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

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

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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

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All Participants

Howard, B. V. et al. JAMA 2006;295:39-49.

LOW-FAT DIET AND WEIGHT CHANGE

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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