects have been demonstrated using this fruit in aging animals?
It improved both the learning capacity and motor skills of aging animals, making them mentally equivalent to much younger ones.
13. What is the effect the fruit’s compounds regarding E. coli and the urinary tract?
Components found in cranberry and blueberry juice reduce the ability of E. Coli, the bacteria that is the most common cause of urinary tract infections, to adhere.
What carotenoid concentrated in tomatoes has been studied for anticancer properties?
Lycopene
15. What are the summary findings from the 14-month study published in the J. of the National Cancer Institue comparing animals fed a carcinogen and testosterone, tomato powder, the isolated carotenoid as a supplement, compared to the control group? What about the subgroup that was calorie restricted? What about the meta-analysis of 21 human studies?
animals fed tomato powder plus a carcinogen had a 62% death rate of prostate CA, while 80% of animals in the control group died from prostate CA; in the diet that was calorie restricted, there was a 32% drop in risk of dying from prostate CA; in the meta-analysis of 21 human studies, eating raw tomatoes reduced the risk by 11%, cooked tomatoes by 19%
17. According to the Monterey Bay Aquarium Sea Food Watch pocket guide for the Southeast region of the US sort the following into “Best Choices” verses “Avoid” and note if they are placed in that category for contamination, overfishing, or poor fishery/environmental practices if it is specified – Lobster Spiny US; Tilapia Farmed US vs. Asia; Salmon (Alaska wild) vs. farmed Atlantic); Bluefin Tuna; Stone Crab; Swordfish; Grouper; Catfish farmed US; Atlantic Cod; Shrimp US, Canada vs. Imported. Keep the guide for future reference.
BEST – 1) Lobster spiny US, 2) tilapia US farmed, 3) salmon Alaska wild, 4) stone crab, 5) catfish US farmed, AVOID – 1) tilapia Asia (overfarmed), 2) Atlantic Cod (overfarmed), 3) Shrimp imported (overfarmed) 4) salmon farmed atlantic (contaminated/overfarmed), 5) tuna Bluefin (contaminated/overfarmed), 6) swordfish (contaminated/overfarmed), 7) grouper (contaminated/overfarmed), ALTERNATIVES – Shrimp of US and Canada
19. According to research done at Wake Forest University School of Medicine compare and contrast the fatty acid profiles of farm raised salmon, trout, tilapia, and catfish.
trout & salmon had high omega 3s compared to omega 6s with low SFAs & significant amounts of MUFAs & PUFAs; tilapia & catfish were the exact opposite
21. How does cooking method affect the atherosclerotic disease risk of fish consumption (even omega 3 rich fish)?
fried fish showed no cardiovascular benefit, even if it was a fish high in omega 3s, should bake, steam, or broil them (or eat them in sushi)
23. What percent of vitamin A is found in a baked sweet potato with skin? What is interesting about glycemic effect of sweet potato? What is one proposed mechanism for this effect?
it has on average, 35% of Vit A needs on average & 90% of vit A needed sometimes; sweet potatoes improve blood sugar regulation, it could be because sweet potatoes increase adiponectin, which helps regulate insulin metabolism - people with higher levels tend to have less insulin resistance
25. Where are the greatest concentration of polyphenols in walnuts found? What form of vitamin E is particularly beneficial and found in walnuts?
polyphenols in walnuts are found in the skin, they have the gamma-tocopherol form of vit E, which provides protection in heart problems
Day08-Guide01 - IM, Rakel - Ch. 86 Adverse Food Reactions and the Elimination Diet
1. Discuss the differences between Food Allergy and Food Intolerances?
Food allergy - immune-mediated (mainly IgE) reaction usually to a glycoprotein found in a given food, symptoms arise in minutes to hours, symptoms include rash, anaphylaxis, enteropathy and proctitis. Food intolerance, however, is any adverse physiologic response to a food product, may be due to the presence of a toxic contaminant or to pharmacologic properties of substances normally found in a food, cause may be influenced by IgG, hormonal changes, decreased intestinal permeability, alteration in inflammatory mediator levels, symptoms arise in hours to days
2. What type of cells help regulate intestinal immunity?
Epithelial cells of GI tract act as antigen-presenting cells because they sample various potential antigens. Also helping in this are gut dendritic cells and 5 types of T-cells which Allow tolerance to develop.
3. What is “leaky gut”? How can it contribute to symptoms of food intolerance?
greater intestinal permeability and is a means by which antigens typically unable to cross through intestinal tract into blood become capable of doing so.
4. What factors may contribute to increased intestinal permeability?
Inflammation, exposure to meds (NSAIDs), shifts in intestinal microflora and presence of various disease states
5. What is the gold standard test for establishing food allergy? What other testing is helpful to assess the presence of food allergies but not food intolerances?
Gold standard, double-blind, placebo-controlled food challenge (DBPCFC), requires IV access and food products and placebos can be difficult to prepare/mask. Other testing for allergy but not intolerance, radioallergosorbent testing (RAST) and skin-prick testing.
6. What is the diagnostic method of choice for suspected food intolerance?
Elimination diet
7. What other types of testing are mentioned for evaluating food intolerances but remain unproven or controversial? [of note: although large clinical trials have not been done to validate these testing methods, they seem to be very clinically useful)
IgG4 levels, applied kinesiology, patch testing, ALCAT
8. In children with genetic susceptibilities for attention deficit-hyperactivity disorder, to which food additives are these patients particularly vulnerable (e.g. those that are known to have direct physiologic effects on the central nervous system)?
Tartrazine (yellow #5), benzoates, flutamate
9. According to the test, what foods are most likely to trigger flares in atopic dermatitis in children?
Egg, milk, peanut, soy, wheat, tomato
10.  Regarding migraine headaches - What foods contain tyramine? Nitrates? Histamine?
Tyramine - aged cheeses, some red wines. Nitrates - processed meats. Histamine - fish, cheese, wine, beer
11.  What food additive may be high in preserved meats and Chinese food?
Preserved meats and Chinese food - monosodium glutamate
12. What artificial sweetener in particular should be eliminated for a trial period in a patient with migraine headaches?
Artificial sweetener - aspartame
13. What type of food in particular should be considered for removal from the diet in a child with chronic middle ear congestion and otitis media?
Dairy
14. Name the common conditions in which evidence most favorably supports use of an elimination diet?
Migraines, congestion, otitis media, diarrhea-predominant IBS
15. What are the steps of the elimination diet?
4 steps. 1) Planning - complete hx, dietary log, symptom description and timing, elicit a list of potential foods to avoid 2) Avoidance - different levels depending on amount of foods to eliminate, dependent on compliance and nutrition, most popular are moderate-elim because they have the greatest potential. Should follow for at least 10 days 3) Challenge - reintroduction of foods to see if they are the actual culprit and not a relapsing chronic condition. reintro every 3-4 days to allow sx to appear. food is eaten for only 1 day 4) Creation of long-term plan - can reintro food 3-6 mo later to see if intolerance still exists
16. What should patients be warned of when starting an elimination diet?
Symptoms may worsen before improving
17. In addition to any chronic symptoms the patient may have had prior to starting the elimination diet, what other symptoms may a patient experience when re-introducing foods to which he/she is intolerant?
Lung congestion, increased mucus production, fatigue, concentration difficulties, digestive problems, constipation and diarrhea, bloating, fluid accumulation, mood swings, drowsiness
18. What are some of the risk associated with the elimination diet?
Activate latent eating disorders, Increased sensitivity, anaphylactic reaction (so never reintro that one), Malnutrition, Increased cost, limited social engagement, Decreased enjoyment of eating, non-compliance
Day08-Guide02 - Adv Nut. Human Metab. - A. Fiber, Definitions, Fiber and Plants pp. 107-108. B. Physiological and Metabolic Effects of Fiber pp. 112-118. C. Roles of Fiber in Disease Prevention and Management pp.118-121
1. What are dietary fiber and functional fiber as defined by the National Academy of Sciences Food and Nutrition Board?
Nondigestable (by humans) carbohydrates and lignin that are intact and intrinsic in plants
2. What is cellulose and where is it found within plants?
Long glucose polymers found mostly within secondary plant wall (outer more structured and organized wall)
3. What is lignin and where is it found with in plants?
It is a highly branched polymer of phenol subunits. Lignan provides structural support to plants in specialized cells where lignan permeates thru intracellular spaces attaching to cell walls and even penetrating into them
4. What are several types of water-soluble fibers?
Some hemicelluloses, pectin, gums, beta-glucans
5. What are severely types of insoluble fibers?
Cellulose, lignin, some hemicelluloses, chitosan, chitin
6. What generalizations can be made about soluble as compared to insoluble fiber with regard to gastric emptying, intestinal transit time, nutrient absorptions, and fecal bulk?
Soluble fibers generally delay gastric emptying, increase transit time (thru slower movement in intestine), and decrease nutrient absorption while nonsoluble fiber increases fecal bulk and decreases transit time (faster movement).
7. Generally do vegetables, wheat, and other grains contain more insoluble or soluble fiber?
Insoluble
8. What attribute of fiber likely accounts for a feeling of postprandial satiety as well as slows down the digestion process when fiber intake is sufficient in a meal?
The viscous gels formed by soluble fiber slow gastric emptying. The increased time food remains in the stomach stimulates satiety and slows digestion, which is also further slowed by decreased enzyme function and lower intestinal speed as well.
9. What is the net effect of fiber intake on the blood glucose response and the hormonal response to a meal?
Attenuates the response thru decreased glucose absorption rates and lower blood glucose levels thereby decreasing GLP-1 and insulin response.
10. By what mechanisms does fiber intake affect blood glucose response to a meal?
the mechanism is basically decreased glucose diffusion both within the lumen and thru the mucous layer lining the lumen.
11. What is the effect of fiber intake on bile acid excretion?
Bile acid binds to fiber which prevents resorption and therefore increases colonic metabolism and subsequent excretion
12. What are the mechanisms/events by which consumption of fiber in the diet lower serum cholesterol concentrations?
Since cholesterol and bile salts bind to fiber and are excreted, less of both are absorbed which lowers hepatic levels of cholesterol which thereby allows greater LDL absorption into hepatocytes which require more cholesterol to replace the non resorbed bile salts. A second possible mechanism is fibers effect on reducing HMG CoA reductase activity (regulatory enzyme necessary for cholesterol production), which results in reduced cholesterol synthesis. A final proposed mechanism suggests that short chain fatty acids produced from microflora fiber metabolism inhibit fatty acid and cholesterol synthesis.
13. What affect do soluble fibers have on absorption of lipids?
They bind lipid and therefore decrease absorption
14. What is the effect of psyllium, guar gum, beta-glucan and oat products, pectin on serum cholesterol?
they lower serum levels
15. What effect do more rapidly fermentable fibers such as pectins and oligosaccharides have on mineral balance as compared to less fermentable fibers?
More fermentable fibers have positive effect on mineral balance (more absorption).
16. What are the gastrointestinal responses to rice bran or wheat bran intake?
These are more insoluble fibers, they have less lipid lowering effects for example
17. What are prebiotics and how do fermentable fibers act as prebiotics?
Prebiotics stimulate probiotic production. While not expressly stated how in the book, I suppose they preferentially provide energy to (are digested by) probiotic microflora.
18. What is the effect of fructans/fructooligosaccharides in the diet on the growth of bifidobacteria and lactobacilli?
Stimulate growth
19. What are some general effects of short-chain fatty acids generated from fermentation of dietary fiber and what specific short chain fatty acid provides an energy source for colonic epithelial cells?
Increased water and sodium resorption, mucosal cell proliferation, provision of energy, acidification of luminal environment.
20. What “health claim” approved by the FDA is associated with beta-glucan from oat bran, rolled oats, or oatmeal, and also psyllium husk?
May reduce the risk of heart disease.
21. With regard to the incidence of gastrointestinal disorders, heart disease, and breast and colon cancers, what have populations studies concluded regarding fiber intake?
They have a lower incidence
22. Adequate intake of soluble, nonfermentable fiber has been recognized as important in treating which gastrointestinal diseases?
Colon, colorectal cancer.
23. What are some of the mechanisms proposed for fiber’s preventive role against colon cancer?
Decreased bile acid levels, lower carcinogens in lumen by increased fecal bulk, decreased time of toxin production and exposure with increased transit speeds, binding of carcinogens for excretion, pH lowering effect of SCFA’s increases available Ca which offsets mitogenic advantage of cancer cells.
24. What is the AI range for fiber (children under 3 to men over 50)? Use table 4.2.
Kids 1-3yrs, 19g. 4-8yrs, 25g. Males 9-13 yrs AND 51 and up, 31g. 14-50 yrs, 38g. Females 9-18yrs, 26g. 18-50yrs, 25g. 51 and up, 21.
25. Which foods are encouraged to increase fiber intake and are consistent with the USDA recommendations?
Fiber rich legumes, fruits and veggies, whole grains
26. You are not responsible for memorizing the specific numbers in grams of fiber per serving, however, note the following relative differences for the following (using table 4.3 on page 121): bold has more: white rice compared to brown rice, white bread compared with whole grain bread, watermelon with strawberries. Which group, fruits legumes, vegetables, or nuts provides the most fiber per serving size?
Legumes/Beans
Day09-Guide01 - Chapter 2 The Cancer Process AND Food, Nutrition, Physical activity and the Prevention of Cancer a Global Perspective, World Cancer Research Fund & American Institute for Cancer Research Summary Report and Link
1. What is the purpose of this introductory chapter?
The purpose is to summarize current knowledge and thinking on the biology of the cancer process, with special reference to food and nutrition, physical activity, and body composition.
2. Why is unraveling links between diet and cancer complex?
thousands of dietary components are consumed each day, and a typical diet may provide more than 25000 bioactive food constituents. The response is further complicated since a single, bioactive food constituent can modify multiple steps in the cancer process. Normal and cancer cells also differ in their responses to bioactive components in terms of the dose, timing, and duration of exposure required to bring about effects.
3. Why as a new field of study does nutrigenomics have profound implications in cancer prevention and therapy?
it seeks to clarify the impact of nutrition in the maintenance of genome stability and to dissect out the influence of genotype in determining our response to diet.
4. What effect do butyrate, allium vegetables, and sulphoraphane from cruciferous vegetables have on histones and DNA?
Butyrate, produced in the colon by bacterial fermentation of non-starch polysaccharide, diallyl disulphide from garlic other allium vegetables, and sulphoraphane, a glucosinate from cruciferous vegetables can ALL behave as histone deacetylase inhibitors (HDAI) and act to maintain DNA stability or enhance transcription.
5. What is methylation of DNA and what is its basic purpose?
Methylation is the addition of a methyl group and its main purpose is gene silencing. It occurs only to cytosine residues located next to guanine bases in the DNA sequence. Transcription factors cannot bind these sites when methylated and so the gene is silenced.
6. Intake of what vitamin found in green leafy vegetables is an important determinant of normal methylation?
Folate is found in green leafy vegetables and functions as a coenzyme in the metabolism of single-carbon compounds for nucleic acid synthesis and amino acid metabolism.
7. What effect related to cancer, demonstrated in a systematic review, do long chain n-3 PUFAs have on colonic epithelium?
Long-chain n-3 PUFAs in fish oils promote differentiation of colonic epithelial cells.
8. Nucleotide excision repair has been found to be lower in adults with the lowest intake of what nutrient?
Folate
9. What evidences exists in exfoliated colonocytes for benefit of a vegetarian diet compared to a diet high in meat?
The amount of single-strand breaks in exfoliated colorectal mucosal cells was significantly lower in healthy individuals consuming a vegetarian diet compared with a diet high in meat.
10. How might vitamins C, E, and dietary polyphenols protect against cancer risk?
Vitamins C and E donate electrons to the free radicals and block their damaging activity. Dietary constituents such as ITCs and polyphenols can also activate the signaling pathways that lead to activation of the antioxidant response element and upregulation of the expression of detoxifying enzymes.
11. How can chronic inflammation result in DNA damage and cancer promotion?
Chronically inflamed tissue is infiltrated with a variety of inflammatory cells that produce a wide variety of bioactive chemicals. These include cytokines, growth factors, reactive oxygen and nitrogen species, cyclooxygenase, and lipoxygenase products. A chronic inflammatory environment can increase proliferation and differentiation, inhibit apoptosis (programmed cell death), and induce angiogenesis (generation of new blood cells).
12. What hormones are elevated in obese people and can promote cancer cell growth?
IGF-1, insulin, and leptin
13. How is hyperinsulinemia associated with a risk of cancer?
Hyperinsulinemia increases the risk of cancers of the colon and endometrium, and possibly of the pancreas and kidneys.
14. How does obesity affect sex steroid hormones and influence cancer?
Adipose tissue is the main site of estrogen synthesis in men and postmenopausal women. The increased insulin and IGF-1 levels that accompany body fatness results in increased estradiol in men and women, and may also result in higher testosterone levels in women. Increased levels of sex steroids are associated with the risk of endometrial and postmenopausal breast cancers, and may impact on colon and other cancers.
15. Why is obesity considered a low-grade chronic inflammatory state?
Up to 40% of fat tissue is comprised of macrophages. Adipocytes produce pro-inflammatory factors, and obese individuals have elevated concentrations of circulation TNF-a, IL-6, and C-reactive protein, compared to lean people, as well as of leptin, which also functions as an inflammatory cytokine. Such chronic inflammation can promote cancer development.
16. What types of carcinogenic compounds are formed during food preparation such as cooking meat at high temperatures?
Cooking meat at high temperatures forms heterocyclic amines, and polycyclic aromatic hyrdocarbons can be produced in meat and fish that has been grilled (broiled) or barbecued (charbroiled) over a direct flame.
17. From what foods are N-nitroso carcinogens derived in the diet?
N-nitroso compounds are carcinogens, and are formed in foods containing added nitrates or nitrites. For example, fish and meat preserved with salting or preservatives, and smoking or drying. N-compounds are also produced endogenously in the stomach and colon of people who eat large amounts of red meat or take nitrite supplements.
18. How long after initial DNA damage do most cancers develop to the stage of being clinically identifiable?
Years or decades after
19. How do retinoids and carotenoids affect cell proliferation of initiated cells?
Retinoid and carotenoids inhibit proliferation by binding retinoid receptors on the cell surface. Retinoids can also inhibit proliferation of initiated cells by inducing apoptosis or inducing differentiation of abnormal cells back to normal.
20. In what manner do phenolic compounds such as EGCG from green tea affect cell cycle and angiogenesis (increase or decrease)?
can inhibit some cyclins and cyclin-dependent kinases (thus decrease).
21. In what vegetables are glucosinolates found and by what mechanisms can they decrease cancer risk?
Glucosinates, found in cruciferous vegetable, are converted in the liver to ITCs, which can arrest cell cycle progression, as well as induce phase 2 enzymes, which can promote carcinogen excretion.
22. Do animals fed fish oil supplements or n-3 fatty acids compared to corn oil have fewer or greater numbers of tumors, and of which type of tumors do they have?
They have fewer colonic tumors than those fed with a diet supplemented with corn oil due to dietary fiber-altering, fatty-acid binding, protein expression in colonocytes during tumor development. They have tumors of colorectal cancer.
23. What is the effect of restriction of energy intake from food on preventing cancer in experimental animals?
It increases the lifespan of rodents, and suppresses tumor development in mice. In addition, energy restriction can suppress the pro-cancer effects of many carcinogens in experimental animal models.
24. What are the projections for the rates of cancer in general and what patterns have emerged from the literature?
Increase. Studies consistently show that patterns of cancer change as populations migrate from one part of the world to another and as countries become increasingly urbanized and industrialized.
25. Cancer is a disease of genes vulnerable to mutation over lifespan. Evidence shows that only a small proportion of cancers are inherited. What factors are most important in determining cancer risk?
Environmental factors are most important and can be modified. These include smoking and other use of tobacco, infectious agents, radiation, industrial chemicals and pollution, medication, and also many aspects of food, nutrition, physical activity, and body composition.
26. What is the justification for recommendation 1 “Be as lean as possible within the normal range of body weight”?
most important ways to protect against cancer. This will also protect against a number of other common chronic diseases.
27. Why is it recommended to limit consumption of energy dense processed foods and sugary drinks?
Food supplies that are mainly made up of processed foods, which often contain substantial amounts of fat or sugar, tend to be more energy-dense and overconsumption can lead to overweight and obesity
28. Do sugary drinks induce satiety or a compensatory reduction in subsequent energy intake?
No, Because of their water content, drinks are less energy-dense than foods. However, sugary drinks provide energy but do not seem to induce satiety or compensatory reduction in subsequent energy intake, and so promote overconsumption of energy and thus weight gain
29. What is the recommendation regarding plant foods and why?
1) Eat at least five portions/servings (at least 400 g or 14 oz) of a variety of non-starchy vegetables and of fruits every day 2) Eat relatively unprocessed cereals (grains) and/or pulses (legumes) with every meal 3) Limit refined starchy foods 4) People who consume starchy roots or tubers as staples also to ensure intake of sufficient non-starchy vegetables, fruits, and pulses (legumes) WHY? 1) Do this because they are high in nutrients, 2) high in dietary fibre (and so in non-starch polysaccharides), and 3) low in energy density. 4) probably protect against some cancers. Being typically low in energy density, they probably also protect against 5) weight gain
30. What is the recommendation regarding beef, pork, and lamb? What is the recommendation regarding salted, or chemically preserved processed meat?
People who eat red meat to consume less than 500 g (18 oz) a week, very little if any to be processed.
31. What is the recommendation regarding alcoholic drinks?
If alcoholic drinks are consumed, limit consumption to no more than two drinks a day for men and one drink a day for women
32. What is the report’s finding and recommendations regarding consumption of salt?
1) decrease salty foods. 2) less than 6 g (2.4 g sodium) a day 3) they cause stomach cancer.
33. What are aflatoxins? What foods are they associated with and what type of cancer?
1) Aflatoxins are naturally occurring 2) mycotoxins that are produced by many species of 3) Aspergillus. Contamination of 4) cereals (grains) and 5) pulses (legumes) with aflatoxins, produced by some moulds when such foods are stored for too long in warm temperatures, is an important public health problem and can lead to 6) liver cancer.
34. What is the report’s recommendation regarding high-dose nutrient supplements as compared to consumption of the relevant nutrients through the usual diet?
Aim to meet nutritional needs through diet alone. Dietary supplements are not recommended for cancer prevention, they could be preventative or could be causative of cancer
35. What is the recommendation regarding breastfeeding? What are the benefits to the mother, and to the infant?
1) Aim to breastfeed infants exclusively up to six months and continue with complementary feeding thereafter. 2) Prevents breast cancer in mothers and to prevent overweight and obesity in children 3) Breastfeeding protects against infections in infancy, protects the development of the immature immune system, protects against other childhood diseases, and is vital for the development of the bond between mother and child. 4) Also vital where supplies of water are diminished or compromised
36. What are the recommendations for cancer survivors?
All cancer survivors to receive nutritional care from an appropriately trained professional, get diet, healthy weight, and physical activity.
Is this Pro or Anti cancer? > N-nitroso compounds
PRO!
Is this Pro or Anti cancer? > polychlorinated biphenyls
PRO!
Is this Pro or Anti cancer? > heterocyclic amines
PRO!
Is this Pro or Anti cancer? > Obesity
PRO!
Is this Pro or Anti cancer? > Afltoxins
PRO!
Is this Pro or Anti cancer? > Insulin like growth factor
PRO!
Is this Pro or Anti cancer? > Selenium
ANTI!
Is this Pro or Anti cancer? > Indole-3-carbinol
ANTI!
Is this Pro or Anti cancer? > Curcumin
ANTI!
Is this Pro or Anti cancer? > Flavonoids
ANTI!
Is this Pro or Anti cancer? > n-3 PUFA
ANTI!
Is this Pro or Anti cancer? > Energy restriction
ANTI!
Is this Pro or Anti cancer? > Phase II enzymes
ANTI!
Is this Pro or Anti cancer? > Organosulfur compounds
ANTI!