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).