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. Vitamin, mineral and fish oil supplements
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. 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
Hip ( )
Vertebral ( )
Arm/wrist ( )
Total ( )
Jackson, NEJM 2006

5. 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
Cancer ( )
Wactawski-Wende, NEJM 2006

6. 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 1 Year Year Year 6
Fat 24.3% % % %
Calories 1500 kcals kcals
F and V 5.1 servings servings
Weight kg kg -1.3kg kg
Prentice, NEJM 2006

7. LOW-FAT DIET AND INVASIVE BREAST CANCER
(Cases, annualized per cent)
Intervention Comparison HR p
Breast Cancer
Incidence ( )
Mortality ( )
Total Cancer
Incidence ( ) .10
Mortality (
Total mortality ( )
Prentice, NEJM 2006

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

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

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

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. VITAMIN E AND CARDIOVASCULAR DISEASE
Vitamin E vs placebo
7 RCTs; 106,625 subjects
CV event CV death MI Stroke
Vit E
Placebo
NS NS NS NS
Eidelman, JAMA, 2004

13. 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
Cancer
Cancer deaths
CV events
Heart failure
Hosp for CHF
Hope and Hope-TOO Investigators, JAMA, 2005

14. VITAMIN E AND CARDIOVASCULAR DISEASE AND CANCER
Women’s 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 event MI
Stroke
CV deaths
Invasive cancer
Total mortality
Lee, JAMA, 2006

15. Beta-CAROTENE AND CARDIOVASCULAR DISEASE
Beta-carotene vs placebo
8 RCTs; 138,113 subjects
Mortality CV death Stroke
Carotene % % 2.4%
Placebo % % 2.3%
NNH* NS
* number needed to harm
Vivekananthan, Lancet, 2003

16. 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 % mm 15.8%
Placebo % mm 10.6%
p= p= p=0.05
Lange, NEJM, 2004

17. 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 Death Combined
Low dose
High dose
p= p= p= p=0.61
Toole, JAMA, 2004

18. 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 events MI
Stroke
Cancer
Total mortality
Bonaa, NEJM, 2006

19. 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
CV Death MI
Stroke
Total mortality
HOPE 2, NEJM, 2006

20. 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
Raitt, JAMA, 2005

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

22. 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
MacLean, JAMA, 2006

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 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. 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
ATP III, NCEP 2001

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
Plant stanols/sterols (2 g/d)
–16
Total
–36 mg/dl
Dietary adjuncts
This slide shows that in a hypothetical patient with an LDL-C of 160 mg/dL, average reductions in LDL-C obtained by a diet lower in saturated fat and dietary cholesterol and the addition of viscous fiber and plant stanol/sterol esters could reduce LDL-C to <130 mg/dL. This is the goal for many patients with multiple risk factors and may obviate the need for cholesterol-lowering drug therapy or an increase in dosage of cholesterol-lowering drug therapy.
References:
Walden CE, Retzlaff BM, Buck BL, McCann BS, Knopp RH. Lipoprotein lipid response to the National Cholesterol Education Program Step II diet by hypercholesterolemic and combined hyperlipidemic women and men. Arterioscler Thromb Vasc Biol 1997;17:
Jenkins DJ, Kendall CW, Axelsen M, Augustin LS, Vuksan V. Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease. Curr Opin Lipidol 2000;11:49-56.
Cato N. Stanol meta-analysis. Personal communication, 2000.

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

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

30. 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
Jenkins, Am J Clin Nutr, 2005

31. 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
Jenkins, Am J Clin Nutr, 2005

32. Cholesterol-Lowering Foods vs Lovastatin
LDL CRP
Control % -10.0%
Control/statin % %
Portfolio % %
Jenkins, Am J Clin Nutr, 2005

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. COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE
160 patients, randomly assigned
Intention to treat at 1 year
Atkins Ornish WW Zone
Wt Loss (kg)
Completers (%)
Completers at 1 year
Wt Loss (kg)
Dansinger, JAMA 2005

35. COMPARISON OF ATKINS, ORNISH, WEIGHT 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
Dansinger, JAMA, 2005

36. Dietary Guidelines for Americans, 2005
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: minutes
Food groups encouraged:
2 cups of fruit/day
2.5 cups vegetables/day
3 servings whole grains
3 servings low-fat dairy
Dietary Guidelines for Americans, 2005