MICRONUTRIENTS FOR THE BRAIN

Bonnie J. Kaplan, PhDProfessor EmeritaCumming School of MedicineUniversity of Calgary

Calgary Neuropathy AssociationJanuary 17, 2018

Disclosure

No commercial interest in any company or sale of any product

Disclaimer

The relevance of this research to neuropathy is not at all clear to me!

NUTRITION: THERE ARE 2 SIDES TO THIS

WHAT WE EAT THAT MAYBEWE SHOULD NOT EAT

Casein/dairy

Artificial additives

Gluten

WHAT WE SHOULD EAT BUT MAY NOT BE GETTING ENOUGH OF

Vitamins

Omega-3 fatty acids

Minerals

OVERVIEW

1. Why pay attention to mental health in general? (because it is not this group’s focus)

2. Why pay attention to nutrition in relation to brain/mental health?

3. What types of data confirm the importance of nutrition to mental health?

4. Societal issues

1. WHY PAY ATTENTION TO MENTAL HEALTH IN GENERAL?

Because we have a problem of epidemic proportions

THE INVISIBLE PLAGUE: THE RISE OF MENTAL ILLNESS FROM 1750 TO THE PRESENT (2001)E. FULLER TORREY & JUDY MILLER

Ø Excellent data 1750 – 1960 from England and Wales, Ireland, Canadian Atlantic provinces, and the USA

Ø Very concerned because amount of ‘insanity’ seemed to be increasing, to 0.03% in 1960

0

2

4

6

8

10

12

14

16

18

20

Prior to 1750

1750-1960 Irish famine

Prevalence

.01 .03 .07

Prev

alen

ce o

f dia

gnos

ed m

enta

l illn

ess

in %

0

2

4

6

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Prior to 1750

1750-1960 Irish famine Now

Prevalence

.01 .03 .07

Over 20%Pr

eval

ence

of d

iagn

osed

men

tal i

llnes

s in

%

TAKE HOME MESSAGE

• We have a problem of epidemic proportions

• Conventional treatments are not helping much

2. WHY PAY ATTENTION TO NUTRITION IN RELATION TO MENTAL HEALTH?

Brain health is probably more dependent on optimal nutrition than any other organ

*

Our brain

accounts for ≈ 2% of our body weight

but,

it represents20-50% of our

metabolicdemands

Ø Each of us has ~6 liters of blood inside us

Ø ~1 liter passes through our brain every minute

WHAT IS THAT BLOOD DOING?✔ Nutrients

✔ Oxygen

✔ Other immunulogic factors your brain needs✔ Remove waste products

BRAIN METABOLISM

Why so many nutrients every minute?

ONE SMALL PORTION OF SEROTONIN PATHWAY

6-Hydroxy-kynurenate

5-Hydroxy-N-formylkyunrenine

5-Hydroxyindole-acetyaldehyde

5-Hydroxy-L-tryptophan

5-Hydroxy-indolepyruvate Serotonin

3-Formyl-aminobenzaldehyde

Indole

Tryptophan

3-Indole-glycolaldehyde

Vit. B6

Vit. B6

Vit. B6

Vit. B6

Copper

IronMolybdenum

Copper

Iron

25% of calories from junk food

⍺-Linolenic Acid (ALA)

Stearidonic Acid

Eicosatetraenoic Acid

Eicosapentaenoic Acid (EPA)

DocosapentaenoicAcid (DPA)

Docosahexaenoic Acid (DHA)

Linoleic Acid (LA)

y-Linoleic Acid (GLA)

Dihomo y-Linoleic Acid (DGLA)

Arachidonic Acid (AA)

Corn, Soybean, Sunflower,

Safflower Oils

Evening Primrose,Borage Oil

Meat, Eggs,Dairy

Flax, Soybean, Canola Oils,

Walnuts

Hemp & Modified Veg. Oils

Fish, Fish/Krill Oil,Seaweed

Fish, Fish/Krill Oil, Algae

OMEGA-3 OMEGA-6

<----------------Δ6-desaturase-------------->

<------------------Elongase----------------->

<-------------------- Δ5-desaturase------------>

Elongase

24:5n-3

24:6n-3

Δ6-desaturase

β-oxidation

(Cofactors: Vit C, B3, B6, Mg, Zn)

(Cofactor: B6)

(Cofactors: Vit C, B3, Zn)

(Cofactors: VitC, B3, B6, Mg, Zn)

(Cofactor: B6)Elongase(Cofactor: B6)

TAKE HOME MESSAGE

We eat for our brainsOptimal brain function requires a broad spectrum of minerals and vitamins for metabolism

3. WHAT TYPES OF DATA CONFIRM THE IMPORTANCE OF NUTRITION TO MENTAL HEALTH?

correlationalprospectivetreatment

~15 POPULATION HEALTH STUDIES:MEDITERRANEAN VS WESTERN DIET

Mediterranean, whole foods diet associated withlower rates of mood and anxiety symptoms

Western, processed foods diet associated withhigher rates of mood and anxiety symptoms

Jacka et al., PLoS ONE, 2011Sanchez-Villegas et al., Public Health and Nutrition, 2012

Liu et al., Am J Clin Nutr, 2002Jacka et al, Am J Psychiatry, 2010

Chrysohoou et al. J Am Coll Cardiol, 2004.

THE PROBLEM WITHCORRELATIONAL DATA

DIET HIGH IN PROCESSED FOOD

MOOD, ANXIETYSYMPTOMS

TO PROVE CAUSALITY

1. Prospective, longitudinal studies (to prove poor dietary patterns precede mental health problems)• 4-5 now

2. Treatment studies (to prove that improving nutrition removes mental health problems)• At least 45

FAST FOOD AND COMMERCIAL BAKED FOODS INCREASE THE RISK OFDEPRESSION, IRRITABILITY, ANXIETY

§Sequimiento Universidad de Navarra (SUN) Project in Spain, >16,000 former students and professors from Univ of Navarra, begun in 1999; ongoing.

§Semi-quantitative FFQ

Sanchez-Villegas et al., Public Health and Nutrition, 2012.

LONGITUDINAL STUDY OF DIET QUALITY AND MOOD

Dietary intake at baseline forØ Muffins, doughnuts, croissants:

summed to be ‘commercial baked goods’

Ø Hamburgers, sausage, pizza: summed to be ‘fast foods’

Added: 1 score indicating ‘unhealthy diet’ – and people were divided into thirds

RISK OF DEPRESSION AVERAGE OF 6.2 YEARS LATER, IN ~9,000 PEOPLE

1.00$ 1.02$

1.49$

0$

0.2$

0.4$

0.6$

0.8$

1$

1.2$

1.4$

1.6$

1.8$

LOWEST$Q1$ Q2$ Q3$

P for trend = 0.02

Ris

k of

dep

ress

ion

Consumption

Lowest third Middle third Highest third

AM I SAYING MUFFINS CAUSE DEPRESSION?

With every bite, we are making a choice

TO PROVE CAUSALITY

1. Prospective, longitudinal studies (to prove poor dietary patterns precede mental health problems)

2. Treatment studies (to prove that improving nutrition removes mental health problems)

SMILES TRIAL“IF I IMPROVE MY DIET, WILL MY

MENTAL HEALTH IMPROVE?”

Øn = 67, diagnosed with major depression

ØRandomized to diet counseling or social support: 7 sessions over 12 weeks

Jacka et al. (2017). BMC medicine, 15(1), 23.

SMILES TRIAL RESULTS1. Even with depression, diet modification is

possible and therapeutic2. 32% remission (diet) vs 8% (social support)3. Number needed to treat (NNT) = 44. Cost $112 AUS/week

Jacka, et al. (2017). BMC medicine, 15(1), 23.

None of these results are surprising if you know the HISTORY of research relating diet to mental health

1/18/18

WHAT DO THESE CHARACTERISTICS RESEMBLE?

ü Depressionü Hysteriaü Irritabilityü Self-mutilationü Apathy, lethargyü Social withdrawalü Inability to concentrate

SUBOPTIMAL NUTRITION!UNIV MINNESOTA STARVATION EXPERIMENTS, 1950

ü Depressionü Hysteriaü Irritabilityü Self-mutilationü Apathy, lethargyü Social withdrawalü Inability to concentrate

24 wks of nutrient deprivation in normal healthy students:

Treatment studies with nutrients in pill form

Terminology

• Micronutrient – definition varies

• Multinutrient formulas (e.g., B complex)

• Broad-spectrum formulas (25 or more nutrients)

WHICH COMMERCIAL MULTINUTRIENT FORMULAS HAVE ANY EVIDENCE

OF BENEFIT FOR MENTAL SYMPTOMS?

Alberta Broad-Spectrum Formulas

Ø EMPowerplus (www.Truehope.com)

Ø Daily Essential Minerals [DEN] (www.HardyNutritionals.com)

Ø For information and clinician guidance, please go to their websites.

Ø Both companies provide education and support to clinicians, as well as families

Ø Studied by independent scientists: from Canada, New Zealand, USA, and now Europe

Ø Companies never fund any scientist or any study

Ø Because of ethics committee requirements, the formulas have been reviewed by FDA and granted IND certificates

Ø They have also been scrutinized and approved by Health Canada

EVIDENCE FOR BROAD-SPECTRUM MICRONUTRIENTS IN:

1. Depression/bipolar disorder

2. Stress (e.g., after Natural Disasters)

3. ADHD

4. Anxiety

5. Psychosis

6. Explosive rage, sleep disturbance, recovery from

head injury

MICRONUTRIENTS FOR STRESS

7.1 EARTHQUAKE IN CHRISTCHURCH,NZ OCCURRED DURING ACTIVE TRIALS OF MULTINUTRIENT TREATMENT

Ø September 4th 2010 4:35am

Dr. Julia Rucklidge and her research team were evaluating broad spectrum mineral/vitamin formulas in the treatment of ADHD symptoms in a group of adults

185 people died, 7000 injured

Ø B complex, EMP low dose, EMP higher dose

Ø All 3 treatment groups showed improvements from baseline, more than controls (taking no nutrients)

Ø Groups taking broad spectrum formula improved more than B complex on some measures

ØFor symptoms of probable PTSD……

RCT WITH GENERAL POPULATION

0%10%20%30%40%50%60%70%80%

Control (n=25) Berocca (n=30) EMP4 (n=31) EMP8 (n=30)Baseline4 weeks

Rucklidge et al., 2012, Human Psychopharmacology

% m

eetin

g cr

iteria

for P

TSD

Alberta, June 2013

ALBERTA – NEW ZEALAND COLLABORATION

Ø Sample: 56 adults aged 23 – 66Ø Med-free, evidence of moderate depression and/or

anxiety on the Depression, Anxiety and Stress Scale (DASS)

Ø Placebo: unethicalØ Randomized to 3 groups – 6 week blinded RCT:

Ø Single nutrient (vitamin D 1000 IU): n=17Ø Few nutrients (B complex): n=21Ø Broad spectrum (~30 minerals and vitamins): n=18

Kaplan et al. (2015), Psychiatry Res

FLOOD STUDY RESULTS

0

5

10

15

20

25

Baseline Week2 Week4 Week6

VitaminD

BComplex

BroadSpectrumFormulaDAS

SStress

F(2,52)=3.81, p<.05; ES=0.76-0.88

Kaplan et al., Psychiatry Research, 2015

ØSometimes studies show that B complex alone is just as effective….

ØAt least 8 RCTs in nonclinical samples

ØGeneral population post-earthquake and post-flood benefited significantly from B complex

3 STUDIES NOW SHOW THE SAME THING

Ø HUMANS are more resilient to stress when they are better nourished

Ø As a supplement, providing even just B complex results in major benefit for acute stress*

*but not for a significant mood or anxiety disorder, or for explosive rage, etc……Why not the Fort Mac fires??

TAKE HOME MESSAGE

We eat for our brainsOptimal brain function requires a broad spectrum of minerals and vitamins for metabolism

4. SOCIETAL ISSUES

$$$$

THREATS TO OUR FOOD SUPPLY

COST OF CONVENTIONAL MENTAL HEALTH TREATMENT

0

50

100

150

200

250

300

350

2011 2021 2031 2041

Cost in $B

Canadian Mental Health Commission report, July 2012

“ANDREW”

Ø Middle child of 3; borderline IQ, moderately severe language problems

Ø Age 10: “stressed” and “overwhelmed”

Ø Disturbances in sleep, concentration, behaviour

Ø Auditory hallucinations, paranoid ideation

Ø Symptoms of Obsessive Compulsive Disorder (OCD)

Ø 6 months inpatient at Alberta Children’s Hospital, with many medication trials

Ø Discharged after 6 months unchanged

Ø Returned to outpatient care (Mood & Anxiety Disorders clinic; Dr. Megan Rodway)

Ø Parents suggested trying a broad spectrum micronutrient formula (EMPowerplus)

Ø Dr. Rodway: “This is snake oil, but I don’t have anything better to offer.”

What happened to Andrew?

(what happened to Dr. Rodway)

Daily psychosis symptom score10-day moving average

0

5

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25

30

10-Ja

n-09

10-Feb

-09

10-M

ar-09

10-Apr-09

10-M

ay-09

10-Ju

n-09

10-Ju

l-09

10-Aug-09

10-Sep

-09

10-Oct-09

10-Nov-09

Self-reported account of hallucinations

Visual hallucinations Auditory hallucinations

“ANDREW” BY 2010 (AND STILL IN 2018)

ØNo psychotic symptoms

ØGraduated high school in 2015

ØNo longer on any psychiatric medication

ØStill struggles with anxietyM Rodway et al, BMJ Case Reports, Nov 9, 2012

COST TO HEALTH CARE

Cost of conventional inpatient treatment

Cost of micronutrient outpatient treatment

Micronutrients cost

<2%of conventional

treatment

KAPLAN ET AL. (2017). HOSPITALIZATION COST OF CONVENTIONAL PSYCHIATRIC CARE COMPARED TO BROAD-SPECTRUM MICRONUTRIENT TREATMENT. INTERNATIONAL JOURNAL OF MENTAL HEALTH SYSTEMS,11:14. HTTP://RDCU.BE/OVB9

Ø diagnoses from 1997 (at age 33): bipolar disorder, depression, and PTSD.

Ø Avg annual cost of inpatient hospitalizations was $59,864; Ontario, BC, Alberta

Ø Dec 2001: Began cross-titration onto micronutrient formula and off medications

Ø From 2002 – present, zero medication and zero hospitalizations for mental health; self-funded micronutrients average annual cost of $760.

Figure 2. Annual costs for hospitalization, disability payments, and micronutrients. Hospitalization costs are based on data from Canadian Institute for Health Information (CIHI). Costs for provincial disability payments and self-funded micronutrients are patient-reported estimates. *Disability payments continued until 2009 as explained in the text.

$0$10,000$20,000$30,000$40,000$50,000$60,000

Hosp1997-2001

Disability1997-2001

Nutrientspriorto2001

Hospsince2002

Disabilitysince2009*

Nutrientssince2001

$59,864

$24,000

$0 $0 $0 $760

Cost(2015Canadian

dollars)

COST OF SUCCESSFUL TREATMENT WITH BROAD-SPECTRUM

MICRONUTRIENTS: < 2% AND < 10%

What could our societies do with that kind of cost savings?

MY VISION OF THE FUTURE

Ø Every clinician will say “There is increasing evidence that how we eat affects how we feel. Let’s talk about your diet.”

Ø Every mental health clinic will teach cooking, educate about nutrition and mental health.

Ø Every child will have the opportunity of being given broad-spectrum micronutrients for emotional/behavioural challenges…….before ever being exposed to medication.

1/18/18

ØOffices and workplaces will create a culture of health, including healthy food and exercise

ØConsumers will demand nutrient-dense food

ØFarmers will be rewarded for nutrient density, not yield

1/18/18

KAPLAN@UCALGARY.CA

Ø Request my slidesØ Join my email updates listØ Connect me to potential donors for the 2 charitable

funds.Ø But, for questions about the Alberta Formulas, please

contact the companies:Ø Daily Essential Nutrients (DEN)

hardynutritionals.comØ EMPowerplus: truehope.com

How to reach me