Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine ......P13 P14 3.5 2.5 GSH 7 0 10 20 6030 40...

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Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine Symposium Mar 28, 2019 &

Transcript of Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine ......P13 P14 3.5 2.5 GSH 7 0 10 20 6030 40...

Page 1: Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine ......P13 P14 3.5 2.5 GSH 7 0 10 20 6030 40 so Time (min) 70 P15 model residual \ I 3.5 572.5 I SH:Cr Mea n m id - ,, poi nt

Laurie K Mischley, ND PhD MPH

OHSU Integrative Medicine Symposium

Mar 28, 2019

&

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Disclosures

• Advisory Boards: Brian Grant Foundation, Next Frontier Biosciences

• Founder: NeurRx, Social Purpose Corporation

• ParK-9: Dogs that identify the scent of parkinsonism

• Parkinson’s School (online)

• Owner of PRO-PD scale (free scores available at www.PROPD.org)

• Institutional Affiliations: Bastyr University, National College of Naturopathic

Medicine

• Clinical Practice: Seattle Integrative Medicine

• Medial Director of PD Summer School @ Bastyr University

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My bias:

Patient-Centered Pragmatic Research

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Conditionally Essential Nutrients in PD

“Humans are parasites of the

planet. In order to sur- vive,

there are minerals and

molecules, ultraviolet waves,

and other organisms on which

we rely. We need some of

Earth’s resources to function

optimally and in some cases,

we need them to function at all.

These nutrients on which we

rely are considered essential

nutrients if they are used by

most humans most of the time.”

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Does Diet Influence Risk of Developing PD?

• Increased Risk

• Red meat, processed

meat

• Dairy

• Refined grains

• Desserts & sweets

• Well water

• Pesticides

• Decreased Risk

• Vegetables

• Legumes

• Fruit

• Fish

• Coffee

• Tea

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Diet & PD Symptoms

• Malnutrition is common in PD

• Associated with:

• Constipation

• Depression

• Anxiety

• Cognitive impairment

• Dystonia

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What About Diet and RATE of Progression?

?

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What is Parkinson’s?

(According to Patients)

Mischley LK 2017

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Measuring PD Progression

• Ideal scale:

• Administered remotely

• Patient-centered

• Correlates with quality of life

• Correlates with established measures of disease

severity

• Continuous, stratifiable by symptom, sensitive enough

to detect slight change • www.PROPD.org

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Are Patient-Reported Outcomes Accurate?

www.CAMCarePD.bastyr.edu

Mischley LK 2016

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What are the POSITIVE DEVIANTS

doing differently?

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Diet: Encourage

• Fresh veggies

• Fresh fruit

• Nuts & seeds

• Non-fried fish

• Olive oil

• Coconut oil

• Wine

• Spices

• Fresh herbs

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Diet: Avoid

• Red meat, processed meat

• Dairy

• Cheese

• Yogurt

• Ice cream

• Fried foods

• Soda / Diet soda

• Canned Fruits

• Canned Vegetables

Mischley LK, 2016. Diet & Supps in PD

Progression.

https://www.huffingtonpost.com/2014/08/15/french-fries-healthy- fast-food_n_5678580.html

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Diary: Why the link with PD?

➤ 5 studies suggest the more dairy

you eat, the more likely you are

to be diagnosed with PD

➤ CAM Care study showed the

more dairy people consumed,

the worse their symptoms over

time.

Mischley LK 2017

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Does it Matter if It’s Organic?

“I try to eat organically grown

foods when possible.”

We surveyed over 1000 PwP.

People who responded TRUE

had a PRO-PD score

approximately 75 points lower

than those who don’t make the

effort (-74.9 (28.1); p=0.008 (-130

to -19.8)).

Data after adjusting for age, gender,

income, and years since diagnosis.

(Mischley et al 2017)

Mischley LK 2017

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Nutraceuticals Associated With

Rate of Progression

• Improved Outcomes

• Coenzyme Q-10

• Fish oil

• Worse Outcomes

• Iron supplements

• (Melatonin seemed to be due to poor sleep, not the melatonin.)

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Coenzyme Q10 in PD

• QE3 study vs. Phase I, Phase II, & population studies

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Fish Oil

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Does fish oil reduce dyskinesia in humans?

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• Associated with:

• Slower bowel transit time

• Elevated hsCRP

• Impaired balance, muscle weakness

• Depression

• Risk of dementia

• Required dose depends on: obesity, time outdoors, coverage of skin.

• Potentially toxic (Toxicity occurs ~ 300 ng/ml (Jones 2008).)

PD

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Assessing Lithium Status

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• Due to interference with folic acid, B12, etc.

• Elevated homocysteine can be neurotoxic. Associated with:

• Dementia, l-dopa-related behavior abnormalities

• PD Progression (accelerates neurodegeneration)

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Glutathione

• Depletion comes before mitochondrial

dysfunction,

• Protein aggregation, Lewy body formation, or

• Cell Death, loss of dopamine.

• Augmentation strategies have been explored

since the 80’s.

• Reduced glutathione (GSH) is the primary

antioxidant of the central nervous system (CNS).

• ~40% deficiency of brain GSH in early PD.

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0.1

b "I' t

npJ Parkinson's Disease www.nature. com/npjparkd

All rights reserved 2373-8057/16

ARTICLE OPEN

Central nervous system uptake of intranasal glutathione in

Parkinson's disease 2 3 1 4 2 5 6

Laurie K Mischley 1' ' , Kevin E Conley1, Eric G Shankland , Terrance J Kavanagh , Michael E Rosenfeld A, John E Duda ' ,

Collin C White4

Timothy K Wilbur 1

Prysilla U De La Torre 1 3

and Jeannie M Padowski7 8

, , ' '

Figure 4. Volume of interest. For all participants, glutathione (GSH) was administered into the left nostril, and a voxel was placed over a 4 x 4 x 5-cm region centered on the left dorsal putamen at the level of the lentiform nucleus.

Individual Results

GSH

data

.

OPJ Parkinson's Disease

0.06

c: 0.05

QJ u QJ

·.§ 0.04 QJ "'

0.03

0

0.02

0.01

-P01

- po2

0.00 +--- - --- -

Time ( min)

0.0 10.0 20.0 30.0 40.0 50.0 60.0

-P03 P04

- POS

-P06

-P07

P09

GSH

data

mflfila1

P10

-p11

-P12

P13

P14

3.5 2.5

data

GSH

0 10 20 30 40 so Time (min)

60 70 P15 model residual

\ I

3.5 2.5

I

G SH:Cr

Mea n m id - ,,

poi nt o sca n

ti me as m i n

post-dose

(SE )

Su bjects

( = 15)

M ea n (SD)

M i n

Max

M ea n

cha n ge

rel a tive to

basel i ne

(SEM)

0 [Ba seline] 9 0 .026 (0.01 8) 0.007 0.06.2 7 .6 (0.3) 14 0.025 (0.016) 0.008 0.058 0 .00800

20 (0.37) 13 0.036 (0.02.2) 0.012 0.076 0.0194

32 (0.36) 14 0 .038 (0.02 1) 0.013 0.081 0.02.2 1

45 (0.47) 9 0 .045 (0.037) 0.013 0. 1 14 0.0350

57 1 0.049 0.049 0.049 0.025

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Phase I & II Studies (in)GSH in PD

• Safe & tolerable.

• Observed motor improvement in both; an appropriately-

powered Phase III study is required to determine whether

(in)GSH is better than placebo.

Mischley LK. Phase I Study of Intranasal glutathione for PD. 2015

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Glutathione Augmentation Trials in PD

treatment arms &

placebo has

symptoms.

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Intranasal Glutathione Research

Next steps:

Are motor improvements sustained?

Does (in)GSH affect rate of progression?

+ product development work

LKMischley 2018

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How to Test for Nutritional Deficiencies

• Blood

• Urine

• Hair

• Stool

• Breath

• MRS

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Nutrition Resources

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https://www.hindawi.com/journals/omcl/2017/6405278/

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Thank You!

LK Mischley Contact:

Clinic: [email protected]

Academic: [email protected]

Other: info@EducationIsMedicine