What Functional Medicine tell you about:

A, B, C ‐ Embolic Stroke
D, E ‐ Large Artery Stroke
F ‐Small Artery Stroke
RED STROKE WHITE STROKE
Frontal lobe Motor cortex
Executive functions, Movement Sensory cortex
thinking, planning, Sensations
Parietal lobe
organizing and Perception, making
problem solving, Sense of the world,
emotions and arithmetic, spelling
behavioural control
personality
Stroke April 1, 2006 vol. 37 no. 4 1129-1136
FUNCTIONAL MEDICINE
POINT OF VIEW
 FM

- Each heartbeat, blood is thrust into arteries

- branch into smaller arterioles
- branch further into capillaries
Æ deliver oxygen and nutrients to cells.27
- Just how tiny capillaries that oxygenate neurons
- Red blood cell is 6-10 micrometers,
(capillary diameter is only 8-10 micrometers)27,28
- Capillaries so narrow : RBC have to bend their shape 29
- Platelets 2-4 micrometers,30
Æ thrombosis creates a mass that cannot fit through
Æ thread-like capillaries.31
Æ how precarious our aging cerebral vascular
Æ hypoperfusion develops
- Not only are capillaries tiny (but extremely delicate).
- Instead of the tough layers that make up arteries,
Æ capillaries consist only single layer of endothelial29,32
- Hypertension destroys fragile capillaries
Æleaving wake hypoperfused regions of the brain,
Æ cerebral perfusion deficits33
- Capillaries surround neurons, diffuse O2 & nutrients33
Æ Interruption to capillary blood flow : injure or kill neurons.33
Æ hypoperfusion must be prevented or reversed
- Abnormal platelet aggregation increases as humans age
Æ thrombosis is an increasing threat with aging.34,35
- Particle > than 5-10 micrometers can clog capillaries,
- If enough capillaries occluded
Æ ischemic stroke can occur.33
Risk factors: - homocysteine,36
Æ creates more havoc at the capillary40
- fibrinogen,37
Æ promotes occlusive thrombosis41
- C-reactive protein,38
Æ damages the delicate endothelium
- triglycerides.39
Æ clog capillary beds
- Hypoperfusion: severely diminish neurological function.
Æ structural changes adversely impact aging brain
Æ structural deterioration
Æ decline in microvascular blood flow.
- Researchers recognizing :
most aging suffer obstructions to cerebral blood flow
Æ chronic hypoperfusion.1
Æ cascade of neuronal injuries
(memory loss2, depression,3-6 & cognitive dysfunction7-9)
Æ long-term impact of hypoperfusion
(stroke,10,11 vascular dementia,12,13 & Alzheimer’s14-16)
- Aging ≈ ↓↓ blood flow to the brain (hypoperfusion)
Æ causes cell injury and death.17
Æ Hypertension accelerates brain atrophy in humans.18
Æ damaging the cerebral circulatory system.19,20
HYPOPERFUSION
(cerebrovascular insufficiency)

• 15% lower in those with metabolic syndrome

Æ related to heart deficiencies
Æ 14 years later44
(abnormal EKGs and nighttime BP dipping)

• Silent
myocardial ischemia ≈ cerebrovascular disease
Æ Nocturnal BP dipping ≈ MCI
Æ mild cardiac disturbances
Æ deprive brain blood flow
Æ cognitive impairments
(a) ACUTE - ATTACK
3 hypoperfused tissue (the core, the penumbra and the oligaemia)
exhausted vascular reserve (denoted autoregulated)
(b) DECREASE CEREBRAL PERFUSION
fall in systemic blood pressure or an increase in intracranial pressure
(vasogenic oedema)
Æ an enlargement of the core at the expense of the penumbra
Æ later into the oligaemia and autoregulated compartments,
infarction potentially involves all four compartments entirely.
Left brain stroke with CT showing large hypoperfused area supplied by the middle cerebral 
artery. Panels B‐D show cerebral perfusion and allow doctors to make decisions based on the 
status of blood flow to the brain.
Severity of Hypoperfusion
Predicts risk of sICH
Functional Medicine: Web‐like interconnections in Stroke
 MATRIX  COMPLAINT LAB
hs CRP, Cortisol, 
IMMUNE & INFLAMMATORY Smoke, diabetes, gum disease, 
fasting Insulin,
overweight, craving carbohydrates, 
Complement 
constantly hungry,  tired (especially 
Hypogammaglob
after exercise), fingernails brittle, 
Leukocyte count 
constipated,  groggy upon waking,  
IgA , 
difficulty concentrating, headaches, 
Lymphocyte 
sinusitis, carries, diarrhea, etc
count
Heavy metal, 
ENVIRONMENTAL INPUTS Headache, fever and chills, nausea, 
metabolic 
cough, bloating, muscle aches, skin 
profile, Different 
rash, itchy, watery eyes, and some 
count, 
congestion, allergy, anxiety, moody, 
spirometr, hair 
abdominal cramp, short of breath, etc
test
OXIDATIVE STRESS increased tanning, especially on skin‐ LDL, antioxidant, 
folds, scars, elbows, knees; black  pH urine, FR test
freckles, fingers white, numb, stiff,  Electron Spin 
swellings, red or purplish spots under  Resonance test
the skin, bruises easily, etc
 MATRIX  COMPLAINT LAB
HORMONE &  Persistent weight gain, low libido,  loss  Hormone panel, 
NEUROTRANSMITTER of muscle mass, fatigue, anxiety,  wellness marker
IMBALANCE irritability and depression, Insomnia 
and poor sleep patterns, sweating, 
digestion problems, craving, etc

MIND, SPIRIT & EMOTION  Block higher consciousness, vibrations  PNEI marker

IMBALANCES and energies accelerate stuckness or 
stagnation , resistances,  migraine, 
headache, tingling sensations, heat 
esp spine, head, hands and feet, Past 
life scenarios may play out, speaking 
copiously and quickly, etc

STRUCTURAL IMBALANCE Weakness , neuropathic pain, absent  Anio gap, BUN,  

reflexes, gastrointestinal problem,  CK, CBC (anemia, 
GeRD, delayed gastric emptying,  neutropenia, 
constipation, fainting, absent or  thrombocytopen
excessive sweating, etc ia)
 MATRIX  COMPLAINT LAB

GASTRO‐INTESTINAL fatigue, headache, stomach upset,  CCK, CHE, GI test

nausea, diarrhea, constipation,  Enzyme profile
dizziness, musculoskeletal pains,  Liver function
Stomach pain, Flatulence (gas), Bloat  etc
or swollen abdomen, Diarrhea, 
constipation or a combination of both
Whitish mucus in the stool, panic 
disorder, anxiety, unexplained weight 
loss, persistent, low‐grade fever,
feeling bloated or full after eating very 
little, blood in the stool, having a 
bowel movement that is black, tarry 
and foul smelling, etc

DETOXIFICATION Sinus congestion, indigestion, hives,  Urine organic

bloating, irritability, fatigue,  Hair test
headaches, joint pain, weight gain,  SGOT, SGPT
insomnia, fuzzy thinking, coughing,  etc
sneezing, constipation or chest pain.
 Salvaging penumbra is the goal Energetic
for acute stroke treatment.
↓
Bioenergetic
pathway
↓
therapeutic modality
↓
recanalizational therapies

C1-C9:
pathological cycles
between major events

Q1-Q3:
suspected pathological
cycles between
major events

Journal of Experimental Stroke and Translational Medicine: 
January 2010, Vol. 3, No. 1, pp. 47‐55
 (Periwinkle plant)

Mechanism of action
• selectively inhibit voltage-sensitive Na+ channels
Æ evoked extracellular Ca+ ions in striatal nerve
Neurochemistry International 46 (7): 533–40
• Na+ channel inhibiting: neuroprotective effect
Æ blockade of excitotoxicity and
Æ attenuation of neuronal damage
Æ induced by cerebral ischemia/reperfusion
Orvosi Hetilap (in Hungarian) 141 (23): 1279–86.

• PDE-1 inhibitor
( IC50: ±10−5 M): ↑intracellular cGMP
Æ vasorelaxant cerebral smooth muscle tissue
Biochemical Pharmacology 33 (3): 453–7
Urological Research 24 (3): 129–34
• Inhibits IKK preventing IκB degradation
Æ translocation NF-κB to the cell nucleus.
Proceedings of the National Academy of Sciences 107 (21): 9795–9800.
Proceedings of the National Academy of Sciences 107 (22): 9921–9922.

• Increases neuronal levels of DOPAC

Æ a metabolic breakdown product of dopamine
Æ biogenic pharmacology of reserpine
(structural relative of vinpocetine)
Æ depletes catecholamine levels
Brain Research 909 (1–2): 59–67.

• Clinical studies used vinpocetine 10 mg 3dd

• Novel anti-inflammatory agent

Æ up-regulation of NF-κB by TNFα
Æ ↓ IL-1 beta, MCP-1 (monocyte chemoattractant protein-1),
and VCAM (vascular cell adhesion molecule-1)
. Proceedings of the National Academy of Sciences 107 (21): 9795–9800
• exhibit anticonvulsant properties
Æ effect on amygdala-kindled and neocortical
Æ abolished [3H]Glu release
Æ after in vivo exposure to 4-aminopyridine (4-AP)
Æ important mechanism for vinpocetine
Biomedica biochimica acta 49 (5): 413–9.
Epilepsy research 96 (3): 257–66.
• cerebral blood-flow enhancing
• neuroprotective effects,
(used as a drug in Eastern Europe)
Æ cerebrovascular disorders
Æ age-related memory impairment.
Journal of the Neurological Sciences. 229-230: 275–284.
Acta pharmaceutica Hungarica 72 (2): 84–91
Alternative Medicine Review 7 (3): 240–3. 2002.
• vasodilation and as a nootropic
Æ cerebral metabolism
Proceedings of the National Academy of Sciences 107 (21): 9795–9800.
Acta Pharm Hung. 1996 Sep;66(5):213-24
Cavinton study (treatment of cerebrovascular disorders)
- pharmacological research of cognitive deficits
Æ 5 main pharmacological and biochemical actions:
(1) ↑ brain circulation and O2 utilization without
significant alteration in systemic circulation,
(2) ↑tolerance of brain toward hypoxia and ischemia,
(3) anticonvulsant activity,
(4) inhibitory effect on PDE enzyme and
(5) improve rheological properties of the blood and
inhibition of aggregation of thrombocytes.
- evidence that neuroprotective action
● inhibition of voltage neuronal Na(+)-channels,
Æ rise of intracellular Ca(2+)-levels
Æ inhibition of adenosine reuptake
Æ selective inhibitor of Ca(2+)-calmodulin
Æ enhances intracellular a GMP levels
Biochem Pharmacol. 1984 Feb 1;33(3):453-7

- a novel vasodilating agent,

- inhibits Ca2+-dependent phosphodiesterase,
Æ selectively, of cyclic nucleotide PDE
Æ producing 50% inhibition of Ca2+
- increasing CaM
- increases cyclic GMP levels
Æ no significant effects on cyclic AMP levels.
- pharmacological evidence
Æ that Ca2+-dependent phosphodiesterase mainly
hydrolyzes cyclic GMP in vascular smooth muscle.
- induce vascular relaxation
Æ increasing cyclic GMP
Æ selective inhibition of Ca2+-dependent PDE.
Neurochem Int. 2005 Jun;46(7):533-40
anticonvulsant action
- changes on internal concentrations of Na(+) (Na(i))
and Ca(2+) (Ca(i)) in striatal isolated nerve endings.
- voltage-sensitive sodium channels (VSSC)-mediated
Æ activation of pre-synaptic Ca(2+) channels.
- inhibitory effect on pre-synaptic voltage-sensitive Na

Epilepsy Res. 2011 Oct;96(3):257-66.

≈ 4-Aminopyridine (4-AP)
- induced Glu release
- direct blockade of presynaptic Na+ channels
Æ anticonvulsant actions
- increase some K+ channels permeability.
Pharmaco Report 2011. 63: 618-628

- exhibits cerebral blood-flow enhancing

- neuroprotective effects
- vasodilation activity
- a nootropic for improvement of memory

Zh Nevropatol Psikhiatr Im S S Korsakova.

1991;91:21-22
- hypoxic ischemic encephalopathy
Group 1: 20 patients conventional therapy;
Æ seizures disappeared in 6 patients.
Group 2 included 41 patients given Vinpocetine;
Æ seizures disappeared in 27 patients.
- No convulsive syndrome was recorded in group 2;
Æ normalization of psychomotor development
Eur J Clin Pharmacol . 1985;28:567-571.
- randomized, double-blind, crossover study,
- 12 women receiving either vinpocetine
- critical flicker fusion, reaction time & a Sternberg Test
Æ significant changes in Sternberg Memory Scanning

Int Clin Psychopharmacol . 1991;6:31-43.

- psychopharmacotherapy
16-week, placebo-controlled, randomized,
double-blind, multicenter trial,
203 patients vinpocetine 10 or 20 mg (3dd) or placebo
Æ assessed Clinical Global Impression scale
Æ statistically significant improvements in all tests.
Acta Pharm Hung . 2002;72:84-91.
- significantly decreased infarct volume (42%; P < 0.05)
Æ compared with that of flunarizine or nimodipine.
- reduce development of atherosclerosis
- decreased calcium content in various organ systems

Arzneimittelforschung . 1992;42:425-427.
- increasing red blood cell deformability
Æ compared with single oral doses of pentoxifylline 300 mg
and nicergoline 20 mg

Eur J Neurol . 2001;8:81-85.

- poststroke patients.
Æ glucose transport (intracellular uptake and release)
Æ utilization of glucose in the brain in hemisphere
(in acute ischemic and chronic stroke)
J Neuroimaging . 1998;8:197-204
- A pilot, single-blind, randomized trial
- examined the effect of vinpocetine
- 30 patients with acute ischemic stroke
- treated within 72 hours of stroke onset.
Æ vinpocetine-treated group marginally better at 3 months
(P = 0.05, ANOVA).

J Neurol Sci . 2005;229-230:275-284.

- patients with ischemic stroke
- double-blind, randomized, placebo-controlled study.
- a single dose of vinpocetine IV 20 mg in NaCl 500 mL
- or NaCl 500 mL alone as placebo.
- transcranial Doppler and near infrared spectroscopy
Æ ↑cerebral perfusion and parenchymal O2 extraction
Brain Res Bull . 2000;53:245-254.
neuroprotective action of vinpocetine is associated with
its effect on calcium- and calmodulin-dependent cGMP
Æ voltage-operated calcium channels, glutamate
receptors, and voltage-dependent sodium channels

J Am Geriatr Soc . 1987;35:425-430.

- double-blind clinical trial,
- 42 patients chronic vascular senile cerebral dysfunction
- received vinpocetine 10 mg 3 times daily for 30 days
- followed by 5 mg 3 times daily for 60 days.
- Placebo given to another 42 patients over 90 days.
Evaluations: Clinical Global Impression scale,
Sandoz Clinical Assessment-Geriatric scale,
and Mini-Mental Status Questionnaire
Æ consistently higher in patients receiving vinpocetine.
Æ No serious side effects were reported
 (Huperzia serrata)

Pharmacological effects
• acetylcholinesterase inhibitor
• NMDA receptor antagonist.
• neurodegeneration activity
• improve memory and mental function.
Journal of neural transmission (Vienna, Austria : 1996) 116 (4): 457–65.
Drugs of the Future 24 (6): 647.
Current medicinal chemistry 7 (3): 355–74.
Chemico-biological interactions 175 (1–3): 387–95.

• Huperzine A 0.2 to 0.4 mg/day

http://www.fda.gov/ohrms/dockets/dockets/95s0316/rpt0015_01.pdf
Cochrane Database Syst Rev. 2008;(2):CD005592.
Ann Pharmacother . 2009;43(3):514-518.
• combination of : anticholinesterase activity and
antiglutamate, antioxidant, and
neuroprotective effects

Neurotoxicology . 2002;23(1):1-5.
• crosses the blood-brain barrier more effectively than
tacrine or donepezil and
• acts with greater potency than tacrine, physostigmine,
or galanthamine.

Pharmacol Biochem Behav. 1998;60(2):377-386.

• selective for brain acetyl cholinesterase over plasma
butyryl cholinesterase
Ann Pharmacother . 2009;43(3):514-518.
• increase in general cognitive function, global
clinical status, behavioral disturbances, and
physical performance.

Drugs Aging . 2003;20(13):981-998.

• 1 review of 4 clinical trials
- improvement against memory & dementia
- improve Alzheimer scales
- meeting inclusion criteria for vascular dementia.

Drugs R D. 2004;5(1):44-5
• putative nootropic agent
Æ phase III clinical trial
• slow reversible inhibition of acetylcholinesterase
Æ phase II clinical trial
Cell Mol Neurobiol. 2008 Feb;28(2):173-83.
• acetylcholinesterase inhibitors
Æ ↓ breakdown of neurotransmitter acetylcholine
Æ mild to moderate Alzheimer's patients
• have non-cholinergic functions
Æ reduce formation and deposition of beta-amyloid.
• a potent and reversible inhibitor of acetylcholinesterase
Æ improve cognitive deficits
• the novel neuroprotective effects
• potential new selective and powerful anti-Alzheimer's
• PRESENT PAPER
Æ neuroprotective effects
Æ acetylcholinesterase inhibition
Æ regulating beta-amyloid precursor protein metabolism
Æ protect against beta-amyloid-mediated ROS
Æ protect against apoptosis.
Trends Pharmacol Sci. 2006 Dec;27(12):619-25.
• neuroprotective effects
Æ beyond inhibition of AChE.
• ameliorate learning and memory deficiency
• modification of beta-amyloid peptide
Æ reduction of oxidative stress,
Æ neuronal protection against apoptosis
Æ regulation expression and secretion of NGF
(nerve growth factor) and NGF signaling.

Neurosignals. 2005;14(1-2):71-82.
• possesses the ability to protect cells against
(1) hydrogen peroxide, (2) beta-amyloid protein (or peptide),
(3) glutamate, (4) ischemia and (5) staurosporine-induced
cytotoxicity and (6) apoptosis.
Acta Pharmacol Sin. 2006 Jan;27(1):1-26.
• ability to attenuate oxidative stress
• regulate expression apoptotic proteins
Æ Bcl-2, Bax, P53, and caspase-3,
• protect mitochondria,
• upregulate nerve growth factor and its receptors
• interfere amyloid precursor protein metabolism.
• neuroprotection
Æ antagonizing on N-methyl-D-aspartate receptors
and potassium currents
• indicated HupA was absorbed rapidly
Æ no unexpected toxicity (hepatotoxicity)
• phase IV clinical trials in China
Æ significantly improved memory deficits
Æ minimal peripheral cholinergic side effects
• protective agent against organophosphate intox.
• antioxidant effect on primary astrocytes
Æ reduction of astrocytic death induced by H(2)O(2).
Æ increased cell viability
• antioxidant enzymes capacity
Æ catalase (CAT), superoxide dismutase (SOD),
glutathione peroxidases (GPx) and glutathione
reductase (GR),
Æ reduced and oxidized on the intracellular ROS
Ethnopharmacol. 2007 Jun 13;112(2):262-70.

• active ingredient as neuroprotection

Æ Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-
Re, Gensenoside-Rd and Panax notoginseng saponins
World Journal of Neuroscience, 2014, 4, 12-17 WJNS
 Panax Ginseng
Oriental Ginseng American Ginseng Siberian Ginseng

Invigorating , treating  Invigorating , nourishing ,  Tonifying the muscle and 

collapse, reinforcing the  clearing heat and promoting  bone, diuresis to alleviate 
spleen, nourishing the lung,  the generation of the body  edema. 
promoting the production of  fluid. 
the body fluid, quenching  Mild energy booster, being 
thirst, tranquilizing the mind 
Acts on the heart, lung and  pungent for dispersing 
and improving intelligence.  kidney . clearing heat and  exopathogens, bitter and dry 
fire, as a heat‐clearing tonic  for eliminating dampness, 
Large doses of Panax Ginseng  with tonification as well as  warm for dispersing cold and 
can raise blood pressure.  purgation  tonifying liver and kidney, 
Very small doses have a mild  muscles and tendons, the 
sedative effect. Both American ginseng root  herb is suitable for 
and Panax Ginseng have the  syndromes of prolonged 
Proven to extend endurance,  effects of invigorating  cell  wind‐dampness disease, 
making it a favorite of many  energy muscular spasm, deficiency 
athletes.   of liver and kidney, asthenia 
of muscle. 
http://www.drshen.com/ginseng.htm
J Ginseng Res. Mar 2013; 37(1): 8–29
• neuroprotection to the regulation of synaptic plasticity
• regulation of neuroinflammatory processes
• regulation of neurotransmitter release
• ginsenoside produce multi-target drugs
Æ effects on neurodegenerative and other neurological
diseases.

J Ginseng Res. 2012 Oct;36(4):342-53.

• ginsenosides-mediated neuroprotective mechanisms
Æ maintaining homeostasis
Æ anti-inflammatory, anti-oxidant, anti-apoptotic,
Æ immune-stimulatory activities.
• neurotherapeutic efficacies in neurodegenerative
(Parkinson's, Alzheimer's, Huntington's disease, and
amyotrophic lateral sclerosis and multiple sclerosis).
Curr Med Chem. 2007;14(12):1371-80
• pharmacological effects of ginsenosides
Æ modulation of angiogenesis
Æ adaptogenic on CNS
Æ steroid hormone receptors as target molecules
Æ to elicit the diverse cellular and physiological act
Æ provide clues to unravel the secret of ginseng.

Acta Neurobiol Exp (Wars). 2006;66(4):369-75

• in vivo and in vitro
(antioxidant, anti-inflammatory, anti-apoptotic and
immunostimulant properties)
Æ positively affect neurodegenerative
Æ delay neuronal aging.
• animal studies
Æ counteract and attenuate factors neuronal death
J Pharmacol Sci. 2006 Mar;100(3):175-86.
• tonic to invigorate weak bodies
• restoration of homeostasis.
• in vivo and in vitro studies
Æ cardiovascular diseases, cancer, immune deficiency,
and hepatotoxicity.
Æ exert beneficial effects on aging, CNS disorders, and
neurodegenerative diseases.
• scavenging free radicals & counteracting excitotoxicity.
• typical dosage clinical trials
(ranged from 400 mg once a day for 4 months to 200 mg
twice a day for 2 to 3 months).
Adaptogenic effects
• strengthening effect and ↑ physical and mental capacity
Æ an “adaptogenic effect”
Æ nonspecific increase in resistance to the noxious
effects of physical, chemical, or biological stress.
Lloydia . 1969 ; 32 ( 1 ): 46-51

• R b1 and R g1 ginsenosides
Æ CNS stimulatory and inhibitory effects
Æ modulate neurotransmitters.
Æ Cholinergic activity
Æ mediating learning and memory processes
Sports Med . 2000 ; 29 ( 2 ): 113-133.

• increase central choline uptake

• facilitate the release of acetylcholine from hippocampal
J Altern Complement Med . 2006 ; 12 ( 2 ): 153-157
 (Centella asiatica – Pegagan)

• axonal regeneration as a nerve tonic

• increase in neurite outgrowth in human
Æ SH-SY5Y cells in the presence of nerve growth factor
• neurite elongation
Æ Asiatic acid (AA),
Æ blocked by extracellular-signal-regulated kinase (ERK)
Æ more rapid functional recovery
Æ increased axonal regeneration
Æ (larger calibre axons and greater numbers of
myelinated axons)
• axons grew at a faster rate
• accelerating repair of damaged neurons.
• crude 1.5 to 4 g/day. (500-1000 mg/day)
J Pharm Pharmacol. 2005 Sep;57(9):1221-9
Memory and Mood
• can improve cognitive function
Æ higher doses associated more correct entries
Physiol Behav . 2005;86(4):449-457.
• improved their learning behaviors
• memory retention also improved
Neuroanatomy . 2005;4:18-23.
• in vitro study
Æ 50% inhibition of acetylcholinesterase
Phytother Res . 2007;21(12):1142-1145.
Æ decreased amyloid beta plaque
Æ neurodegenerative changes
Phytother Res . 2009;23(1):14-19.
• associated with antioxidant activity
Æ ERK/RSK signaling pathway).
J Alzheimers Dis . 2008;13(3):341-349.
• increases dendritic length (intersections) and
branches of neurons of amygdala
Physiol Behav . 2005;86(4):449-457.
Phytomedicine . 2006;13(9-10):668-676.
• relieve anxiety and promote relaxation.
• animal study conducted
- gotu kola groups received either 200 or 500 mg/kg
Æ anxiolytic effects were noted
Æ not noted at the lower dose
• asiaticoside changes behavioral and anxiety measures
Æ no differences in locomotor activity
Æ does not cause sedation

J Clin Psychopharmacol. 2000;20(6):680-684.

Clinical data
• 40 healthy volunteers single oral dose 12 g (n = 20)
• or placebo (n = 20).
• acoustic startle response was reduced 60 and 90 minutes
Æ suggest a potential anxiolytic effect.
Æ no effects on self-rated mood, heart rate, or blood
Herba Hungarica 28( 1–2): 127-134.
Modern Studies
• offer support for healthy memory function.
• study in 1992 (K. Nalini) Kasturba Medical College
Æ impressive improvement in memory
Æ retention of learned behavior 3 to 60 times better
• clinical trial with mentally retarded children
Æ increase scores on intelligence
Æ even in normal children.

Phytomedicine. 2000;7:427–48.
• known to re-vitalize the brain and nervous system,
• increase attention span and concentration
• combat aging
Clin Exp Pharmacol Physiol. 2003;30:336–42.
• demonstrated cognitive-enhancing
• anti-oxidant properties
Æ evaluated in intracerebroventricular (i.c.v.)
Æ streptozotocin (STZ)-induced cognitive impairment
Æ and oxidative stress
• showed a dose-dependent ↑in cognitive behaviour
• elevated plus-maze paradigms.
• significant decrease in MDA
• an increase in glutathione and catalase levels
Æ with 200 and 300 mg/kg
oxidative stress or an impaired endogenous anti-oxidant mechanism is an
important factor as implicated in Alzheimer>s disease
The cognitive impairment was associated with free radical generation

potential efficacy of CA in preventing the cognitive deficits, as well as the

oxidative stress
J Alzheimers Dis. 2008;13:341–9.
• recent study reported
Æ phosphorylation of cyclic AMP response element
binding protein (CREB) was enhanced
Æ in both
a neuroblastoma cell line expressing amyloid
beta 1-42 (A beta) and embryonic cortical
primary cell culture

Res Commun Mol Pathol Pharmacol.2000;108:75–86

• significant neuroprotective on cultured cortical cells
• potentiation of cellular oxidative defence mechanism.
Æ efficacious protecting neurons from oxidative damage
Æ protect exposure to excess glutamate
Fitoterapia. 2003;74:431–4
• In addition
beside enhanced CREB phosphorylatioin was examined.
Æ inhibit ERK/RSK signalling pathway
(extra cellular signal-regulated kinase- ribosomal S6 kinase)
Æ mediate this effect of CA extract.
• another study
Æ 50 mg/kg/day of crude for 14 days
Æ significantly increased the anti-oxidant enzymes,
(SOD), catalase and GSHPx) in lymphoma-bearing

J Neurosci Res. 1999;58:417–25

• protective effects against beta-amyloid neurotoxicity
Æ on B103 cell cultures and hippocampal slices.
• strong inhibition of beta-amyloid- and free radical-
induced cell death.
Æ candidates for a treatment of Alzheimer’s
 (Dimethylaminoethanol)

Biochemical precursor
• related to choline
Æ biochemical precursor to neurotransmitter acetylcholine
Æ methylated to produce choline in the brain
Æ processed by the liver into choline
• bound to phospholipids in place of choline
Æ produce phosphatidyl-dimethylaminoethanol.
Æ incorporated into nerve membranes
Æ increasing fluidity and permeability,
Æ acting as an antioxidant.

. Pharmacol. Exp. Ther. 200 (3): 545–59.

Archives of gerontology and geriatrics 9 (3): 215–229.
Mechanics of Action

• DMAE is a precursor to choline

• enhance central acetylcholine formation
• crosses blood-brain barrier more easily than choline
Æ converted easily to choline
Æ increase the brain’s ability to make acetylcholine,
Æ very important neurotransmitter
Æ involved memory, learning, recall, & thought
• inhibit the oxidation of choline to betaine
Æ involved in homocysteine metabolism

Physician Desk References Health.

Dietary Supplement Information Bureau.
Biochem Pharmacol 1978, 27: 2962-2965.
• stimulate the production of choline
Æ allows brain optimize acetylcholine (Fig. 1).

Annals of the New York Academy of Sciences

2002, 959:308-320.
• involved in learning and memory.
• Professor Imre Zs.-Nagy
Æ explanation for DMAE’s effect
Æ free radical scavenger
(particular ability to protect cellular membranes);
Æ cross-linkage inhibitor;
Æ spin trapper
(a type of free radical scavenger).
Exp Gerontol 1973, 8(4): 185-191.
• Dr. Richard Hochschild proposed
Æ DMAE’s principal healthy aging mechanism
Æ acting as a “cell membrane fluidizer.”

www.raysahelian.com/dmae
• alertness and focus
- Half subjects started daily dose (6 and 12 weeks)
Æ EEG: took DMAE daily
Æ decrease in theta and alpha1 brain
Æ more alert.
Æ those on DMAE had a better mood
Æ DMAE: induce a psychophysiological state
Æ both mood and electrical pattern
• start with low dose 50 – 150 mg per day
Curr Ther Res Clin Exp . 1974;16:1238-1242.

• helpful for ADHD

• 50 children aged 6 to 12 years
• diagnosed with hyperkinesia (today likely be ADHD)
• double-blind study
• comparing DMAE to placebo.
• dose increased from 300 mg daily to 500 mg daily
Æ by the third week,
Æ continued for 10 weeks.

statistically significant test score improvements in the

treatment group compared to the placebo group
Behav Neuropsychiatry. 1974-1975;6:87-90.
• double-blind study
• compared DMAE with both methylphenidate
(Ritalin) and placebo
• 74 children having "learning disabilities" (ADHD)
• significant score improvement for both treatment
Æ over a 10-week period.
• Positive results were also seen in a small open study

Eur J Med Res. 2003

• drug action in 80 subjects.
• 6 and 12 weeks of daily intake DMAEor placebo.
Æ more active and felt better.
Æ better feeling of wellbeing
Æ mood and excite emotional disturbance.
 Patent US8207218 dmae
1. Treatment on non-dementia mild cognitive impairment
2. Aging-associated Cognitive Decline
3. Late life forgetfullness
4. Age consistent memory impairment
5. Malignant senescent forgetfulllness
6. - 89. etc

Medicinal products presented in oral form 300 mg – 3 gr

Correspond Cmax 1,5 ug/ml dimethylaminoethanol
≈ 24 ng/ml of pyroglutamic acid
PROCHOLINERGIC ACTIVITY

Improve CDR – Clinical Dementia Rating stage