Download Repair/Recovery/Plasticity

NUTRITIONAL SUPPLEMENTS
TO BOOST THE BRAIN:
THE ROLE AND EVIDENCE FOR NUTRACEUTICAL USE
SuAnn Chen, MD
ABPMR Board Certified in Physical Medicine & Rehabilitation
Subspecialty Certified in Brain Injury Medicine
Medical Director, Brain Injury Rehab Program
Good Shepherd Rehabilitation Network
Allentown, PA
Brain Injury Association of Pennsylvania
Annual Conference
June 29, 2015
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NO DISCLOSURES
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Lecture Outline
Background
Targeted Mechanisms of Actions in TBI
• Fuel/Energy/Metabolism
• Antioxidant/Anti-inflammatory
• Repair/Recovery/Plasticity
• Mood/Behavior
Select Nutraceuticals and Prior Research Studies
• Branched Chain Amino Acids
• Fish Oil
Recommendations
• Curcumin
• Citicoline
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Who uses nutritional
supplements?
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Ever had these?
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What is a ‘Nutraceutical’?
• Term coined in 1989 by
Stephen DeFelice, MD,
founder and chairman
of Foundation of
Innovation in Medicine
• ‘Nutrition’ +
‘Pharmaceutical’
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What is a ‘Nutraceutical’?
• More recently (2010) defined in an article in
International Journal of Pharmacy and
Pharmaceutical Sciences:
“a food or part of a food for oral administration with
demonstrated safety and health benefits beyond the basic
nutritional functions to supplement diet, presented in a
non-food matrix or non-conventional food formats, in such
a quantity that exceeds those that could be obtained from
normal foods and with such frequency as required to
realize such properties”
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Brain Boost Supplements
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Is any of this stuff worth it?
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Approach for Selecting Nutritional
Interventions: Mechanistic Targets
Fuel/Energy/
Metabolism
Antioxidant/
Antiinflammatory
Repair and
Recovery/
Plasticity
Mood/Behavior
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CHOOSING NUTRACEUTICALS:
Mechanistic Targets:
Fuel/Energy/Metabolism
Acetyl-L-Carnitine
Branched Chain Amino Acids
Creatine
Ketogenic Diet
“Medical Food”
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Branched Chain Amino Acids
(BCAAs)
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Branched Chain Amino Acids
(BCAAs)
Mechanism:
Building blocks of proteins
Regulatory control of protein metabolism
• Marketed to healthy individuals to enhance muscle mass, reduce central fatigue, reduce
soreness after exercise
In the brain:
• Important for the production of neurotransmitters as a nitrogen donor
• Competes for transport across blood-brain barrier with Trp, Tyr, Phe
No adverse effects noted, even at high doses
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Branched Chain Amino Acids
(BCAAs)
Prior human studies (in TBI):
Aquilani et al, 2008
• Randomized, placebo-controlled trial
• N=41 rehab pts in severe disorder of consciousness
• Given 15 days IV BCAA supplementation
• Results:
• Disability Rating Scores improved significantly, while placebo unchanged
Aquilani et al, 2005
• Randomized, placebo-controlled trial
• N=60 men with TBI
• Given 15 days IV BCAA supplementation
• Results:
• Disability Rating Scores improved significantly for both groups, (p <0.02), but
treatment group significantly greater (p <0.004)
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Branched Chain Amino Acids
(BCAAs)
Prior animal study (in TBI):
Cole et
al, 2010
• Adult male mice, 5-7 weeks old
• Given a TBI by lateral fluid percussion injury
• 2-days post-injury, given dietary oral BCAAs, for 5 days
• Results:
• BCAA levels are no different from sham mice
• In behavioral assessments, treated mice behave no
differently
• In vitro analysis of hippocampal slices from injured mice
then incubated with BCAA -> FULLY RESTORED SYNAPTIC
FUNCTION
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Branched Chain Amino Acids
(BCAAs)
Conclusions:
-Important benefit in increasing protein synthesis and lean body mass
-Only a few positive studies in TBI, the animal study is promising
-Not enough evidence to support BCAA supplementation for TBI
-Keep an eye out on future studies
Currently… Upenn study – THIN for sports-related concussions…
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CHOOSING NUTRACEUTICALS:
Mechanistic Targets:
Antioxidant/Anti-inflammatory
Vitamin E
Alpha-lipoic acid
Vitamin C
Fish oil (Omega-3, DHA, EPA)
Vitamin D
Curcumin
Coenzyme Q10
Ginkgo Biloba
D-ribose
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Fish oil
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Fish oil
Mechanism:
Structural component in cell membrane biphospholid layers
Antioxidant
• Reduces synthesis of inflammatory cytokines such as IL-1 and TNF
• Precursors for resolvins (programmed resolution of inflammatory processes)
• Precursors of protectins (anti-inflammatory agents)
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Fish oil
Prior human studies (in TBI): No clinical trials
Cochrane Review of omega-3 fatty acid for
prevention of cognitive decline and dementia, 2012:
• Included 3 studies, n=3536 participants
• Results:
• No benefit to cognitive function among cognitively healthy older
people who took a variety of cognitive tests at baseline and final
follow-up, including MMSE and tests of memory and executive
functions
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Fish oil
Prior animal studies (in TBI):
Mills et al, 2010
Wu et al,
2007
• Traumatic axonal injury, impact acceleration injury on adult, male rats
• Post-injury, oral n-3 fatty acids or no treatment
• Results:
• Injured rats without n-3 fatty acids had more amyloid precursor protein-labeled axons
• Mild fluid percussion injury on rats
• Pre-injury diet supplemented with fatty acids vs. regular diet for 4 wks
• Results:
• Levels of oxidized protein increased after injury, but reduced by n-3 fatty acid
supplementation
• Mitochondrial creatine kinase reduced in injured rats, but restored with n-3 fatty acids
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Fish oil
Conclusions:
-So far, not promising studies in stroke literature and in cochrane review
for cognitive impairment and dementia
- BUT animal models are promising and more human studies should be done
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Curcumin
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Curcumin
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CHOOSING NUTRACEUTICALS:
Mechanistic Targets:
Repair/Recovery/Plasticity
Curcumin
Huperzine A
Ginseng
Citicoline
Phosphatidyl Serine
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Citicoline
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Citicoline
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Citicoline
Mechanism:
Building blocks of phospholipid membranes
Accelerates the synthesis and release of acetylcholine
Major dietary source of methyl groups
Antioxidant
Essential element in neurodevelopment
Decreases apoptosis
Adverse effects: Fishy body odor, Hypotension, others
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Citicoline
ICTUS trial
August 2012
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Citicoline
IDEALE Study
February 2013
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Citicoline
COBRIT trial
November 2012
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Citicoline
Conclusions:
- Still used in Europe for Alzheimer’s, Parkinson’s, cognitive impairment
- Still used in Japan to increase level of consciousness after TBI
and for ischemic stroke
- Recent disappointing big trials, but possibly still promising
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CHOOSING NUTRACEUTICALS:
Mechanistic Targets:
Mood/Behavior
Methylfolate
Methylcobalamin
S-adenosylmethionine (SAM-E)
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Folic Acid & Methylfolate
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Recommendations
• No definite evidence yet
• But very few adverse effects reported
• More studies needed
(some nutraceuticals more important
now than others)
• Likely can not just target one mechanism,
need a combination
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Questions??
Thank You
Acknowledgements:
• Dr. Jonathan Fellus
• Dr. Elliot Roth
• Dr. David Ripley
• My husband, Jim Yang
• References available