current issues in clinical nutrition robert b. baron md ms professor and associate dean ucsf school...
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CURRENT ISSUES IN CLINICAL CURRENT ISSUES IN CLINICAL NUTRITIONNUTRITION
Robert B. Baron MD MSRobert B. Baron MD MS
Professor and Associate Dean Professor and Associate Dean
UCSF School of MedicineUCSF School of Medicine
Declaration of full disclosure: No conflict of interest
Selected TopicsSelected Topics
Vitamin, mineral and fish oil supplements
Low-fat diets
Diet and lipid disorders
Diet, exercise and weight loss
Case 1Case 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?
Jackson, NEJM 2006
CALCIUM, VITAMIN D AND CALCIUM, VITAMIN D AND FRACTURESFRACTURES
36,282 postmenopausal women, 50-79Randomized to 1000 mg calcium plus 400 IU of
vitamin D vs placebo, 7 year f/u.
Calcium/D Placebo Hazard Ratio Hip 175 199 0.88 (0.72-1.08)
Vertebral 181 197 0.90 (0.74-1.10)
Arm/wrist 565 557 1.01 (0.90-1.14)
Total 2102 2158 0.96 (0.91-1.02)
Wactawski-Wende, NEJM 2006
CALCIUM, VITAMIN D AND INVASIVE CALCIUM, VITAMIN D AND INVASIVE COLON CANCERCOLON CANCER
36,282 postmenopausal women, 50-79Randomized to 1000 mg calcium plus 400 IU of
vitamin D vs placebo, 7 year f/u.
Calcium/D Placebo Hazard Ratio Cancer 168 154 1.08 (0.86-1.34)
Prentice, NEJM 2006
LOW-FAT DIET AND INVASIVE LOW-FAT DIET AND INVASIVE BREAST CANCERBREAST 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 1 Year 1 Year 3 Year 6
Fat 24.3% 35.1% -9.5% -8.1%
Calories1500 kcals 1594 kcals -93 -119.9
F and V 5.1 servings 3.9 servings +1.3 +1.1
Weight 74.4 kg 76.3 kg -1.3kg -0.8kg
Prentice, NEJM 2006
LOW-FAT DIET AND INVASIVE LOW-FAT DIET AND INVASIVE BREAST CANCERBREAST CANCER
(Cases, annualized per cent) Intervention Comparison HR p
Breast Cancer Incidence 0.42 0.45 0.91 (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
Cu
mm
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tive
Haz
ard
Time, y
LOW-FAT DIET AND INVASIVE COLON CANCER
Beresford, S. A. A. et al. JAMA 2006;295:643-654.
Howard, B. V. et al. JAMA 2006;295:655-666.
LOW-FAT DIET AND CARDIOVASCULAR DISEASE
Time, y
Cu
mm
ula
tiv
e H
aza
rd
Time, y
Cu
mm
ula
tiv
e H
aza
rd Participants Without a History of CVD
All Participants
Howard, B. V. et al. JAMA 2006;295:39-49.
LOW-FAT DIET AND WEIGHT CHANGE
Mea
n D
iffe
ren
ce,
kgOverall
Case 2Case 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.
Eidelman, JAMA, 2004
VITAMIN E AND CARDIOVASCULAR VITAMIN E AND CARDIOVASCULAR DISEASEDISEASE
Vitamin E vs placebo
7 RCTs; 106,625 subjects
CV event CV death MI StrokeVit E 4832 2683 1255 742
Placebo 4895 2689 1254 723
NS NS NS NS
Hope and Hope-TOO Investigators, JAMA, 2005
VITAMIN E, CARDIOVASCULAR VITAMIN E, CARDIOVASCULAR EVENTS AND CANCER: HOPE TOOEVENTS 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 pCancer 552 586 .30Cancer deaths 156 178 .24CV events 1022 985 .34
Heart failure 641 578 .03Hosp for CHF 236 196 .045
Lee, JAMA, 2006
VITAMIN E AND CARDIOVASCULAR VITAMIN E AND CARDIOVASCULAR DISEASE AND CANCERDISEASE AND CANCER
Women’s Health Study, Vitamin E 600 IU QOD vs placebo39,876 subjects, over 45 years old, 10.1 yrs f/u
Vitamin E Placebo pCV event 482 517 0.26
MI 196 195 0.96Stroke 241 246 0.82CV deaths 106 140 0.03
Invasive cancer 1437 1428 0.87
Total mortality 636 615 0.53
Vivekananthan, Lancet, 2003
BetaBeta-CAROTENE AND -CAROTENE AND CARDIOVASCULAR DISEASECARDIOVASCULAR DISEASE
Beta-carotene vs placebo 8 RCTs; 138,113 subjects
Mortality CV death Stroke Carotene 7.3% 3.3% 2.4%
Placebo 7.0% 3.1% 2.3%
NNH* 326 409 NS
* number needed to harm
Lange, NEJM, 2004
FOLATE AND RESTENOSIS AFTER FOLATE AND RESTENOSIS AFTER STENTINGSTENTING
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
Toole, JAMA, 2004
VITAMIN INTERVENTION FOR VITAMIN INTERVENTION FOR STROKE PREVENTION (VISP)STROKE PREVENTION (VISP)
3680 adults, s/p strokeRandomized to:
Mulitivit with low dose B6, B12, folic acid Multivit with high dose B6, B12, folic acid
Stroke CHD Death Combined Low dose 148 123 117 316
High dose 152 114 99 303
p=0.80 p=0.57 p=0.25 p=0.61
Bonaa, NEJM, 2006
HOMOCYSTEINE LOWERING AND HOMOCYSTEINE LOWERING AND CARDIOVASCULAR EVENTS (NORVIT)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 pCombined events 1.22 0.05
MI 1.23 0.06
Stroke 0.83 0.52
Cancer 1.02 0.94
Total mortality 1.21 0.19
HOPE 2, NEJM, 2006
HOMOCYSTEINE LOWERING AND HOMOCYSTEINE LOWERING AND CARDIOVASCULAR EVENTS (HOPE 2)CARDIOVASCULAR EVENTS (HOPE 2)
5522 men and women with vascular disease or diabetes 55 and older; 5 year f/uFolic 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 0.96 0.59
MI 0.98 0.82
Stroke 0.75 0.03
Total mortality 0.99 0.94
Raitt, JAMA, 2005
FISH OIL AND SUDDEN DEATHFISH 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
Raitt, JAMA 2005
Time to First Episode of ICD Therapy by Fish Oil vs Placebo Group
MacLean, JAMA, 2006
OMEGA-3 FATTY ACIDS AND CANCEROMEGA-3 FATTY ACIDS AND CANCER
Systematic review of 38 studies
20 cohorts, 11 types of cancers:Breast: 1 increased, 3 decreased, 7 no associationColon: 1 decreased, 17 no associationLung: 1 increased, I decreased, 4 no associationProstate: 1 decreased, 15 no associationSkin: 1 increasedAerodigestive, bladder, lymphoma, ovarian, pacreatic, and stomach: no association
Case 2Case 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
Case 3Case 353 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?
LDL Goal and Cutpoints LDL Goal and Cutpoints Patients with 0–1 Risk FactorPatients with 0–1 Risk Factor
2001 2001 andand 2004 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 DietLDL Goal
ATP III, NCEP 2001
Therapeutic Lifestyle Changes (TLC): Therapeutic Lifestyle Changes (TLC): Major featuresMajor 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
TLC for patients with LDL-C = 160
Dietary ComponentDietary Component LDL-C LDL-C (mg/dL) (mg/dL)
Low saturated fat/dietary Low saturated fat/dietary cholesterolcholesterol ––1212
Viscous fiber (10–25 g/d)Viscous fiber (10–25 g/d) – –88
Plant stanols/sterols (2 g/d)Plant stanols/sterols (2 g/d) ––1616
TotalTotal – –36 mg/dl36 mg/dl
Gardner, Ann Intern Med, 2005
EFFECT OF A PLANT-BASED DIETEFFECT 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
Gardner, Ann Intern Med, 2005
EFFECT OF PLANT-BASED DIETEFFECT 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
Jenkins, Am J Clin Nutr, 2005
Cholesterol-Lowering Foods vs Cholesterol-Lowering Foods vs Lovastatin 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
Jenkins, Am J Clin Nutr, 2005
DIETARY PORTFOLIODIETARY PORTFOLIOBreakfast: 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
Jenkins, Am J Clin Nutr, 2005
Cholesterol-Lowering Foods vs Cholesterol-Lowering Foods vs Lovastatin Lovastatin
LDL CRPControl -8.0% -10.0%
Control/statin -30.9% -33.3%
Portfolio -28.6% -28.2%
Case 4Case 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.”
Dansinger, JAMA 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE
Intention to treat at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 2.1 3.3 3.0 3.2Completers (%) 53 50 65 65
Completers at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 3.9 6.6 4.6 4.9
160 patients, randomly assigned
Dansinger, JAMA, 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE
Each group: 25% lost 5%, 10% lost 10% of initial weight
Each diet reduced LDL/HDL by 10%
No significant effects on BP or glucose
Weight loss associated with adherence, but not diet type
CRP and insulin reductions associated with weight loss, but not diet
Dietary Guidelines for Americans, 2005
2005 Dietary Guidelines2005 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