Transcript CURRENT ISSUES IN CLINICAL NUTRITION

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
Selected Topics
 Vitamin, mineral and fish oil supplements

Low-fat diets

Diet and lipid disorders

Diet, exercise and weight loss
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?
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.
Placebo
199
Hazard Ratio
0.88 (0.72-1.08)
181
197
0.90 (0.74-1.10)
Arm/wrist 565
557
1.01 (0.90-1.14)
Total
2158
0.96 (0.91-1.02)
Hip
Calcium/D
175
Vertebral
2102
Jackson, 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
Cancer
168
Placebo
154
Hazard Ratio
1.08 (0.86-1.34)
Wactawski-Wende, 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
Year 1
Comparison
Year 1
Difference Between Groups
Year 3
Year 6
Fat
24.3%
35.1%
-9.5%
-8.1%
Calories
1500 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
BREAST CANCER
(Cases, annualized per cent)
Intervention
Comparison
HR
p
Breast Cancer
Incidence
Mortality
0.42
0.02
0.45
0.02
0.91 (0.83-1.01)
0.77 (0.48-1.22)
.09
.27
Total Cancer
Incidence
Mortality
1.23
0.28
1.28
0.29
0.96 (0.91-1.02)
0.95 (0.84-1.07
.10
.22
0.60
0.61
Total mortality
0.98 (0.91-1.07)
Prentice, NEJM 2006
.29
LOW-FAT DIET AND INVASIVE COLON CANCER
Time, y
Beresford, S. A. A. et al. JAMA 2006;295:643-654.
LOW-FAT DIET AND CARDIOVASCULAR DISEASE
All Participants
Time, y
Participants Without a
History of CVD
Time, y
Howard, B. V. et al. JAMA 2006;295:655-666.
LOW-FAT DIET AND WEIGHT CHANGE
Overall
Howard, B. V. et al. JAMA 2006;295:39-49.
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.
VITAMIN E AND CARDIOVASCULAR
DISEASE
Vitamin E vs placebo
7 RCTs; 106,625 subjects
Vit E
Placebo
CV event
4832
CV death
2683
MI
1255
Stroke
742
4895
2689
1254
723
NS
NS
NS
NS
Eidelman, JAMA, 2004
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
Cancer
552
Cancer deaths 156
CV events
1022
Heart failure
Hosp for CHF
641
236
Placebo
586
178
985
p
.30
.24
.34
578
196
.03
.045
Hope and Hope-TOO Investigators,
JAMA, 2005
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
CV event
482
MI
196
Stroke
241
CV deaths
106
Placebo
517
195
246
140
p
0.26
0.96
0.82
0.03
Invasive cancer
1437
1428
0.87
Total mortality
636
615
0.53
Lee, JAMA, 2006
Beta-CAROTENE AND
CARDIOVASCULAR DISEASE
Beta-carotene vs placebo
8 RCTs; 138,113 subjects
Mortality
Carotene 7.3%
Placebo
NNH*
CV death
3.3%
Stroke
2.4%
7.0%
3.1%
2.3%
326
409
NS
* number needed to harm
Vivekananthan, Lancet, 2003
FOLATE AND RESTENOSIS AFTER
STENTING
636 patients, post stent
Randomized to folic acid, B6 and B12
vs placebo, 6 month f/u
B vitamins
Placebo
Restenosis
35.5%
Lumen
1.59mm
Revasc
15.8%
26.5%
1.74mm
10.6%
p=0.05
p=0.008
p=0.05
Lange, NEJM, 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
Low dose
Stroke
148
CHD
123
Death
117
High dose
152
114
99
p=0.80
p=0.57
Combined
316
p=0.25
Toole, JAMA, 2004
303
p=0.61
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
1.22
p
0.05
MI
1.23
0.06
Stroke
0.83
0.52
Cancer
1.02
0.94
Total mortality
1.21
0.19
Combined events
Bonaa, 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
0.95
0.41
CV Death
0.96
0.59
MI
0.98
0.82
Stroke
0.75
0.03
0.99
0.94
Combined events
Total mortality
HOPE 2, NEJM, 2006
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
Time to First Episode of ICD Therapy by
Fish Oil vs Placebo Group
Raitt, JAMA 2005
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
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
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. LDLcholesterol 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
Patients with 0–1 Risk Factor
2001 and 2004
LDL Level at Which to
Initiate Diet
LDL Goal
<160 mg/dL
160 mg/dL
LDL Level at Which to
Consider Drug Therapy
190 mg/dL
(160–189 mg/dL:
LDL-lowering drug
optional)
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
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)
Total
–16
–36 mg/dl
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
Gardner, Ann Intern Med, 2005
EFFECT OF PLANT-BASED DIET
LDL mg/dl
Low fat
Low fat plus
-7.0
-13.8
Conclusion: current guidelines may
underestimate potential LDL-lowering effect
Gardner, Ann Intern Med, 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
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
Jenkins, Am J Clin Nutr, 2005
Cholesterol-Lowering Foods vs
Lovastatin
Control
LDL
-8.0%
CRP
-10.0%
Control/statin
-30.9%
-33.3%
Portfolio
-28.6%
-28.2%
Jenkins, Am J Clin Nutr, 2005
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.”
COMPARISON OF ATKINS, ORNISH,
WEIGHT WATCHERS, AND ZONE
160 patients, randomly assigned
Intention to treat at 1 year
Wt Loss (kg)
Completers (%)
Atkins
2.1
53
Ornish
3.3
50
WW
3.0
65
Zone
3.2
65
Ornish
6.6
WW
4.6
Zone
4.9
Completers at 1 year
Wt Loss (kg)
Atkins
3.9
Dansinger, JAMA 2005
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
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
Dietary Guidelines for Americans,
2005