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Dr. Tony Cohn
Centre for Addiction and Mental Health
A Nutraceutical Approach
to Metabolic Management
Nutraceutical
Nutrition + Pharmaceutical
“ A foodstuff that is held to provide health or
medical benefits in addition to it’s basic
nutritional value”
Dietary supplements and “functional food”
“ Let food be thy medicine and medicine thy food”
Hippocrates 460 BC
Outline
• Metabolic Syndrome & Metabolic Dyslipidemia
with focus on Early Psychosis
• How is Metabolic Syndrome Managed ?
• Nutrition A. Diet in General
B. Nutraceutical (Niacin and Omega 3)
Metabolic Syndrome
• 1983 - Wingard D.L. et al (Am J Epidemiol 117; 19-26) investigated a clustering of heart disease risk factors
• 1988 - The first referral of the syndrome was described by Reaven, G.M as Syndrome X (Diabetes 1988)
• Also referred to as:
• The Deadly Quartet (Kaplan, NM Arch Int Med 1989)
• Insulin Resistance Syndrome (DeFronzo et al Diabetes Care 1991)
• Plurimetabolic Syndrome (Caro JF J Clin Endocrinol Metab 1991)
Insulin Resistance/ Glucose
intolerance
Abdominal obesity
Hypertension
Atherogenic dyslipidemia
Proinflammatory/
Prothrombotic state
Characteristics of the Metabolic Syndrome: NCEP-
ATP III
National Cholesterol Educational Program (NCEP), Adult Treatment Panel (ATP) III; 2001.
Diabetes CVD
Clinical Definitions of the Metabolic Syndrome
Confirmed Type 2
diabetes,IFG, IGT or
insulin resistance plus
any 2 of the following
risk factors
Insulin resistance
(FI top 25%)
plus any 2 of the
following risk factors
Any 3 of the
following risk
factors
IGT or IFG
plus any of the
following
Waist girth* plus any
other 2 of the 4 risk
factors
Obesity BMI > 30 kg/m2 or
Waist:Hip ratio > 0.9 M
> 0.85 F
WC: M > 94 cm
F > 80 cm
WC: M > 102 cm
F > 88 cm
BMI > 25 kg/m2 Europid M > 94 cm
Europid F > 80 cm
(ethnic specific values
for other groups)
Triglycerides > 1.7 mmol/L > 2.0 mmol/L > 1.7 mmol/L
> 1.7 mmol/L > 1.7 mmol/L (or lipid
treatment )
HDL-C < 0.9 mmol/L M,
< 1.0 mmol/L F
< 1.0 mmol/L M &
F
< 1.0 mmol/L M,
< 1.3 mmol/L F
< 1.0 mmol/L M,
< 1.3 mmol/L F
< 0.9 mmol/L (or
specific lipid treatment)
B P > 140/90 mm Hg > 140/90 mm Hg
and/or medication
> 130 /85 mm Hg > 130 /85 mm Hg > 130 /85 mm Hg
Fasting
Glucose
Included above > 6.1-6.9 mmol/L > 6.1 mmol/L
IFG or IGT (but not
diabetes)
> 5.6 mmol/L
or previously T2DM
Other Microalbuminuria
2Hr PG 7.8-
11mmol/L
Other features of
insulin resistance
WHO
1999
European Group for the
Study of Insulin Resistance
(EGIR) 1999 NCEP, ATP III
2001
IDF
2005
Grundy et al 2005 Circulation 112
AACE
2003
2005 AHA/ NHLBI criteria for clinical diagnosis of the
metabolic syndrome = 3 of the following:
Risk Factor Level
Abdominal Obesity * (Waist circumference)
Men: > 102 cms (40 in)
Women: > 88 cms (35 in)
Hypertriglyceridemia Fasting triglycerides > 1.69 mmol/L /or meds
Low HDL Cholesterol Men: < 1.04 mmol/L
Women: < 1.29 mmol/L/or meds
High blood pressure 130/85 or on antihypertensive medication
High fasting glucose 5.6 mmol/L or on antidiabetic medication
*
•Lower thresholds are appropriate for Asian Americans (e.g. 90 cm men; 80cm women)
•Some non Asians may also develop MS at lower WC thresholds
Grundy et al 2005 Circulation 112
Metabolic Syndrome Prevalence in Canada
0
5
10
15
20
25
30
35
40
45
Native Indians South Asians Europeans Chinese
Anand, S. et al Circulation 2003; 108:420-425
% Prevalence
Amongst Various
Ethnic Groups in
Canada
ATP III definition
Canadian Adult population - 25.8%
(95% CI, 23.5 to 28.2)
41.6
25.9
22
11
N = 1276 (51% F)
P = 0.0001
1470 Patients with Schizophrenia
Screened over 4 years
Caucasian African South Asian
N 1038 268 164
Mean Age 41 ± 14 36 ± 13 36 ± 12
Diabetic
10.5 % 18.5% 20.6 %
Cohn, T. 2012 Unpublished
South Asian Patients with Schizophrenia
Cigarette
Smokers
56 (35%)
Non
Smokers
108
P
Diabetic 36% 13% 0.001
Cohn, T. 2012 Unpublished
Peel: Population Demographic and Metabolic Vulnerability
REGION OF
PEEL
2001 2006 % Change
Total Population 985,565 1,154,070 17.1
Non-Visible
Minority
Population
606,460 577,400 -4.8
Visible Minority
Population
379,105 576,665 52.1%
South Asian 155,050 272,760 75.9 %
Black 70,695 95,565 35.2 %
Source: Statistics Canada, Census of Canada, 2001; 2006.
Note: All percentages are calculated using total population as the denominator.
Rates of the Metabolic Syndrome in Patients with
Chronic Schizophrenia (ATP III definition)
42.6
48.5
23.424
0
10
20
30
40
50
60
Males Females
Subjects
US Adult
%
Cohn, Remington et.al. Can. J. Psychiatry November 2004
P < 0.0001 P < 0.0001
Rates of the Metabolic Syndrome and Age
43.5
6.7
0
10
20
30
40
50
60
Age 20-29 Age 60-69
Combined
40.743.1
5045.9
0
10
20
30
40
50
60
Age <45 Age 45+
Males
Females
US Adult Population NHANS III
Schizophrenia Sample
% %
Metabolic Syndrome Rates (ATP III) in Patients on SGA
Medications (N= 9,450) versus General Population
%
Pilot Data, Cohn T. Unpublished
Met.Syndrome Rates (ATP III) by Gender in Pts. on SGA
Medications (N= 9,450) versus General Population
Pilot Data, Cohn T. Unpublished
Patients Treated on SGA Medication age 20-29
N 1042 ( 72% male)
Age (yr) 25 ± 3
Metabolic Syndrome (ATP III) 23% (General Pop rate 6.7%)
Hyperinsulinemia (F. Insulin > 60 pMol/L) 36% (African and Hispanic)
Metabolic Dyslipidemia (Triglycerides) 27% (Caucasian)
Metabolic Dyslipidemia (HDL) 43% (African and Caucasian)
Abdominal Adiposity 41% (Hisp. and Caucasian)
BP 33% (African)
Increased Glucose 9%
Pilot Data, Cohn T. Unpublished
Interventions for Metabolic Syndrome
• DYSLIPIDEMIA
• DYSGLYCEMIA
• HYPERTENSION
MEDICATION/
NUTRACEUTICAL EXERCISE
DIET
QUALITY WEIGHT LOSS
How our patients eat (N=103)
Male (61) Female (42)
Kilocalories 2094 (2,478)* 1776 (1,732)
% Kcal Carbohydrate
56% (48%)* 55% (50%)*
% Kcal Fat 29% (35)* 30% (35)*
% Kcal Protein 16% (15%) 16% (15%)
• High refined CHO, especially in the form of high fructose corn syrup
• Decrease fiber
• Saturated and trans fat from processed food
Cohn T. Unpublished
Canada’s Food Guide
Recommended
Daily Servings by
Food Group
In Patients
(27)
Out Patients
With meals
provided(13)
Outpatients
Without meals
Provided (28)
Grains 5-12 5.5 7.1 6.7
Fruit/Veg 5-10 5.6 5.7 5.4
Milk 2-4 2.1 2.3 1.8
Meat or
Substitutes
2-3 2.3 2.3 2.1
Other Moderation 8 11.4 15.8
Cohn T. Unpublished
Folate Levels
23.2
35.79
0
5
10
15
20
25
30
35
40
Psych Patients Gen.Hosp Controls
Serum FolateN=811
N=70
P .000483
nmol/L
Koren G, Cohn T. Am. J. Psychiatry. 2002
Dietary treatment of the metabolic syndrome:
What is The Optimum Diet?
Targets: To improve insulin sensitivity and to correct/prevent associated metabolic/CV abnormalities
Weight reduction (diet and exercise)
5 -10% body weight loss can result in 30 - 60% improvement in insulin sensitivity
(Riccardi G, Rivellese AA. Br J Nutr 2000;83 Suppl 1:S143-A148)
.
Dietary treatment of the metabolic syndrome:
What is The Optimum Diet?
Diet quality
• Lower total Fat < 30%, saturated fat < 10%
• Increase MUFA
• CHO: focus on Low GI, increased fruits, vegetables, legumes, whole grains, fibre (viscous fibres)
• Increase protein (nuts, seeds, soy)
• Decrease sodium (<2400mg/day)
• Moderate alcohol consumption
(Riccardi G, Rivellese AA. Br J Nutr 2000;83 Suppl 1:S143-A148)
Traffic Light Diet:
•
For each food group, try to choose food from “Green” and “Yellow” column to ensure that
you get food that helps to reduce your metabolic risks.
Choose most often Choose more often Choose less often
Milk Products:
Skim milk 1%, 2% Whole milk
Diet yogurt or low fat yogurt Regular yogurt
Processed cheese (<7% M.F.)
Low fat cheese (<20% M.F) Regular Cheese
Meat and Alternatives
Fish (salmon, tuna) Egg Beef
Chicken Lean meat Pork
Legumes (Lentils, chickpeas, etc) Low fat peanut butter
Tofu
Nutraceutical Management of Antipsychotic Associated Metabolic Dyslipidemia
• Niacin (B3) lowers trigs, LDL; increases HDL1
• Niaspan covered under Ontario Drug Benefit
• Omega-3 FA improves CV risk profile in MS2
• 2-3 gm EPA plus DHA lowers Trigs by 25-30%3
• Niacin plus Omega -3 FA effective4
• ? Antipsychotic metabolic dyslipidemia
1Brown et al N Engl J Med 323(19) 1990; Canner et al. Am J Cardiol 97 2006 2Ebrahimi et al. Acta Cardiol 64 2009;
3 American Heart Association ; 4 Isley et al Journal of Clinical Lipidology 1 2007
Niacin for Antipsychotic Metabolic Dyslipidemia
N 9 ( 8 males)
Age (yr) 33 ± 7
Diagnosis Schizophrenia (8); Schizoaffectve (1)
Antipsychotic Clozapine (7); Olanzapine (2)
Niaspan FCT 2000mg for 7 ± 2 mths
Baseline End
Mean
(mmol/L)
MS Criteria
(%)
MS Criteria
(%)
Change Mean
%
p
Fasting
Triglycerides
3.1 ± 0.83 100% 56% - 1.17 ± 0.9
- 38%
.005
Fasting
HDL Chol.
0.86 ± 0.19 100% 44% + .35 ± 0.27
+ 85%
.005
Pilot Data, Cohn T. Unpublished
Case Example
• 32 YO Single man
• Diagnosis: Schizophrenia
• Gained ~ 60LB on risperidone; BMI 35; F. Trig 4.18; HDL 0.92
• Decompensated and hospitalized; clozapine initiated
• Jan 2011- BMI down to 30
• Metabolic Dyslipidemia
• Niaspan Initiated
12/01/11
WC 118
F. Trig 2.53
F. HDL 0.84
F. Gluc 5.5
BP 140/90
MS Criteria 4/5
Pilot Data, Cohn T. Unpublished
Niaspan Plus Omega-3 for Metabolic Dyslipidemia
Single Case: 38 YO Man; Schizophrenia; Clozapine 450mg
Niaspan
Cohn T. Unpublished Pilot data
1.69
1.04
Summary
• The metabolic syndrome (MS) is a constellation of risk factors that increase the risk of CHD and type 2 diabetes
• MS is not a discrete entity and shows variation in its components1
• MS best captures the metabolic features of patients treated for psychosis and development of MS is accelerated in those with early psychosis
• Lifestyle intervention should precede and should be used in combination with drug therapies2
• Dietary intervention is focussed on weight loss and diet quality is geared to the address individual MS components3
• Niacin and Omega 3 are effective interventions for antipsychotic associated metabolic dyslipidemia that warrant further study
2Grundy et al 2005 Circulation 112 3Riccardi, G 2000 Brit,J Nutrition 83
1Shen BJ et al. Am J Epidemiol 2003;157(8).