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Nutrition in Health and Wellness Donald I. Abrams, M.D. Chief, Hematology-Oncology San Francisco General Hospital Integrative Oncology UCSF Osher Center for Integrative Medicine Professor of Clinical Medicine, UCSF 14 Components of Dietary Risk • Diets low in: – Fruits – Vegetables – Whole grains – Nuts and seeds – Milk – Fiber – Calcium – Seafood omega 3s – PUFA’s • Diets high in: – Red meat – Processed meat – Sugarsweetened beverages – Trans fatty acids – Sodium Lim et al, Lancet 2012 Proportion of Cancer Deaths Caused by Different Avoidable Cancers Causes Percent 1981(US)* Percent 1998(UK)** Tobacco 25-40 29-31 Diet 10-70 20-50 Medicines 0.3-1.5 <1 Infection: parasites, bacteria, viruses 10 10-20 Ionizing and UV light 2-4 5-7 Occupation 2-8 2-4 Pollution: air, water, food <1-5 1-5 Physical inactivity * Doll and Peto, 1981; ** Doll, 1998 1-2 Diet and Cancer • Probably involved in 30-35% of all cancers • Certainty about diet less firm than tobacco – Contradictory study results i.e. fiber – Hard to define what the diet actually is • Diets are very complex • Diets vary over time • Is it what we ate in the past? Or perhaps what our mothers ate? Or theirs? ACS and WCRF/AICR Guidelines WEIGHT GUIDELINES •Maintain a healthy weight throughout life •Balance caloric intake with physical activity •Avoid excessive weight gain throughout the life cycle •Achieve & maintain a healthy weight if currently overweight or obese Be as lean as possible without becoming underweight Obesity Trends* Among U.S. Adults BRFSS, 2010 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% Source: Behavioral Risk Factor Surveillance System, CDC. 25%–29% ≥30% Obesity-Associated Malignancies • Breast (postmenopausal) • Endometrium • Prostate • Kidney • Colon • Esophagus • Pancreas • Gallbladder AICR report estimates that obesity-related excesses of these 7 cancers account for approx 115,000 preventable deaths a year in the US Body Fat Increases CA Risk • Body fat secretes cytokines that promote inflammation • Fat increases estrogen production • Increase in body fat may impair immunity • Too much body fit triggers insulin resistance, raising levels of insulin and growth factors that promote cancer ENERGY DENSE FOODS GUIDELINES Choose foods and beverages in amounts that help achieve & maintain a healthy weight •Avoid sugary drinks •Limit consumption of energy dense foods •Particularly processed foods high in added sugar, low in fiber or high in fat How can anyone consume that much sugar??? PLANT-BASED GUIDELINES •Consume a healthy diet, with an emphasis on plant sources •Eat 5 or more servings of a variety of fruits and vegetables each day; every meal and snacks •Choose whole grains in preference to refined Eat more of a variety of vegetables, fruits, whole grains and legumes U.S. Diets Fall Short on F&Vs • CDC reports only 14% of adults eat recommended number of servings/day – 33% eat 2 or more servings of fruit a day – 27% eat 3 or more servings of vegetables • DC 20.1%, VT, ME, HI, MA top 5 • WV, SD, AL, OK/SC, MS 8.8% rank last • Only 9.5% of high school students meet recommendations (32% fruit, 13% veg) • Healthy People 2010 objective was to have 75% meet fruit and 50% vegetable Centers for Disease Control 2009 Antioxidant Rich Foods • • • • • Fruits Vegetables Nuts Grains Some meat, fish and poultry The Benefits of Organic Food • Produce – Less exposure to pesticides – Same macronutrients but increased vitamin C, minerals and antioxidant phytonutrients – Often fresher because no preservatives – Organic farming better for environment • Animals – Not given antibiotics, growth hormones, or fed animal byproducts Nutritional Prevention Strategies Eat More: • Phytoestrogens – Soy foods – Flaxseed (Omega 3’s) • • • • Cruciferous vegetables Garlic and onions Turmeric and ginger Green tea Sulforaphane in Prostate Cancer • Sulforaphane is a constituent of cruciferous vegetables such as broccoli • CVs strongly associated with lower CaP • Preclinical studies suggest sulforaphane inhibited histone deacetylase (HDAC) function and suppresses androgen receptor signalling • GSTM1 gene contributes to sulforaphane metabolism Alumkal et al, ASCO 2013 Sulforaphane in Prostate Cancer • 20 men with CaP and PSA recurrence despite surgery or radiation • Treated with sulforaphane 200 umol/day • 16 patients completed 20 weeks – 1 had a PSA decline >50% – 7 had PSA declines 3-20% – 3 had final PSA less than baseline • PSA doubling time ↑’ed from 6 to 9.4 mos Alumkal et al, ASCO 2013 Sulforaphane in Prostate Cancer • “The compound we used is limited by not having several species toxicity, which will be necessary prior to dose escalation.” • “Groups are working on developing a synthetic version with druglike properties.” • “There are also OTC preparations,but I am not familiar with their quality control.” – Joshi J. Alumkal, MD, OHSU, Portland, OR June 2013 www.cancernetwork.com F&V and Colorectal Cancer • 85,903 men and 105,108 women 45-75 yo in Hawaii and California followed 7 years • Detailed questionnaires on dietary habits • 2110 participants developed CRC (1138 men) – For men, high levels of F&V associated with lower risk across 5 ethnic groups studied (RR- 0.74 [0.59,0.93]) – For women, no risk reduction seen for F&V – Risk reduction colon CA > rectal CA in men • Intake of grains had no effect in either sex Nomura et al Am J Clin Nutr 2008 Green Tea: Human Studies • Animal studies: Green tea has a protective effect against tumors of the colon, prostate, esophagus, liver, stomach, lung, breast, pancreas and skin • Iowa Women’s Health Study- catechin intake from tea was associated with a lower incidence of digestive tract cancers. • Chinese tea drinking men have half the risk of developing stomach or esophageal cancer, and have significantly lower risk of prostate cancer. Mushrooms and Green Tea • Case control study in SE China 2004-2005 • 1009 women with confirmed breast CA and 1009 age-matched controls – Compared with non-consumers • OR- 0.36 (95% CI 0.25, 0.51) for daily intake >10g fresh mushrooms • OR- 0.53 (95% CI 0.38, 0.73) for daily intake > 4 g dried mushrooms • ORs 0.11 and 0.18 for fresh and dried in combo with >1.05 g dried green tea leaf beverages/day – Effects seen in pre and post-menopausal women Zhang et al, Int J CA, 2009 Agaricus species • Agaricus blazei most common CAM Rx in Japanese cancer patients • Agaricus bisporus may have aromatase inhibitor activity – Significance of agaritine in raw button mushrooms unclear – ALL mushrooms must be cooked before eating !!! Turmeric- The Anticancer Spice • Purported properties – Antioxidant – Anti-inflammatory – Chemopreventive – Antimutagenic – Anticarcinogenic – Antimetastatic – Antiangiogenic – Cardioprotective RED MEAT GUIDELINES Limit consumption of processed and red meats Limit consumption of red meats (beef, pork and lamb) and avoid processed meats Meat Intake and Colon Cancer Armstrong and Doll, 1975 in Willett, 1995 Omega 3 vs Omega 6 Fatty Acids Transformation of food chain x20 Omg-6 /Omg-3 x15 x10 x6 Ailhaud et al., Prog. Lip. Res., 2006 – Simopoulos & Salem. NEJM, 1989 Fats, Fatty Acids and Prostate CA • Preclinical studies had suggested that ↓ dietary fat and ↓ n-6:n-3 lowers risk and slows progression of prostate cancer • 48 men undergoing radical prostatectomy • Randomized to low fat (15%) diet and 5 gm fish oil (n-6:n3 2:1) or control Western diet (40% fat, n6:n3 15:1) for 4-6 wks pre-op • Food prepared by UCLA chefs • Serum IGF-1 levels selected as primary Aronson et al, 2011 endpoint Fats, Fatty Acids and Prostate CA • No effect on serum IGF-1 levels • Low fat, high n-3 group had: – Lower omega-6:omega-3 ratios in blood and prostate – Less prostate tissue (benign and malignant) – Reduced cancer cell proliferation (Ki-67 index) – Reduced prostate cancer cell proliferation in vitro with their blood added c/w controls Aronson et al, 2011 Meat and Colorectal Cancer • Total iron intake and dietary iron both inversely associated, although the more bioavailable heme iron was positively associated • Nitrate intake from processed meat positively associated; nitrite not (p=0.055) • Heterocyclic amine intake (MeIQx and DiMeIQx) positively associated but only associated with colon, not rectal CA Cross et al, Cancer Res 2010 Dietary Fat and Pancreatic CA • NIH/AARP study, 6.3 yrs f/u 525K→ 1337 cases • Pancreatic cancer risk directly related to the intake of: – Saturated fat 51.5 vs 33.1 cases/100K py • HR= 1.36 (1.14,1.62; Ptrend<.001) – Monounsaturated fat 46.2 vs 32.9 cases/100K py • HR= 1.22 (1.02,1.46; Ptrend=.05) – Strongest associations for saturated fat from animal sources 52 vs 32.2 cases/100K py • HR= 1.43 (1.20,1.70; Ptrend<.001) • Specifically, intakes from red meat (HR=1.27) and dairy products (HR=1.19) were both associated with increased risk Thiebaut et al, JNCI 2009 Chemopreventive Components of Dairy • Dairy products contain – Calcium – Vitamin D – Butyric acid – Conjugated linoleic acid – Sphingolipids – Probiotic bacteria in fermented products The Problem With Dairy Lactose and Lactase-Who Is Lactose Intolerant and Why? Most animals lose milk-digesting enzymes after weaning, so lactose intolerance becomes the norm Montgomery, Robert K; Krasinski, Stephen D; Hirschhorn, Joel N; Grand, Richard J Journal of Pediatric Gastroenterology and Nutrition. 45():S131-S137, December 2007. doi: 10.1097/MPG.0b013e31812e68f6 FIG. 3. Developmental patterns (transcriptionally regulated) of lactasephlorizin hydrolase expression in humans and other mammals. Schematic diagram of developmental changes in lactase-specific activity changes from fetal life through birth and weaning. Copyright © 2011 Journal of Pediatric Gastroenterology and Nutrition. Published by Lippincott Williams & Wilkins. 45 Barbara Kingsolver on Dairy • “A few isolated populations developed intimate relationships with their domestic populations” leading to adaptation to keep lactose-digesting enzymes past childhood • Genetic mutation (SNP C/T13910) causes lactase persistence into adulthood (lactasephlorizin hydrolase gene) • LPH gene rapidly increased in herding populations Kingsolver, Animal, Vegetable, Miracle, 2007 Lactose and Lactase-Who Is Lactose Intolerant and Why? Lactose and Lactase-Who Is Lactose Intolerant and Why? Montgomery, Robert K; Krasinski, Stephen D; Hirschhorn, Joel N; Grand, Richard J Journal of Pediatric Gastroenterology and Nutrition. 45():S131-S137, December 2007. doi: 10.1097/MPG.0b013e31812e68f6 LNP- lactase nonpersistent LP- lactase persistent TABLE 1. Lactase phenotypes in selected human populations Copyright © 2011 Journal of Pediatric Gastroenterology and Nutrition. Published by Lippincott Williams & Wilkins. 47 Other Dairy Associations • Positive association prostate, ovarian and breast; protective in colorectal CA » Shrier et al, Nutr Cancer 2008 • Borderline positive association between cheese intake and bladder CA in Belgium » Brinkman et al, Eur J CA 2010 • Increased HR for death in ovarian CA observed for prediagnosis milk (all types) subgroup [HR 2.15, 1.20,3.84, p<0.05] » Dolecek et al, J Am Dietetic Assn 2010 My Standard Recommendations • Increase plant based foods – Whole grains – Fruits (deep pigment) and vegetables (cruciferous) • Decrease animal fats – Eliminate dairy, red and processed meats – Poultry preferably organic – Increase marine omega-3’s • Decrease refined carbohydrates – Sugar, white flour, white rice • Season with garlic, ginger, onions, turmeric • Drink green tea and red wine The doctor of the future will give no medicine, but will interest his patients in the care of the human body, in diet, and in the cause and prevention of disease. Thomas Edison 1847-1931 Let your food be your medicine And your medicine be your food Hippocrates