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CURRENT ISSUES IN CLINICAL NUTRITION Robert B. Baron MD MS Professor and Associate Dean UCSF School of Medicine Declaration of full disclosure: No conflict.

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Presentation on theme: "CURRENT ISSUES IN CLINICAL NUTRITION Robert B. Baron MD MS Professor and Associate Dean UCSF School of Medicine Declaration of full disclosure: No conflict."— Presentation transcript:

1 CURRENT ISSUES IN CLINICAL NUTRITION Robert B. Baron MD MS Professor and Associate Dean UCSF School of Medicine Declaration of full disclosure: No conflict of interest

2 Selected Topics Vitamin, mineral and fish oil supplements Low-fat diets Diet and lipid disorders Diet, exercise and weight loss

3 Case 1 53 year old woman in for check up. In good health. Exercises regularly. Eats low fat diet. Grandmother had hip fracture at age 86. Father with MI age 72. On no meds, but takes multivitamin and calcium daily. BMI 26. BP normal. LDL <100. What advice should you give about her diet and supplements?

4 Jackson, NEJM 2006 CALCIUM, VITAMIN D AND FRACTURES 36,282 postmenopausal women, 50-79 Randomized to 1000 mg calcium plus 400 IU of vitamin D vs placebo, 7 year f/u. Calcium/D Placebo Hazard Ratio Hip175 199 0.88 (0.72-1.08) Vertebral181 197 0.90 (0.74-1.10) Arm/wrist565 557 1.01 (0.90-1.14) Total2102 2158 0.96 (0.91-1.02)

5 Wactawski-Wende, NEJM 2006 CALCIUM, VITAMIN D AND INVASIVE COLON CANCER 36,282 postmenopausal women, 50-79 Randomized to 1000 mg calcium plus 400 IU of vitamin D vs placebo, 7 year f/u. Calcium/D Placebo Hazard Ratio Cancer168 154 1.08 (0.86-1.34)

6 Prentice, NEJM 2006 LOW-FAT DIET AND INVASIVE BREAST CANCER 48,835 postmenopausal women, 50-79 Randomized to dietary intervention or comparison Intervention: reduce total fat to 20% of energy and increase fruits and vegetables to at least 6 servings per day; 8.1 year f/u. Intervention Comparison Difference Between Groups Year 1Year 1 Year 3 Year 6 Fat24.3% 35.1% -9.5% -8.1% Calories1500 kcals 1594 kcals -93 -119.9 F and V5.1 servings 3.9 servings +1.3 +1.1 Weight 74.4 kg 76.3 kg -1.3kg -0.8kg

7 Prentice, NEJM 2006 LOW-FAT DIET AND INVASIVE BREAST CANCER (Cases, annualized per cent) Intervention Comparison HR p Breast Cancer Incidence 0.42 0.450.91 (0.83-1.01).09 Mortality 0.02 0.02 0.77 (0.48-1.22).27 Total Cancer Incidence 1.23 1.28 0.96 (0.91-1.02).10 Mortality 0.28 0.29 0.95 (0.84-1.07.22 Total mortality 0.60 0.61 0.98 (0.91-1.07).29

8 Cummulative Hazard Time, y LOW-FAT DIET AND INVASIVE COLON CANCER Beresford, S. A. A. et al. JAMA 2006;295:643-654. HR, 1.08 (95% Cl,0.90-1.29) Weighted Log-Rank P=.29

9 Howard, B. V. et al. JAMA 2006;295:655-666. LOW-FAT DIET AND CARDIOVASCULAR DISEASE Time, y Cummulative Hazard Time, y Cummulative Hazard Participants Without a History of CVD All Participants

10 Howard, B. V. et al. JAMA 2006;295:39-49. LOW-FAT DIET AND WEIGHT CHANGE Mean Difference, kg Overall

11 Case 2 63 year old man, with CAD, s/p angioplasty with stent placement, feels well, in for check up. Meds include ASA, beta blocker, ACE, statin, thiazide, vitamin E, beta-carotene. He asks whether he should start B vitamins and fish oil.

12 Eidelman, JAMA, 2004 VITAMIN E AND CARDIOVASCULAR DISEASE Vitamin E vs placebo 7 RCTs; 106,625 subjects CV eventCV death MI Stroke Vit E 4832 26831255 742 Placebo 4895 26891254 723 NS NS NS NS

13 Hope and Hope-TOO Investigators, JAMA, 2005 VITAMIN E, CARDIOVASCULAR EVENTS AND CANCER: HOPE TOO 3994 subjects, >55, vascular disease or diabetes Randomized to 400 IU vitamin E, or placebo, 7 year f/u Vitamin E Placebo p Cancer552586.30 Cancer deaths156178.24 CV events1022985.34 Heart failure641578.03 Hosp for CHF236196.045

14 Lee, JAMA, 2006 VITAMIN E AND CARDIOVASCULAR DISEASE AND CANCER Womens Health Study, Vitamin E 600 IU QOD vs placebo 39,876 subjects, over 45 years old, 10.1 yrs f/u Vitamin E Placebo p CV event482517 0.26 MI1961950.96 Stroke2412460.82 CV deaths106140 0.03 Invasive cancer143714280.87 Total mortality636615 0.53

15 Vivekananthan, Lancet, 2003 Beta-CAROTENE AND CARDIOVASCULAR DISEASE Beta-carotene vs placebo 8 RCTs; 138,113 subjects MortalityCV death Stroke Carotene 7.3% 3.3%2.4% Placebo 7.0% 3.1%2.3% NNH* 326 409 NS * number needed to harm

16 Lange, NEJM, 2004 FOLATE AND RESTENOSIS AFTER STENTING 636 patients, post stent Randomized to folic acid, B6 and B12 vs placebo, 6 month f/u Restenosis Lumen Revasc B vitamins 35.5% 1.59mm 15.8% Placebo 26.5% 1.74mm 10.6% p=0.05 p=0.008 p=0.05

17 Toole, JAMA, 2004 VITAMIN INTERVENTION FOR STROKE PREVENTION (VISP) 3680 adults, s/p stroke Randomized to: Mulitivit with low dose B6, B12, folic acid Multivit with high dose B6, B12, folic acid Stroke CHD DeathCombined Low dose 148 123 117 316 High dose 152 114 99 303 p=0.80 p=0.57 p=0.25 p=0.61

18 Bonaa, NEJM, 2006 HOMOCYSTEINE LOWERING AND CARDIOVASCULAR EVENTS (NORVIT) 3749 men and women post MI Folic acid (0.8 mg), B12 (0.4 mg), and B6 (40 mg) vs. placebo; 2 X2 factorial design; 40 month f/u B Vitamins/Placebo p Combined events1.22 0.05 MI1.230.06 Stroke0.83 0.52 Cancer1.02 0.94 Total mortality1.21 0.19

19 HOPE 2, NEJM, 2006 HOMOCYSTEINE LOWERING AND CARDIOVASCULAR EVENTS (HOPE 2) 5522 men and women with vascular disease or diabetes 55 and older; 5 year f/u Folic acid (2.5 mg), B12 (1 mg), and B6 (50 mg) vs. placebo B Vitamins/Placebo RR p Combined events 0.95 0.41 CV Death 0.960.59 MI 0.980.82 Stroke 0.750.03 Total mortality 0.99 0.94

20 Raitt, JAMA, 2005 FISH OIL AND SUDDEN DEATH Background: Observational data (Eskimos) and 4 RCTs suggest reduced sudden death with fish oils (diet or supplement) RCT, 200 patients with implantable defibrillators, fish oil 1.8g vs placebo, for two years

21 Raitt, JAMA 2005 Time to First Episode of ICD Therapy by Fish Oil vs Placebo Group

22 MacLean, JAMA, 2006 OMEGA-3 FATTY ACIDS AND CANCER Systematic review of 38 studies 20 cohorts, 11 types of cancers: Breast: 1 increased, 3 decreased, 7 no association Colon: 1 decreased, 17 no association Lung: 1 increased, I decreased, 4 no association Prostate: 1 decreased, 15 no association Skin: 1 increased Aerodigestive, bladder, lymphoma, ovarian, pacreatic, and stomach: no association

23 Case 2 63 year old man, with CAD, in for check up. Plan: DC vitamin E and carotene Defer B vitamins and fish oil Reinforce use of current meds, diet (including fish) and exercise

24 Case 3 53 year old woman, in good health, in for check up. No cardiovascular risk factors. Body mass index is 26. BP 110/70. LDL- cholesterol is 170, HDL-cholesterol is 55, triglycerides 100. She exercises 5 days per week. Follows low fat, low cholesterol, mostly natural food diet. Framingham risk score 1% risk of CV event in next 10 years How should we manage her LDL?

25 LDL Goal and Cutpoints Patients with 0–1 Risk Factor 2001 and 2004 190 mg/dL (160–189 mg/dL: LDL-lowering drug optional) 160 mg/dL <160 mg/dL LDL Level at Which to Consider Drug Therapy LDL Level at Which to Initiate Diet LDL Goal

26 ATP III, NCEP 2001 Therapeutic Lifestyle Changes (TLC): Major features TLC Diet –Reduced intake of cholesterol-raising nutrients Saturated fats <7% of total calories Dietary cholesterol <200 mg per day –LDL-lowering therapeutic options Plant stanols/sterols (2 g per day) Soluble fiber (10–25 g per day) Weight reduction Increased physical activity

27 TLC for patients with LDL-C = 160 Dietary Component LDL-C (mg/dL) Low saturated fat/dietary cholesterol –12 Viscous fiber (10–25 g/d) –8 –8 Plant stanols/sterols (2 g/d) –16 Total –36 mg/dl –36 mg/dl

28 Gardner, Ann Intern Med, 2005 EFFECT OF A PLANT-BASED DIET 120 patients, LDL 130 - 190, 4 weeks Low fat vs. low fat plus Equivalent macronutrients Low-fat plus had more vegetables, legumes, whole grains

29 Gardner, Ann Intern Med, 2005 EFFECT OF PLANT-BASED DIET LDL mg/dl Low fat-7.0 Low fat plus-13.8 Conclusion: current guidelines may underestimate potential LDL-lowering effect

30 Jenkins, Am J Clin Nutr, 2005 Cholesterol-Lowering Foods vs Lovastatin 46 volunteers with hyperlipidemia, 1 month study, foods provided Randomized to control diet vs control diet and lovastatin vs dietary portfolio Control diet: vegetarian, very low in saturated fat, whole wheat cereals, low fat dairy foods Portfolio diet: also very low saturated fat, vegetarian diet, plus high in plant sterols, soy protein, soluble fibers, almonds

31 Jenkins, Am J Clin Nutr, 2005 DIETARY PORTFOLIO Breakfast: Oat bran cereal, soy beverage, strawberries, sugar and psyllium, oat bran bread, enriched margarine (with sterols), fruit jam Snack: Almonds, soy beverage, fresh fruit Lunch: Black bean soup, sandwich (soy deli slices, oat bran bread, enriched margarine, lettuce, tomato, cucumber) Snack: Almonds, psyllium, fresh fruit Dinner: Tofu bake with ratatouille (tofu, eggplant, onions, peppers) Snack: Fresh fruit, psyllium, soy beverage

32 Jenkins, Am J Clin Nutr, 2005 Cholesterol-Lowering Foods vs Lovastatin LDL CRP Control -8.0%-10.0% Control/statin -30.9% -33.3% Portfolio -28.6% -28.2%

33 Case 4 50 year old woman, in good health, in for check up. BMI 32 with metabolic syndrome. She says, I have to lose weight, and I am planning on doing that. I am about to try the South Beach diet.

34 Dansinger, JAMA 2005 COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE Intention to treat at 1 year Atkins Ornish WWZone Wt Loss (kg) 2.1 3.33.0 3.2 Completers (%) 53 5065 65 Completers at 1 year Atkins Ornish WWZone Wt Loss (kg) 3.9 6.64.6 4.9 160 patients, randomly assigned

35 Dansinger, JAMA, 2005 COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE { "@context": "http://schema.org", "@type": "ImageObject", "contentUrl": "http://images.slideplayer.com/258015/1/slides/slide_34.jpg", "name": "Dansinger, JAMA, 2005 COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE

36 Dietary Guidelines for Americans, 2005 2005 Dietary Guidelines Adequate nutrients within calorie needs: limit saturated and trans fats, cholesterol, added sugars, salt and alcohol Weight management: balance intake and output Physical activity: to reduce risk of disease: 30 min moderate intensity most days to prevent weight gain: 60 minutes to sustain weight loss: 60-90 minutes Food groups encouraged: 2 cups of fruit/day 2.5 cups vegetables/day 3 servings whole grains 3 servings low-fat dairy


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