Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine ......P13 P14 3.5 2.5 GSH 7 0 10 20 6030 40...
Transcript of Laurie K Mischley, ND PhD MPH OHSU Integrative Medicine ......P13 P14 3.5 2.5 GSH 7 0 10 20 6030 40...
Laurie K Mischley, ND PhD MPH
OHSU Integrative Medicine Symposium
Mar 28, 2019
&
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
My bias:
Patient-Centered Pragmatic Research
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.”
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
Diet & PD Symptoms
• Malnutrition is common in PD
• Associated with:
• Constipation
• Depression
• Anxiety
• Cognitive impairment
• Dystonia
What About Diet and RATE of Progression?
?
What is Parkinson’s?
(According to Patients)
Mischley LK 2017
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
Are Patient-Reported Outcomes Accurate?
www.CAMCarePD.bastyr.edu
Mischley LK 2016
What are the POSITIVE DEVIANTS
doing differently?
Diet: Encourage
• Fresh veggies
• Fresh fruit
• Nuts & seeds
• Non-fried fish
• Olive oil
• Coconut oil
• Wine
• Spices
• Fresh herbs
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
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
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
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.)
Coenzyme Q10 in PD
• QE3 study vs. Phase I, Phase II, & population studies
Fish Oil
Does fish oil reduce dyskinesia in humans?
• 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
Assessing Lithium Status
•
• 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)
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.
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
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
Glutathione Augmentation Trials in PD
treatment arms &
placebo has
symptoms.
Intranasal Glutathione Research
Next steps:
Are motor improvements sustained?
Does (in)GSH affect rate of progression?
+ product development work
LKMischley 2018
How to Test for Nutritional Deficiencies
• Blood
• Urine
• Hair
• Stool
• Breath
• MRS
Nutrition Resources
29
https://www.hindawi.com/journals/omcl/2017/6405278/
Thank You!
LK Mischley Contact:
Clinic: [email protected]
Academic: [email protected]
Other: info@EducationIsMedicine