Natural Brain Enhancers Nutrients That R

Natural Brain Enhancers
Nutrients hat Really Work

For Memory, Mood, And Behavior
Parris M. Kidd, PhD

Natural
Brain
Enhancers
Nutrients hat Really Work
For Memory, Mood, and Behavior
Parris M. Kidd, PhD

Every efort has been made to ensure that the information con-
tained in this book is accurate. However, the ideas contained in
this book are not intended as a substitute for consulting with your
physician.
The opinions expressed herein represent the personal views of the

author and not of the publisher.
Every efort has been made to provide accurate Internet addresses
at the time of publication, but neither the author nor the publisher
can predict which addresses may have changed since publication.
The Wellness Imperative People (TWIP)

809 Coyote Gulch
Ivins, Utah 84738
www.totalhealthmagazine.com
Copyright © 2012 by Parris M. Kidd, PhD
All rights reserved. No part of this book may be reproduced, scanned,

or distributed in any printed or electronic form, without the author’s
permission.
ISBN-13: 978-0-615-59926 -7
Interior design: Katherine Owens

Manufactured in the United States of America
ii
Contents
Contents
Technical Definitions iv
Introduction 1
Our Brain Runs On Nutrients
Chapter 1 3
DHA, The Essential Omega-3
Chapter 2 11
PS, The Most Proven Brain Booster
Chapter 3 19
GPC, The Mind-Body Nutrient
Chapter 4 25
Fully Active Folate
Chapter 5 33
SAMe (S-Adenosyl Methionine)
Chapter 6 39
Emergent Natural Brain Enhancers
Chapter 7 43
Getting Smarter All The Time
iii
Technical Definitions
Natural brain enhancer — A naturally occurring nutrient proven
to enhance human brain function in one or more clinical trials.
Plasticity — The capacity to adapt to changing circumstances by
changing function.
Cell — The most basic unit able to grow outside the body.
Brain cell — Nerve cells (“neurons”) and numerous types of other
cells that work with them to manage brain function.
Cell membrane — A very thin but continuous molecular sheet that
borders every cell and also extends into the cell interior. Carries
enzymes that manage most of the cell’s activities.
Mitochondrion — Sub-components of cells and specialized to generate
life energy. Bordered by a double membrane system.
Synapse — Connections between nerve cells and other cells that
facilitate information transfer and consolidation.
Biochemistry — The chemistry of living systems.
Metabolism — The sum total of all enzyme-related activities.
Enzyme — A catalyst that facilitates chemical reactions which
otherwise would not happen without them. Most but not all are
proteins.
Protein — A molecule produced by linking together amino acids into
a chain, which then takes on three-dimensional shape.
DNA — Deoxyribonucleic acid. The biological molecules that encodes
the amino acid sequences of proteins.
Gene — A stretch of DNA that codes for the structure of a protein.
Epigenetics — Regulation of gene activity at levels higher than the DNA.
RNA — Ribonucleic acid. Produced by DNA. Diferent forms serve
various functions to “translate” DNA into proteins.
Nutrient — A substance that can be used to support life.
Ortho nutrient — A substance that is naturally used by enzymes
in the body. First conceived by Prof. Linus Pauling, Nobel Laureate.
Nerve transmitter — A chemical made in nerve cells and released
to stimulate other cells. Sometimes called “chemical transmitter.”
Life process (function) — A linked collection of biochemical and/or
metabolic events that facilitate survival, growth, repair, or
reproduction.
iv
Introduction
Our Brain Runs On Nutrients

Our brain is what most makes us human. It is our most important
survival tool. It gives us better judgment and more sophisticated
information processing than any other beings or any computer can
achieve. This booklet is about natural brain enhancers, nutrients
that are scientiically proven to enhance the brain’s performance.
I’ve chosen only those that provide the most beneit in well-designed
clinical trials and are safe to take on a daily basis year after year.
Just within the past 20 years scientiic advances have
revolutionized understanding about the brain. Previously it was
assumed that intelligence, personality, even behavior patterns
were set in place at birth. Now researchers agree that the healthy
brain is continually modifying these functions as it adapts to
changing information coming from outside and inside the body (see
the remarkable book by Doidge in Resources, below). The term
researchers use to describe this remarkable adaptability is plasticity.
Brain plasticity explains how a person born with one side of their
brain missing can mature into an independent citizen. How a person
shot through the brain can learn to talk and walk again. Brain plasticity
suggests that with suficient hard work and opportunity almost anyone
could become a rocket scientist. But like all our other organs the brain
runs on nutrients, and to do its routine work as well as maintain
plasticity requires that it use considerable amounts of nutrients.
The human brain is very, very busy. It contains close to a trillion
highly active cells, of which the nerve cells are the body’s largest,
some approaching 4 feet in length. Each of its 100 billion nerve cells
makes (on average) more than 1000 connections with other cells.
These connections are living, dynamic structures for information
exchange and are called synapses; the healthy brain has hundreds
of trillions of them. Consequently, though the brain weighs just 2 –3
pounds it uses more than 20 percent of all the body’s energy.
These nutrient enhancers boost the brain’s performance by
improving its energy production and utilization, and by supporting
the enzymes and other proteins that manage its functions. For
each natural brain enhancer I provide a summary of its clinically
1
proven beneits (“eficacy”) and its safety. Each chapter ends with a
list of resources for further study or for referral to friends or to your
physician. Some of the more important technical terms are deined on
the page that follows the table of contents.
For the irst chapter I chose DHA, because it is so essential
for the brain irst to develop, then to mature and to maintain its
plasticity across the entire lifespan. The DHA chapter introduces the
fundamental truth that mothers and babies, children, young people,
the middle aged and the elderly all stand to beneit from consuming
suficient DHA and the other natural brain enhancer nutrients.
Chapter 2 is about PS, which works very closely with DHA in the
synapses and other zones of the brain cells. PS is abundant in breast
milk, as are DHA and GPC (the subject of Chapter 3). Beginning
well prior to birth and continuing into old age, these ortho nutrients
support and enhance the functioning of the brain’s trillions of electrical
connections. The same is true for fully active folate (Chapter 4) and
SAMe (Chapter 5).
Around the world there is an epidemic of fear about catastrophic
loss of memory associated with getting older. Yet severe memory
decline is not a natural part of aging — it isn’t inevitable, at any age.
All the nutrients covered in Chapters 1– 6 of this booklet have proven
potential to slow and possibly even reverse memory decline.
Chapter 7 will help you develop a personal brain enhancement
program to get the most out of your brain’s potential. As you read
through all the chapters, keep in mind that there is absolutely no
rule of nature, no biological program that speciies the brain must fail
anytime before age 120. These natural brain enhancers help ensure
the brain will retain its itness and plasticity across the trajectory of a
long and productive life.
Resources
1. Doidge N. “he Brain hat Changes Itself.” 2007;New York: Viking Press.
2. Pauling L. Orthomolecular psychiatry. Varying the concentrations of substances normally
present in the human body may control mental disease. Science 1968;160:265 – 71.
3. American Stroke Association, www.strokeassociation.org, accessed Feb. 11, 2012.
4. Kidd PM. Integrative management of stroke. Alternative Medicine Review 2009;14:14 – 35.
5. Alzheimer’s Association, www.alz.org, accessed Feb. 11, 2012.
6. Kidd PM. Alzheimer’s disease, amnestic mild cognitive impairment, age-associated
memory impairment: current understanding and progress toward integrative
prevention. Alternative Medicine Review 2008;13:85 –115.
2
Chapter 1. DHA
DHA, the Essential Omega-3

 Why We All Need DHA
 Essential For Life To Begin
 Deficiency Threatens Mother And Child
 Essential For The Brain At Any Age
 Powerful Support For Brain Health
 A Lifesaver For The Heart And Circulation
 More Important Than Other Omega-3s
 How To Get Enough DHA
DHA stands for DocosaHexaenoic Acid, the most important omega-3

nutrient. DHA is a fatty acid that is naturally built into our bio-
chemistry. Two-time Nobel prizewinner Linus Pauling dubbed these
“ortho” molecules, “right” nutrients for the body. Ortho nutrients
typically are extremely efective and extremely safe, and DHA its
this pattern.
Judging from its great diversity of positive actions in the brain,
DHA is currently the most important natural brain enhancer. It is
in fact important for all our organs. DHA is so important that it is
concentrated in the breast milk to support the baby’s fast-developing
vision, learning, and all other life functions.
DHA is a critically important nutrient for us all, whatever our age
or state of health. Technically, the body can make it from the simpler
omega-3 EPA (EicosaPentaenoic Acid) or possibly the even simpler ALA
(Alpha Linolenic Acid). However this capacity is extremely limited,
even in healthy people, so that DHA is practically a “dietarily essential”
nutrient—we have to get virtually all of it from our diet.
Why We All Need DHA
DHA’s fundamental importance for health comes from being a build-
ing block for the cell membrane systems that make up all our cells.
The body’s trillions of cells all are organized from cell membranes,
which are thin molecular sheets that make up the outer boundary of
the cell but also extend inside the cell, to create compartments — each
3
having specialized functions. The cell membrane networks are
packed with proteins, which are the molecular catalysts that drive
metabolism and the other processes that make up life. Each mem-
brane has a matrix, a continuous double layer of lipid molecules into
which the proteins insert. These lipid building blocks include DHA.
DHA is present in the membranes of all our cells, being an indis-
pensable membrane building block. DHA has a powerful luidizing
efect that makes the membranes semi-luid, which then allows the
membrane proteins to move about within the membrane. The proteins
must be mobile in order to carry out their necessary functions. DHA
also makes other types of chemical associations with certain of the
membrane proteins, which further adds to its nutritional importance.
Cell membranes manage most of our life processes and, as a general
rule, the more DHA in a membrane the more dynamic is that membrane
and the more it will contribute to the cell’s functional eficiency. This is
most evident in cells of the brain’s gray matter and the retina of the eye,
whose membranes carry more DHA than any others in the body.
The DHA in cell membranes also can be transformed into a
variety of smaller “messenger” molecules that difuse out of the
membrane to help coordinate important life processes. These
“docosanoids” (protectins, resolvins, maresins, and others) have
numerous regulatory efects. They are generally protective, and
help in the positive management of healthy inlammation and
other healthy responses to infection, injury, or other forms of
damage. DHA and its docosanoids are involved in regulating a
broad array of important life processes.
Most DHA dietary supplements come from ish oils. The numer-
ous ish oil supplements that are commercially available have
widely difering amounts of DHA, EPA and other omega-3 fatty
acids. The research indicates that DHA is the important omega-3
fatty acid. Further, there is a potential problem: supplements that
provide more EPA than DHA are unlikely to provide DHA beneits
since EPA may negatively interfere with DHA. I will return to this
topic after I review the proven health beneits of DHA.
Essential For Life To Begin
DHA’s crucial importance begins at conception: its presence in
the sperm’s cell membrane allows this cell to swim vigorously and
4
Chapter 1. DHA
fertilize the egg. And DHA remains important all through life. Our
nutritional DHA status can be igured by measuring its level in the
blood or (better still) in the membranes of the red cells that circu-
late with the blood. Human studies have made it clear that high
red cell DHA indicates good health, and low red cell DHA indicates
increased risk for health problems.
DHA becomes ever more important as the fetal heart and brain
become organized. By the third semester of pregnancy, DHA is
becoming progressively more concentrated in the brain and in the
retina. This intensive DHA buildup continues until birth. Babies
born with poor DHA status (usually from mothers low in DHA) are
more likely to have poor sleep patterns, slower processing speed,
and visual and cognitive limitations, compared to those from moth-
ers with good DHA status.
Relative lack of DHA especially hurts infants born prema-
turely. Preemies average lower brain DHA compared to full-term
infants. They will get DHA by breast-feeding, but breast milk DHA
content depends on the mother’s DHA intake, which in the U.S.
averages quite low (below 100 mg per day). Whether her baby was
born premature or full term, if the lactating mother lacks adequate
DHA her baby has long-term risk for poor vision and for potentially
big problems with learning, self-control, mood, and other mental
functions. What’s more, low DHA intake is also bad for the mother.
Deficiency Threatens Mother And Child
All the way through pregnancy, the mother must transfer DHA to the
developing baby. After birth she continues transferring DHA to the baby
via her breast milk. This long period of passing DHA on to the child can
deplete her DHA stores unless she is supplementing them. In the days
following delivery a mother can have very low blood DHA, which then
places her at very high risk for potentially severe mood problems.
DHA deiciency also can be caused by poor lifestyle. Habitual
drinking can deplete the mother’s DHA and so can smoking (by
anyone in the household). Low DHA in the mother increases her
long-term risk for problems with mood, behavior, attention, learn-
ing, and other mental performance. The evidence is very clear:
adequate DHA intakes before and during pregnancy and lactation
are crucial for both mother and child.
5
The risks of brain problems from DHA deiciency apply to

everyone. There is substantial evidence that poor DHA intakes
increase the risks for dificulties with learning, attention and con-
centration, mood management, mood swings, self-abuse, domestic
abuse and other aggressive behavior, and for excessive negative
reactions to stress. DHA positively afects hundreds of genes
involved with managing these mental states.
Essential For The Brain At Any Age
DHA status is linked to brain performance all through life.. The clinical
evidence suggests that giving a “dificult child” DHA will likely improve
their behavior and academic performance in school. For middle-aged
people, indings from population studies suggest that the higher their
blood DHA the lower their risk for severe memory loss, as compared to
their peers with low DHA levels. For the middle aged and the elderly,
good DHA status is linked to better reaction time, sharper attention,
and better performance on tests of memory, reasoning and vocabulary.
DHA even seems to help protect against memory loss. The large
Framingham population study tracked 899 men and women begin-
ning at ages 55 – 88 years, for an average 9.1 more years. Those
with the highest DHA levels were found least likely to experience
memory loss or other cognitive decline during that period.
In 2010 a double-blind trial was conducted on 500 subjects aged
over 55 who had age-related cognitive decline, a condition that fea-
tures troublesome memory loss. Those subjects who got DHA (at
900 milligrams per day for 6 months) improved signiicantly over
those on placebo. Their learning and memory errors were reduced
by half, which the researchers judged was likely equivalent to more
than 3 years’ worth of cognitive improvement.
Powerful Support For Brain Health
Our brain is highly enriched in DHA but makes very little of it—the
liver has to produce most of the body’s DHA but may not be meeting all
the brain’s needs. A study on people with measurable memory impair-
ment found their liver DHA production impaired. The more severe
their DHA depletion, the more severe was their memory impairment.
Recent research advances prove that nutrients can have direct
efects on gene activity. This research ield is called “nutrigenomics.”
6
Chapter 1. DHA
DHA has positive gene actions in the brain that contribute to the
brain’s ongoing renewal and adaptability. Among these are:
• Natural regulator of genes that manage brain development,
maturation, and maintenance.
• Regulates genes involved with mood management, behavior,
and violence control.
• Promotes the maturation of nerve cells and their capacity to
make connections (synapses).
• Improves membrane luidity at the synapses. Much of the
DHA at the synapses is molecularly linked in with PS (Phos-
phatidylSerine), another very important brain nutrient.
• Potentiates NGF (nerve growth factor), BDNF (brain-derived
neurotrophic factor) and other growth factors that stimulate
the repair and renewal of the synapse connections and overall
circuitry in the brain.
• Elevates the activity of antioxidant protective enzymes.
• Supports genes that manage glucose transport and healthy
insulin response in the brain.
• Lowers brain beta-amyloid production, and promotes healthy
clearance of amyloid from the brain.
• Limits enzymes that can promote formation of tau tangles,
which like beta-amyloid are implicated in premature brain
decline.
A Lifesaver For The Heart And Circulation
Brain health relies on heart and circulatory health. The brain is so
active that at times it demands half or more of all the blood in cir-
culation. Virtually all the measurable indicators of cardiovascular
problems also predict brain problems to come. DHA’s premier brain
beneits likely rest on its multiple cardiovascular beneits, includ-
ing improved heart rate control, positive blood pressure efects,
better blood vessel tone, and beneits to cholesterol management.
The healthy heart is able to sensitively vary its strength and rate
of beat in response to varying demands for blood around the body. Poor
control of heartbeat is strongly linked to cardiovascular problems. In
three double-blind trials conducted with men in Australia, DHA sup-
ported healthy management of heart rate control, blood pressure, and
blood vessel tone. Tested in parallel, omega-3 EPA did not.
7
Two of these double-blind trials also examined the blood
cholesterol proile. DHA raised the levels of HDL (high-density
cholesterol), increased the HDL particle size, and also increased
the LDL particle size, all of which changes are linked to improved
cardiovascular health. Here also, EPA failed to provide any of these
beneits.
More Important Than Other Omega-3s
Whatever the type of human cell analyzed, its membranes contain
5-10 times more DHA than EPA, and traces of ALA (if any). Abnor-
mally low DHA levels in membranes predict functional problems,
but EPA and ALA levels show no correlation. And there is a real
possibility that consuming more EPA or other omega-3s than DHA
could actually block DHA’s beneits.
Currently the majority of DHA supplements are ish oil
preparations that also contain EPA in varying amounts. Careful
examination of the research reveals that consuming supplements
with more EPA than DHA tends to lower the DHA in the red cell
membranes (which match up well with DHA in the body’s other
cells). In contrast, taking DHA alone increases both DHA and EPA
in the red cell membranes.
Let me be explicit: Avoid taking ish oil supplements that pro-
vide more EPA than DHA. We really need DHA and we don’t need
anything to interfere with getting it. DHA beneits the heart and
circulation in many ways, EPA and ALA hardly at all. DHA by
itself improves memory problems, and an extensive animal study
demonstrated that DHA alone regulates hundreds of genes that
normally manage mood, behavior and healthy judgment skills in
humans.
How To Get Enough DHA
Food sources of DHA are few, especially since food plants don’t
make it. Most human populations get their DHA from ish, but
nowadays the ish stocks worldwide are contaminated with mer-
cury, PCBs, and other toxins. Taking DHA as a supplement is the
safest way to be sure you are getting enough of it.
To drive suficient DHA into our cell membranes we need sup-
plements that are much higher in DHA than in EPA—the higher
the better, but go for at least a 3 to 1 ratio of DHA to EPA. For the person
8
Chapter 1. DHA
who is basically healthy, I join other experts in suggesting 500 mg of
DHA per day. Pregnant or lactating women should take at least 1000
mg per day. Individuals with memory, mood or behavior problems, and
those with cardiovascular problems can take 1000–3000 milligrams
per day. Babies likely need at least 315 mg per day for the irst 6 months.
Children will beneit from intakes up to 1000 mg per day, or from even
higher intakes, preferably under physician supervision.
DHA is generally recognized as safe for long-term supplemen-
tation in amounts up to 3 grams (3000 milligrams) per day. Intakes
above 2000 mg per day really should be monitored by a qualiied
healthcare professional. This nutrient is so important, I strongly
recommend everyone have their red cell DHA levels tested once
every 5 –7 months. The optimal DHA level in the red cell membrane
is likely 7 and above (measured as percentage by weight of all the
red cell fatty acids). At this level DHA is likely to help manage CRP
(C-Reactive Protein), a clinical indicator of cardiovascular health.
The planet is running short of ish to make ish oil and DHA.
But squid isheries are abundant and sustainable, and the parts
not consumed for calamari are a great source of DHA. I worked
with Doctor’s Best to design Best DHA 500 From Calamari.
Each soft gelatin capsule of this sustainably harvested squid mate-
rial provides 500 mg of DHA and 50 mg of EPA.
DHA’s positive actions and clinical beneits apply all around
the body. Its awesome beneits for the brain, heart and circulation
are not matched by any other nutrient, and send the message that
this is an exceptionally important nutrient. Since it is practically
a vitamin, we all should be taking DHA every day, along with our
multivitamin-mineral supplement.
Resources
1. Pauling L. Orthomolecular psychiatry. Science 1968; 160:265 – 71.
2. Saldanha LG, others. Workshop on DHA as a required nutrient: Overview. Prostaglan-
dins, Leukotrienes and Essential Fatty Acids 2009;81:233 – 6.
3. Brenna JT, others. Alpha-linolenic acid supplementation and conversion to n-3
long-chain polyunsaturated fatty acids in humans. Prostaglandins, Leukotrienes and
Essential Fatty Acids 2009;80:85 – 91.
4. Alberts B, others. Molecular Biology of the Cell (Fourth Edition). New York: Gar-
land Science; 2002.
5. Hulbert A. Membrane fatty acids as pacemakers of animal metabolism. Lipids
2007; 42:811– 9.
6. McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and
function. Prostaglandins, Leukotrienes and Essential Fatty Acids 2006;75:329 – 49.
9
7. Woodman RJ, others. Efects of puriied eicosapentaenoic acid or docosahexaenoic

acid on platelet, ibrinolytic and vascular function in hypertensive type 2 diabetic
patients. Atherosclerosis 2003;166:85 – 93.
8. Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation.
American Journal of Clinical Nutrition 2009;89(Suppl):678S – 684S.
9. McNamara RK, others. Selective deicits in erythrocyte docosahexaenoic acid
composition in adult patients with bipolar disorder and major depressive disorder.
Journal of Afective Disorders 2010;126:303 –11.
10. Stark KD, others. Alcohol consumption in women is associated with decreased
plasma and erythrocyte docosahexaenoic acid. Alcohol in Clinical and Experimental
Research 2005;29:130– 40.
11. McNamara RK, others. Docosahexaenoic acid supplementation increases prefrontal
cortex activation during sustained attention in healthy boys. American Journal of
Clinical Nutrition 2010;91:1060 – 7.
12. Beydoun MA, others. Plasma n-3 fatty acids and the risk of cognitive decline in
older adults. American Journal of Clinical Nutrition 2007;85:1103 –11.
13. Muldoon MF, others. Serum phospholipid docosahexaenoic acid is associated with
cognitive functioning during middle adulthood. Journal of Nutrition 2010;140:848 –
53.
14. Schaefer EJ, others. Plasma phosphatidylcholine docosahexaenoic acid content and
risk of dementia and Alzheimer’s disease. he Framingham Heart Study. Archives of
Neurology 2006;63:1545 – 50.
15. Yurko-Mauro K, others. Beneicial efects of docosahexaenoic acid on cognition in
age-related cognitive decline. Alzheimer’s & Dementia 2010;6:456 – 64.
16. Astarita G, others. Deicient liver biosynthesis of docosahexaenoic acid correlates with
cognitive impairment in Alzheimer’s disease. PLoS ONE (online) 2010;5:e12538 (8
pages).
17. Cole GM, others. Dietary fatty acids and the aging brain. Nutrition Reviews
2010;68(Suppl 2):S102 –11.
18. Mori TA, others. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambula-
tory blood pressure and heart rate in humans. Hypertension 1999;34:253 – 60.
19. Mori TA, others. Diferential efects of eicosapentaenoic acid and docosahexaenoic
acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, over-
weight men. Circulation 2000;102:1264 – 69.
20. heobald HE, others. Low-dose docosahexaenoic acid lowers diastolic blood pres-
sure in middle-aged men and women. Journal of Nutrition 2007;137:973 – 8.
21. Sagara M, others. Efects of docosahexaenoic acid supplementation on blood
pressure, heart rate, and serum lipids in Scottish men with hypertension and hypercho-
lesterolemia. International Journal of Hypertension 2011;Volume 2011:7 pages.
22. Mori TA, others. Puriied eicosapentaenoic and docosahexaenoic acids have dif-
ferential efects on serum lipids and lipoproteins, LDL particle size, glucose, and
insulin in mildly hyperlipidemic men. American Journal of Clinical Nutrition
2000;71:1085 – 94.
10
Chapter 2. PS
PS, The Most Proven Brain Booster

 Proven From Double-Blind Clinical Trials
 Effective Against Early Memory Decline
 Useful For More Advanced Memory Decline
 Helps Cope With Stress, Mood Challenges
 Vital Building Block For Brain Cells
 Essential For The Brain’s Connections (Synapses)
 Supports Energy Generation By Mitochondria
 Works With DHA To Help Children And Elderly
 Functional Partner With GPC
 How To Take PS
Of all the natural brain enhancing nutrients, PS (Phosphatidyl-

Serine, fos-fa-tie-dil-ser-een) is the most proven based on clinical
trials. PS is in the phospholipid (fos-fo-lip-id) nutrient class, and
is very safe to take long-term besides being highly efective. PS
has been extensively researched at every level—some 30 double-
blind clinical trials, more than a hundred total human studies,
thousands of biochemical studies. As a dietary supplement PS
has produced beneits for people of every age group, and for a
wide variety of brain problems.
Like DHA, PS is naturally built into our biochemistry and
so it is an ortho molecule or “right” nutrient for the body. Like
DHA and most other ortho molecules, PS is extremely efective
and extremely safe. PS is more concentrated in the brain than the
other organs, which relects its special importance for our mental
functions.
PS also resembles DHA in being concentrated in the breast
milk. This is a clear sign that PS is important for the brain’s
development in childhood. PS actually is important for brain
maintenance and repair all through life.
11
Proven From Double-Blind Clinical Trials
PS has been efective in all but a very few of its double-blind clinical
trials that span a quarter century. PS is now accepted worldwide
as a dietary supplement for memory, learning and the other higher
brain functions (collectively known as cognition). PS also can help
people who have anxious or neurotic tendencies. It helps maintain
a healthy positive mood, and it assists in coping with stress.
Clinically, PS’s proven brain beneits include:
• Improvement of memory, learning and other cognitive functions
in people who are substantially impaired, compared to others in
their age group.
• Improvement of behavior, sociability (social interest) and activi-
ties of daily living, in people with major memory problems.
• Improvement of brain vitality. The brain’s energy tends to dwin-
dle when things are going wrong, and in clinical studies PS in-
creased the levels of energy in the brain tissues.
• Helpful for stress management, as tested using emotional or
physical challenges.
• Improvement of negative mood and easing of anxiety, in young
and elderly people.
• Improvement of attention and behavior in children with attention-
al and behavior problems.
• In a PET imaging study, subjects after taking PS showed improved
energy production and utilization throughout the brain.
In 2003 the U.S. Food and Drug Administration (FDA) granted
PS not just one, but two Qualiied Health Claims related to its
brain beneits. Very few nutrients have one such claim, which
requires thorough (and highly skeptical) FDA review of the
available data and is more meaningful than the usual structure-
function claim.
The qualiied health claim is not an endorsement by the FDA.
It is merely a recognition that the beneits of PS reported in sci-
entiic publications suggest it has some promise against mild or
possibly even severe memory loss. The irst allowed claim is that
PS may reduce the risk of dementia in the elderly, the second that
PS may reduce the risk of cognitive dysfunction in the elderly.
12
Chapter 2. PS
Effective Against Early Memory Decline
PS is renowned worldwide, mostly for its memory boosting efects.
The story of PS began in Italy in the 1980s, and its transition to
North America began with the work of the late Thomas Crook III,
PhD. Dr. Crook honed his skills at memory research while at the
U.S. National Institute of Mental Health (NIMH), part of the
National Institutes of Health. He pioneered “interactive test-
ing,” in which the subject uses a TV-type monitor screen. He
developed a panel of powerful but commonsense tests—name
recognition, face recognition, word and paragraph recall, writ-
ten comprehension, following a grocery list, finding keys—to
represent things that often go wrong as the brain loses func-
tion. Dr. Crook helped develop the concept of age-associated
memory impairment (AAMI).
It is normal for healthy people to experience some noticeable
loss of memory as they age. However, some individuals experi-
ence cognitive decline that is measurably worse than their peers,
although not severe enough to warrant a disease diagnosis. To be
categorized of AAMI a person must be over age 50, with cognitive
function adequate to remain productive, but with complaint of
gradual memory loss and objective evidence of memory loss on
performance tests. People with AAMI are those who score in the
bottom one-third on the performance tests. Those who score the
poorest could be at risk for major memory problems later in life.
In 1991, Dr. Crook and colleagues from Stanford and
Vanderbilt published a double-blind clinical trial of PS versus
an inactive “placebo” for AAMI. After three weeks, the PS group
demonstrated signiicant improvement over the placebo group
on memory tests, including remembering names and faces,
telephone number recall, and placement of keys and glasses.
After three months, PS had improved memory by 30 percent
compared to placebo.
A subgroup of these AAMI individuals, those who had scored
poorest prior to entering the trial, showed the most beneit from
PS. This subgroup showed improvement on both the computerized
tests and the clinical assessments. By comparing the data on
name face recall from this trial against their large database
13
from the general population, the researchers concluded that PS may
have slowed the memory decline in this subgroup by about 12 years.
Useful For More Advanced Memory Decline
PS has been used in many double-blind trials on subjects with
memory problems. It did not halt or reverse the memory loss, but
did improve some features of cognitive function.
In 1992, Dr. Crook and colleagues published a double-blind
trial with PS on people with major memory problems. Compared
to placebo, PS statistically improved 5 measures in these patients:
1. “Memory for names of familiar persons”
2. “Ability to recall the locations of frequently misplaced objects”
3. “Dificulty recalling the names of interviewer or clinic staf
members”
4. “Dificulty recalling details of events that occurred within the
past day”
5. “Dificulty recalling details of events that occurred within the
past week.”
They then did a subgroup analysis on those individuals who were
least badly alicted prior to the trial. In addition to improving
on items 3, 4 and 5 above, these individuals showed statistically
signiicant improvement from PS on:
6. “Ability to maintain concentration”
7. “Complain during interview that his/her memory is deteriorating”
8. “Appear, on the basis of the clinical interview, to sufer from
memory impairment.”
Dr. Crook and his colleagues concluded that their results from this
clinical trial and the earlier AAMI trial suggested PS could perhaps
help slow and perhaps delay the progression of memory loss.
The research by Dr. Crook and others makes clear that the
earlier a person with memory problems can get started taking PS,
the better their chance to slow, halt or possibly even reverse their
memory decline. For more advanced problems with memory, mood,
or behavior, the best approach is to use combinations of PS, DHA,
and other natural brain enhancer nutrients that will be covered in
the subsequent chapters.
14
Chapter 2. PS
Helps Cope With Stress And Mood Challenges
PS is a valuable tool against dificulties with mood management,
anxiety, and stress. In a double-blind trial with women complaining
of mood problems, PS performed signiicantly better than placebo
for improving mood and anxiety. PS also improved cognition, irrita-
bility, and sociability. In a double-blind trial with elderly men, PS
signiicantly improved their “winter blues.” These and other human
studies suggest PS can partially revitalize the aging HPA axis. HPA
stands for hypothalamic-pituitary-adrenal, the three organs most
important for managing stress and the mood and anxiety problems
often associated with stress.
In other double-blind trials, PS improved the abilities of young,
healthy subjects to cope with physical or psychological stress. One
trial involved having to do complex mental arithmetic without a
calculator, under time pressure. Another involved making an un-
rehearsed job application speech. In this trial, the subjects on PS
showed signiicantly less distress and signiicantly lower stress hor-
mones in the blood, compared to placebo.
In double-blind trials for physical performance, PS improved
golfers’ driving accuracy, as well as cycling, running, and weight
training performance. Physical challenges often raise cortisol, a
stress hormone, and PS can blunt this cortisol response. Using PS for
cortisol management may require 400 –600 mg per day, or higher
doses under physician supervision, whereas 100 –300 mg per day
will often improve memory.
Animal studies indicate PS can have a restorative efect on the
brain. Feeding PS to aging rats signiicantly slowed their expect-
ed losses of synapses and nerve cells with age. Also in aging rats,
giving PS by mouth signiicantly slowed their loss of receptors for
nerve growth factor (NGF), a protein that stimulates brain circuit
maintenance and renewal.
Vital Building Block For Brain Cells
PS is found in all cells, because its phospholipid structure is required
for building the cell membrane systems that hold cells together and
do most of their biochemical work. The membranes are very thin
but continuous molecular sheets, semi-luid yet stretchable and
strong. A membrane creates the outer border of every cell, and this
15
outer “cell membrane” is part of a membrane system that extends
into the depths of the cell.
The cell membrane system is a continuous molecular matrix
made up mainly of a double layer of phospholipids molecules, into
which protein molecules are inserted. The proteins can be partly or
totally immersed in the matrix, or clamped onto one side or other
of the membrane. The membrane matrix provides precise physical
and chemical conditions that the proteins need for optimal function.
PS is an indispensable component of this membrane matrix.
Essential For The Brain’s Connections (Synapses)
In nerve cells the outer membrane initiates and conducts electrical
signals. This membrane also propagates the signals to points
where they are transferred to other cells by way of membrane-to-
membrane connections. This nerve cell membrane relies on PS for
its electrical character. The connections are called synapses and
are the functional units of information transfer in the brain. The
healthy human brain has between 100 and 1000 trillion synapses,
all of which rely on PS for their normal functions.
Many of the membrane proteins in the synapses are receptors (mi-
cro- versions of “antennae”) that respond to chemical transmitter
substances. These transmitters are released from one cell to impact
another and make it respond. The most prominent human brain
transmitters are acetylcholine, serotonin, dopamine, epinephrine,
norepinephrine, and GABA. In animal studies PS was found to
support the various protein receptor systems in the synapses that
respond to these transmitters.
Supports Energy Generation By The Mitochondria
PS is also deeply involved in how all our cells, including the nerve
cells, make energy. They get at least 90 percent of their energy from
their mitochondria. The mitochondria are little structures inside
our cells that are fast becoming a household name. Their main job
is to generate energy for the cell to use. Every mitochondrion has
a system of double membrane that generate energy using fancy
protein assemblies packed into the membranes. For this high-
tech membrane system to work, it must have PS. Lots of PS. As
with chemical information transfer at the synapses and electrical
16
Chapter 2. PS
generation along the outer cell membranes, the membranes of the
mitochondria need PS if they are to work right.
Works With DHA To Help Children And The Elderly
Within our cells DHA is located in the membranes. Each DHA
molecule is anchored into a larger phospholipid molecule. Much
of the brain’s DHA occurs as part of PS molecules within the
membranes of nerve cells. Such PS-DHA molecules have tremendous
importance for the brain’s functions.
In the mid-90s I worked with two physicians to do three small
clinical studies with PS in children. We focused on kids having
problems with attention, learning, and behavior. PS helped these
kids, usually at doses of 200 –300 mg per day. It seemed to work even
better if the kids were also receiving DHA. Other interested parties
picked up on this inding and now make PS ingredients that contain
PS-DHA.
An ingredient containing PS-DHA was used in a double-
blind trial on children with attention and behavior problems. The
group that got PS showed more beneit than the ish oil group.
This ingredient was also used in a double-blind trial on elderly
people who had measurable memory complaints. The human
subjects signiicantly improved on one measure of memory, verbal
immediate recall. In 2010 a double-blind trial conducted in Japan
showed comparable memory beneit just from taking soy PS.
Taking PS and DHA separately as dietary supplements is less
costly and may work just as well. Many individuals are already
taking DHA supplements for reasons covered in the previous
chapter, so they can add in PS, preferably along with another
phospholipid called GPC.
Functional Partner With GPC
GPC (GlyceroPhosphoCholine) is, like PS, a phospholipid nutrient
essential to brain cell structure and function. GPC is an ortho
nutrient, like PS and DHA. But unlike PS, GPC works in the cell’s
water phase (“cytoplasm”) and not in its membrane system. GPC
also ofers beneits that nicely complement those of PS. That is why I
combined PS and GPC into one dietary supplement. GPC’s
fascinating story is the subject of the next chapter.
17
How To Take PS
The PS used in dietary supplements comes from soy. Making PS
from soy became a necessity in the 80s and 90s. The early clinical
research was done with PS produced from cow brains, but after
“mad cow” disease contaminated cattle herds around the world it
became too dangerous to use cow brains as a source of PS. Soy PS
has been proven efective in 15 double-blind clinical trials.
The most usual recommended dosage for PS is 100 –300 mg
per day, taken after meals in divided doses. The 100 mg daily dose
ofered some beneit for memory in a recent clinical trial, and doses
of 200 mg and 300 mg per day have worked in other clinical trials.
PS is very safe to take at doses up to 600 mg per day. After being
in use worldwide for more than 16 years as a dietary supplement,
PS has shown no drug interactions or other adverse efects in this
dose range.
Resources
1. Kidd PM. PS (PhosphatidylSerine), Nature’s Brain Booster. A Vital Lipid Nutrient
for Memory, Mood and Stress (Second Edition, 96 pages). 2007; Total Health Communica-
tions, St. George, Utah, USA.
2. Salem N, Niebylski CD. he nervous system has an absolute molecular species
requirement for proper function. Molecular Membrane Biology 1995;12:131– 4.
3. Kidd PM. Alzheimer’s disease, amnestic mild cognitive impairment, and age-
associated memory impairment: current understanding and progress toward integra-
tive prevention. Alternative Medicine Review 2008;13:85 – 115.
4. U.S. Food and Drug Administration. Center for Food Safety and Applied Nutrition/
Oice of Nutritional Products and Dietary Supplements. Phosphatidylserine and
cognitive dysfunction and dementia (qualiied health claim: inal decision letter).
May 13, 2003; www.fda.gov, accessed February 12, 2012.
5. Crook TH, others. Efects of phosphatidylserine in age-associated memory impair-
ment. Neurology 1991;41:644 – 9.
6. Crook TH, others. Efects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol-
ogy Bulletin 1992;28:61– 6.
7. Jaeger R, others. he efect of phosphatidylserine on golf performance. Journal of the
International Society for Sports Nutrition 2007;4:23 – 7.
8. Kato-Kataoka A, others. Soybean-derived phosphatidylserine improves memory
function of the elderly Japanese subjects with memory complaints. Journal of Clinical
Biochemistry and Nutrition 2010;47:246 – 55.
18
Chapter 3. GPC
GPC, The Mind-Body Nutrient

 Vital For Mind And Body
 Improves Function In Young, Healthy People
 Improves Brain Efficiency In Middle Age
 Slows Memory Decline In The Elderly
 Excellent Dietary Source Of Essential Choline
 Powerful Support For Active Living, Healthy Aging
GPC (GlyceroPhosphoCholine, pronounced gli-sero-fos-fo-ko-lean)

is chemically related to PS and has properties that complement
those of PS. Like PS, GPC is an ortho nutrient present in all the
cells of the body. Like PS, GPC is a phospholipid. Like PS (and
DHA), GPC is abundant in the breast milk. Unlike PS, which is
located in the cell membranes, GPC operates in the cell’s water
phase (the “cytoplasm”). GPC’s actions in the cytoplasm naturally
reinforce those of PS in the cell membranes.
Vital For Mind And Body
GPC has been widely employed as a natural brain enhancer for
decades in Europe. In 1997 I was part of the team that brought it
into North America. GPC’s beneicial actions are so diverse that
I call it “the mind-body nutrient.” GPC’s clinical beneits include:
• Sharpening of attention and memory in young healthy people.
• Enhancement of brain physiology in middle-aged people.
• Preservation of memory, learning, mood, and sociability in the elderly.
• Improvement of learning, behavior, and social skills in children.
In addition to using the actual GPC molecule, the body can transform
GPC into at least three other nutrients that have beneicial actions in
the body. These are choline, acetylcholine, and phosphatidylcholine
(fos-fa-tie-dil-ko-lean, PC). All these GPC derivatives are vitally
important for human health. Choline is practically a vitamin,
since the body can’t make it from scratch. Each GPC molecule
19
carries a molecule of choline in its structure, and taking GPC by
mouth delivers this choline into the blood. Among choline’s many
biochemical uses is its conversion by enzymes into acetylcholine,
the nerve transmitter most widely used by both brain and body.
Choline also can be converted into PC, a phospholipid crucial for
building the new cell membranes continually needed by the brain,
liver, and other organs. GPC, choline, acetylcholine, and PC feed
into numerous enzyme networks fundamental to the health of the
brain and body.
Improves Brain Function In Young, Healthy People
Two double-blind trials conducted on volunteer university students
showed that GPC can achieve a rare feat: boost performance in the
youthful brain that is already healthy and sharp. These trials were
conducted in Milan, Italy and designed on a model of “chemical
amnesia” brought on by injection with a substance called scopol-
amine.
In the irst double-blind trial, healthy men and women aged
19 –38 years were randomly chosen to receive either a GPC
supplement or a placebo, daily for a period of 10 days. Then they
reported to the clinic in Milan to be injected with scopolamine,
which typically causes a temporary amnesia that includes loss
of memory, attention and other cognitive functions for at least 6
hours. Following the scopolamine injection each subject was tested
5 times during the subsequent 6 hours. Those not injected with
scopolamine served as a control group.
The individuals who were supplemented with GPC prior to the
injection were partially protected against its amnesia efect. They
retained verbal recall, their ability to remember a series of words
read aloud to them 2–3 minutes earlier. GPC also protected their
attention capacity for the irst 3 hours past the injection. A very
interesting inding was that the control subjects who received GPC
but were not injected with scopolamine showed improved word re-
call. This inding suggested that GPC can actually improve short-
term memory in the young, healthy person.
In the second double-blind trial, the student volunteers were
pretreated with GPC for 7 days, then received the scopolamine
injection and over the following 6-hour period were tested on a
20
Chapter 3. GPC
variety of mental performance measures. GPC partially protected the
subjects’ word recall (both short-term and long-term), as well as their
capacity for abstract reasoning in the presence of distraction (also
called “working memory”). The researchers concluded that GPC’s
efect of protecting abstract reasoning was particularly important,
because this cognitive function is one of the irst to be lost during
cognitive decline.
Some of the students in this trial were pretreated not with
GPC, but with either the synthetic “brain booster” aniracetam or
the synthetic antioxidant idebenone. GPC outperformed both these
non-natural agents. In another clinical trial GPC also outperformed
another synthetic, oxiracetam. In addition to helping young, healthy
individuals, GPC also can improve brain function in the middle
aged, the elderly, even children.
Improves Brain Efficiency In Middle Age
GPC has improved the brain eficiency of over-50 subjects in
controlled clinical trials. In one double-blind trial, GPC was studied
by EEG (ElectroEncephaloGraphy) in subjects with mild memory
challenges. In EEG, a number of electrodes are positioned all
over the scalp to record the brain’s patterns of electrical activity.
Computers then analyze these patterns for signs of abnormal
brain physiology. Some of the subjects received a GPC supplement,
others received a placebo, for 3 months. At the trial’s end the GPC
subjects had an increased beta-frequency EEG band, signiicantly
better than did those on the placebo. This suggested GPC was
improving their brains to more closely resemble younger brains,
which typically have a higher beta-frequency on EEG.
In another human study GPC improved reaction time, which is
a measure of the time span (in millionths of a second) required for
the brain to perceive and respond to a speciic stimulus. Abnormally
long reaction time can indicate problems with brain function.
Slows Memory Decline In The Elderly
In various clinical trials conducted on elderly (over-65) subjects
with memory challenges, over 1,100 individuals received either
GPC or another test substance. Those who received GPC supple-
ments improved as much as 30 percent on the various cognition
21
tests. GPC consistently improved measures of memory, attention,
and mood. In some of the trials GPC also improved mental fatigue,
disorientation, irritability, emotional swings, and indiference to
surroundings.
The largest double-blind trial conducted with GPC on the elderly
included 261 subjects, followed for 6 months. GPC proved statistically
superior to the placebo, signiicantly improving not only cognition
but also behavior and activities of daily living. In 2007, the Italian
memory expert Professor Lucilla Parnetti did an in-depth review
of the published clinical trials on GPC. She concluded GPC was
efective for improving cognition, mood, and mental fatigue.
Further clinical experience with over 2,700 subjects
suggests that supplementing with GPC can help revitalize the
underperforming brain. My 2007 book “GPC, Mind-Body Nutrient”
covers these studies in detail (see Resources). In these 5 clinical
studies GPC showed no serious side efects and no abnormalities in
blood analyses and other laboratory tests. As measured by a variety
of neurologic tests, and from the collective judgment of dozens of
experienced researchers, supplementing with GPC did improve
brain alertness and overall cognitive performance in these trials.
GPC has been in use for many years in Italy, the Russian Feder-
ation, Poland, and other European countries, and in the USA since
1994. Its beneits for the human brain are consistent with its beneits
for the animal brain. In experiments with lab rats, GPC triggered
acetylcholine production in the brain, and enhanced other important
brain transmitters such as dopamine, norepinephrine, and GABA
(gamma-amino-butyric acid). When fed to old rats GPC improved
their learning and memory skills, while partially preventing the loss
of brain cells that typically occurs as they age. GPC also improved
their brain sensitivity to nerve growth factor, which is produced in
the brain to stimulate and regulate nerve cell healing processes.
Excellent Dietary Source Of Essential Choline
Choline is practically a vitamin for humans, and GPC is the best
dietary source of choline. The pure choline molecule is chemically
unstable, which may explain why foods contain very little of it. The
small amounts of choline carried in foods often are destroyed by
intestinal bacteria before they can be absorbed. Choline chloride
22
Chapter 3. GPC
and choline bitartrate, salts of choline that are commonly used in
dietary supplements typically produce just a brief rise of choline
in the blood, very little of which actually reaches the tissues.
Commonly consumed foods contain very little GPC, but taking it
as a dietary supplement steadily delivers choline into the blood for
at least 10 hours.
The body needs choline to make acetylcholine, which is the
most abundant nerve transmitter not only in the brain but in all
the other organs. It is acetylcholine that enables the nerve-muscle
synapses to stimulate our voluntary muscles to contract. Ace-
tylcholine is also the main nerve transmitter for the autonomic
nervous system, an extensive nerve network that coordinates the
non-conscious functioning of our heart and circulation, digestive
system, liver and kidneys, eyes and ears, even our reproductive
organs. Acetylcholine ties the body to the mind.
Choline also serves as a backup source of methyl groups,
which help regulate a great variety of fundamental life functions.
The profound importance of methyl for health is discussed in the
next chapter.
Powerful Support For Active Living And Healthy Aging
GPC’s primary biochemical actions support “downstream”
cascades of positive actions. For example, by supporting
acetylcholine production in the brain GPC helps sustain the
natural secretion of growth hormone from the pituitary “master”
gland into the circulating blood. A 2011 clinical report indicated
that young, healthy Japanese men showed signiicantly increased
growth hormone secretion after taking GPC.
Growth hormone is the body’s main hormone for regulating
healthy growth. Its youthful levels are already in decline by age 35 –40
years. The pituitary’s daily releases of growth hormone are naturally
triggered by nerve cells that use acetylcholine. Supplementing
with GPC provides choline to facilitate the eficient production of
acetylcholine and the healthy release of growth hormone.
In the kidneys, which are particularly vulnerable to damage
from the toxic efects of urea buildup and from cell swelling due
to osmotic pressure increase, GPC helps counteract both these
threats. In the healthy human kidney GPC reaches levels that
23
likely exceed any other nutrient except water. GPC also provides
these unique anti-urea and osmotic protective functions to the
brain, liver, and other organs.
GPC truly is a vital nutrient at all stages of life. Its unique bio-
chemical, metabolic, and protective attributes account for its con-
tributions to mind-body integration, which in turn supports active
living and healthy aging.
The Natural Brain Enhancers Product
Since GPC and PS are the two most clinically proven natural brain
enhancers, and since they functionally complement each other, I
combined them into a brain supplement called Natural Brain
Enhancers. In 2010 this product, ofered by Doctor’s Best, Inc.
of San Clemente, California won Better Nutrition magazine’s Best
Supplement award in the Brain Wellness category.
Combining GPC with PS makes Natural Brain Enhancers
a powerful dietary supplement for practically the entire spectrum
of higher brain functions, including but not limited to attention,
learning, memory, mood, behavior, and coping with stress. This
nutrient combination is also especially suited to facilitate growth
factor actions for brain circuit maintenance and renewal. Last but
not least, this award-winning supplement meets U.S. Food and Drug
Administration (FDA) guidelines as an excellent source of choline.
Resources
Alternative names for GPC include alpha-GPC, choline alfoscerate, choline alphoscerate.
1. Kidd PM. Natural Brain Enhancers. Product fact sheet. www.drbvitamins.com.
2. Kidd PM. GPC (GlyceroPhosphoCholine), Mind-Body Power for Active Living and
Healthy Aging (125 pages). 2007; Total Health Communications, St. George, Utah, USA.
3. Parnetti L, others. Cholinergic precursors in the treatment of cognitive impairment
of vascular origin. Journal of the Neurological Sciences 2007;257:264– 9.
4. Wirthensohn G, others. Role and regulation of glycerophosphorylcholine in rat
renal papilla [includes human data]. Plugers Archives 1987;409:411– 5.
5. Canal N, others. Efect of L-a-glyceryl-phosphorylcholine on amnesia caused by
scopolamine. International Journal of Clinical Pharmacology, herapy and Toxicology
1991;29:103 – 7.
6. Canal N, others. Comparison of the efects of pretreatment with choline alfoscerate,
idebenone, aniracetam and placebo on scopolamine-induced amnesia. Le Basi
Razionale della Terapia 1993;23:102 – 7.
7. Ilcol YO, others. Choline status in newborns, infants, children, breast-feeding women, breast-
fed infants and human breast milk. Journal of Nutritional Biochemistry 2005;16: 489 – 99.
8. Vega JA, others. Nerve growth factor receptor immunoreactivity in the cerebellar
cortex of aged rats: efect of choline alfoscerate treatment. Mechanisms of Ageing and
Development 1993;69:119 – 27.
24
Chapter 4. Folate
Fully Active Folate

 Vital For Numerous Life Processes
 Crucial For The Brain To Develop And Mature
 Depleted by Common Gene Variations And Lifestyle
 Promotes Healthy Mood, Memory, Behavior
 Manages Homocysteine, Supports Healthy Circulation
 Essential For Making DNA, Regulating The Genes
 A Superior Supplement Over Folic Acid
Folate is a B vitamin, and since the body cannot make it from scratch
we have to obtain it from foods or dietary supplements. Folate is
important for brain health all across the lifespan. Yet folate deiciency
is the most prevalent vitamin deiciency worldwide.
Named after the Latin word for leaf (“folium”), the folate
nutrient family covers a variety of pteroyl-glutamate substances
that are most concentrated in leafy vegetables. Foods supply
limited amounts of folates that are generally not well absorbed.
Those folates that are absorbed normally become converted into
MethylTetraHydroFolate (MTHF), mostly by the liver. MTHF is the
body’s most active folate, required by the majority of enzymes that
rely on folate, and therefore I refer to it as fully active folate.
Vital For Numerous Life Processes
MTHF is the body’s ultimate resource for methyl groups, which
are essential for a complex web of life processes. The methyl group
is chemically simple, just one carbon atom combined with three
hydrogen atoms, but it is vital for many fundamental life processes.
Over a hundred enzymes use methyl to support life processes such as:
• Production of DNA (DeoxyriboNucleic Acid), RNA (RiboNucleic
Acid) and countless other molecular components essential to
produce the enzymes and other important proteins we need. DNA
is the genetic “blueprint” for proteins, and RNA helps enzymes
translate the blueprint into the thousands of proteins that make
the cell alive.
25
• Regulation of gene activities by adding or removing methyl.
• Production of PC (PhosphatidylCholine) and other phospholipids
that are the building blocks for cell membranes.
• Production of the nerve transmitters serotonin, norepinephrine
and dopamine, and the sleep hormone melatonin.
• Recycling of homocysteine, a natural metabolic product that is
potentially toxic, into the amino acid methionine which is
relatively nontoxic.
• Wrapping of nerve cells with myelin to optimize their electrical
conduction properties.
• Numerous other processes important for healthy cell and tissue growth
and repair, and for the healthy management of cell proliferation.
Crucial For Brain Development, Maturation, Adaptability
Fully active folate is essential for the brain’s development,
maturation, and ongoing renewal thru old age. It also is crucial
for the brain’s “plasticity,” its capacity to adapt to changing life
circumstances. The brain has special protein transporters that use
energy to pump MTHF from the blood into the brain cells.
The brain’s reliance on MTHF starts at its very beginning—
in the womb. As the fetal nerve cord and then the brain become
formed at about 4 – 5 weeks after conception, MTHF from the
mother is used to produce the DNA, RNA, proteins, phospholipids,
and other biological molecules that make a functioning brain.
The brain continues to have a crucial requirement for fully
active folate from birth and across the lifespan. Fully active folate
is a key nutrient for the brain to recover from injury, and otherwise
adapt to life changes, at any age. In particular, the hippocampus
and the amygdala, those brain zones most important for memory
and learning, rely for their healthy functioning on ongoing supplies
of fully active folate.
Depleted By Common Gene Variations And Lifestyle
Poor dietary folate intake is a common cause of folate deiciency.
Smoking, excessive alcohol consumption, oral contraceptive
use, and various medications all can deplete MTHF. So also can
digestive, liver, or kidney problems. These factors also can reinforce
each other, as with smoking combined with oral contraceptive use.
26
Chapter 4. Folate
Variations in the genes that manage folate metabolism are
major contributors to folate deiciencies. It takes 4 enzymes to
fully convert the folates from foods into the fully MTHF form.
The most common variation is the C677T gene for the enzyme
MethyleneTetraHydrofolate Reductase (MTHFR). An estimated 60
percent of all Americans carry this variation, and their MTHFR
activity ranges from 30 – 65 percent of normal. The less common
1298C variation causes up to 32 percent loss of MTHFR activity.
Gene variations governing other folate converting enzymes, for
example the dihydrofolate reductase (DHFR), also can adversely
afect MTHF status. Individuals carrying these gene variations
predictably tend to have low MTHF in the blood and in the brain.
Such individuals also have higher vulnerability to lifestyle or other
factors that also deplete folates.
Promotes Healthy Mood, Memory, Behavior
Individuals deicient in MTHF are more prone to mood dificulties,
and often also have cognitive dificulties. The statistical links
between folate status and healthy mood management, and
between folate and cognitive functions, have been researched in
a number of population survey studies.
The results from several of these studies consistently showed
that the higher an individual’s folate levels, the lower their chance
for mood or cognitive dificulties. When the beneits from oral
supplementation with MTHF were compared against placebo in
controlled trials, MTHF performed markedly better than placebo.
Supplementation with MTHF signiicantly improves the likelihood
of mood beneit, the speed of beneit, and the degree of beneit, and
without serious side efects.
Researchers have suggested that MTHF promotes healthy
mood management mainly by providing methyl for the production
of serotonin, norepinephrine, and dopamine, the three chemical
transmitters most involved in determining mood. MTHF’s cognitive
beneits are likely related to its methyl support for nerve cell
replacement in the hippocampus.
The hippocampus is the brain zone most closely linked to memory
and learning, and one of just a few zones in the human brain where
27
new cells can be produced and actually become integrated into
functioning circuits. Adequate supplies of MTHF are vital to make
the DNA, RNA, proteins, phospholipids and other components for
these new cells.
A 2010 Tufts University population study surveyed 1,611
seniors (aged 60 years or over) for their blood MTHF content,
and administered a sensitive cognition test that measured
mainly information-processing speed (see the Morris reference
in Resources). They found a clear, statistically signiicant
relationship between MTHF and cognition: the higher the MTHF
blood level, the better the performance on the test. Though blood
folic acid was also measured, it showed no correlation with test
performance. The picture is clear: MTHF is absolutely required for
the brain functions that most make us human.
A Top Priority Nutrient For Healthy Pregnancy Outcome
The governments of the U.S. and many other countries recommend
that all women of childbearing age supplement with folate, especially
since their folate requirements are greatly increased during the
irst trimester and before most women become aware they are
pregnant. Women who drink, smoke or use oral contraceptives tend
to have even greater risk of folate deiciency. Lack of MTHF during
pregnancy can interfere with the healthy development of the brain,
face, mouth, spine, and other organs.
After this mandatory requirement for folate during pregnancy
became apparent, beginning in 1998 the U.S. government mandated
adding folate into foods. The choice of folic acid is unfortunate,
because MTHF is far more suitable for this purpose.
In two double-blind trials conducted with women, MTHF
supplementation raised red blood cell folate levels signiicantly
better than did folic acid supplementation. Surveys indicate that
less than half of all pregnancies in the U.S. are planned, making
it prudent for any woman who could become pregnant to consume
suficient MTHF daily.
Another nutrient that is a top priority during pregnancy is
omega-3 DHA (DocosaHexaenoic Acid), the subject of Chapter
1. A clinical study on pregnant women found that those who
supplemented with MTHF along with DHA developed higher
28
Chapter 4. Folate
levels of blood DHA than those who did not get MTHF. This inding
reinforces my strong impressions that ortho nutrients when used as
supplements tend to multiply each other’s beneits.
Manages Homocysteine, Supports Healthy Circulation
MTHF is the body’s ultimate methyl resource to keep homocysteine
(HCy) from accumulating and causing toxic damage. Homocysteine is
a normal by-product of the metabolism of methionine, an important
amino acid. However HCy is also a highly reactive, free radical-type
substance that can become toxic if allowed to accumulate. High HCy
deinitely can challenge the integrity of blood vessels, particularly
those that supply the heart and the brain.
Normally, once HCy is produced it is either transformed into
useful substances or is recycled to methionine using methyl drawn
from MTHF. But when methyl is insuficient (as in MTHF deiciency),
HCy may build up in the blood and other tissues. Predictably, when
blood MTHF becomes low, blood HCy becomes high.
Homocysteine levels frequently rise with age. In several studies
with aging subjects, including one that lasted three years, high
HCy was correlated with low MTHF status and with the health of
blood vessels that supply the brain. Supplementation with MTHF
can lower elevated HCy. A 2009 double-blind trial compared MTHF
versus folic acid (both at 400 mcg per day) for the leg circulation.
MTHF improved pulse wave velocity (PWV), a measure of arterial
health, better than did folic acid.
Essential For DNA Integrity And Epigenetic Gene Regulation
Some enzymes use methyl from MTHF to help make DNA, others
use methyl to help package the DNA into genes. A gene is a length
of DNA that has been packaged together with proteins that help
regulate their activity. Various enzymes attach or detach methyl
groups to and from the DNA or its associated proteins, as part of a
sophisticated regulatory process called epigenetics.
As the word suggests, epigenetics is higher-level gene control.
DNA is rather like genetic hardware, epigenetics more like genetic
software. Methyl is an important epigenetic tool, a kind of “toggle
switch” for turning each gene of or on. Folate deiciency creates
risks that methyl groups will be deicient and as a consequence
healthy epigenetic gene regulation will be compromised.
29
In humans lacking fully active folate, the lack of available

methyl can make DNA strands more breakable, retard normal
DNA repair, alter gene activation and even change chromosome
structure. In studies on healthy Australian adults, the efects
of mild folate deiciency on the genes were comparable to X-ray
exposure, equivalent to approximately 10 times above the maximum
X-ray limit considered safe. The one-third of the population with
the lowest folate levels showed signiicantly more of these folate
deiciency efects.
A Superior Supplement Over Folic Acid
The synthetic form of folate called folic acid is the substance
currently being used to fortify foods, and is the folate source in the
vast majority of dietary supplements. It has virtually zero value for
health unless and until it can be converted into MTHF, the body’s
fully active folate.
The enzyme tasked with converting folic acid into MTHF (DHFR,
dihydrofolate reductase) is very ineficient at this task, perhaps
because its primary action does not have to do with folic acid, which is
very rare in nature. It is estimated this enzyme probably can convert
only about 250 mcg of folic acid into MTHF each day. At least one
in three older Americans has substantial amounts of unconverted
folic acid in their circulation, and other populations such as post-
menopausal women may have even higher amounts of it.
Since folic acid fortiication began in 1998, testing of Americans has
revealed increasingly higher levels of synthetic folic acid in their blood,
not converted to MTHF. This potentially creates several problems:
1. Folic acid tends to stick very tightly onto folate enzymes, and can
block access of the natural food folates to these enzymes.
2. Folic acid in the blood can mask vitamin B12 deiciency.
3. Folic acid accumulation may inhibit the natural killer cells that
are important for healthy immunity.
4. Folic acid is not an antioxidant, unlike food folates and MTHF,
which are antioxidants. MTHF is a potent antioxidant, and
experts have suggested it helps the skin cope with “free radical”
damage from ultraviolet light. This feature by itself would strongly
recommend MTHF over folic acid for human supplementation.
30
Chapter 4. Folate
The research leaves no doubt that MTHF makes the best folate
dietary supplement.
The Best Fully Active Folate Product
I worked with Doctor’s Best, Inc. to develop the product Best Fully
Active Folate. This supplement supplies MTHF as Quatrefolic®,
namely [6S]-5-MethylTetraHydroFolic acid as its glucosamine salt.
This MTHF is human-identical, indistinguishable from the MTHF
made in the body. The glucosamine associated with this brand of
MTHF improves its long-term stability in the capsule.
The Quatrefolic MTHF in this supplement is the most stable
and best-absorbed folate form available anywhere. It is also very
afordable and suitable for vegetarians. A maintenance dose is
just one 400 microgram veggie capsule per day, taken preferably
between meals. Human studies indicate this daily intake will
signiicantly improve MTHF status regardless of genetic variations
in DHFR, MTHFR or other folate handling enzymes.
This product is also suitable for all women of childbearing age.
Pregnant women can take 2 veggie capsules per day. Individuals
with life challenges that severely deplete their MTHF stores may
do better using higher intakes, under a physician’s supervision.
Supplementing with MTHF may help dislodge folic acid that is
clinging to enzymes and may be interfering with their function.
It is likely that just about everyone can beneit from taking this
product. MTHF is the body’s ultimate methyl resource. It supplies
ample amounts of methyl for the body’s diverse needs, helps keep
potentially troublesome homocysteine at safe levels, and avoids the
myriad problems associated with consuming synthetic folic acid.
The body also uses methyl from MTHF to make the nutrient SAMe
(S-AdenosylMethionine). SAMe’s remarkable contributions to brain
health are covered in the next chapter.
Resources
1. Kidd PM. Best Fully Active Folate. Product fact sheet. www.drbvitamins.com.
2. Morris MS, others. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate
in relation to anemia, macrocytosis, and cognitive test performance in American
seniors. American Journal of Clinical Nutrition 2010;91:1733 – 44.
3. Bailey SW, others. Unmetabolized serum folic acid and its relation to folic acid
intake from diet and supplements in a nationally representative of adults aged > or
=60 y in the United States. American Journal of Clinical Nutrition 2010;92:383–89.
31
4. Troen AM, others. Unmetabolized folic acid in plasma is associated with reduced
natural killer cell cytotoxicity among postmenopausal women. Journal of Nutrition
2006;136:189 – 94.
5. Bailey SW, Ayling JE. he extremely slow and variable activity of dihydrofolate reductase
in human liver and its implications for high folic acid intake. Proceedings of the
National Academy of Sciences of the US 2009;106:15424 – 29.
6. Brown KS, others. he 5,10-methylenetetrahydrofolate reductase C677T
polymorphism interacts with smoking to increase homocysteine. Atherosclerosis
2004;174:315 – 22.
7. Greenberg JA, others. Folic acid supplementation and pregnancy: more than just
neural tube defect prevention. Reviews of Obstetretics and Gynecology 2011;4:52 – 9.
8. Rampersaud GC, others. Genomic DNA methylation decreases in response to
moderate folate depletion in elderly women. American Journal of Clinical Nutrition
2000;72:998 – 1003.
9. Everson RB, others. Association of marginal folate depletion with increased
human chromosomal damage in vivo. Journal of the National Cancer Institute
1988;80:525 – 9.
10. Ramos MI, others. Low folate status is associated with impaired cognitive function and
dementia in the Sacramento Area Latino Study on Aging. American Journal of Clinical
Nutrition 2005;82:1346–52.
11. Ginsberg LD, others. L-methylfolate plus SSRI or SNRI from treatment initiation
compared to SSRI or SNRI monotherapy in a major depressive episode. Clinical
Neuroscience 2011;8:19–28.
12. Lamers Y, others. Red blood cell folate concentrations increase more after
supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women
of childbearing age. American Journal of Clinical Nutrition 2006;84:156 – 61.
13. Prinz-Langenohl R, others. [6S]-5-methyltetrahydrofolate increases plasma folate
more efectively than folic acid in women with the homozygous or wild-type C677T
polymorphism of methylenetetrahydrofolate reductase. British Journal of Pharmacology
2009;158:2014 – 21.
14. Krauss-Etschmann S, others. Efects of ish-oil and folate supplementation of pregnant
women on maternal and fetal plasma concentrations of docosahexaenoic acid and
eicosapentaenoic acid. American Journal of Clinical Nutrition 2007;85:1392 – 400.
15. Khandanpour N, others. Randomized clinical trial of folate supplementation in
patients with peripheral arterial disease. British Journal of Surgery 2009;96:990 – 8.
16. Lee HC, others. Association study of four polymorphisms in three folate-
related enzyme genes with non-obstructive male infertility. Human Reproduction
2006;21:3162 – 70.
17. Matsui EC, Matsui W. Higher serum folate levels are associated with a lower risk of
atopy and wheeze. Journal of Allergy and Clinical Immunology 2009;123:1253 – 59.
18. Snowdon DA, others. Serum folate and the severity of atrophy of the neocortex
in Alzheimer disease: indings from the Nun Study. American Journal of Clinical
Nutrition 2000;71:993 – 8.
32
Chapter 5. SAMe
SAMe
 Potent Promoter Of Healthy Mood
 Needed By The Mitochondria To Make Energy
 Active Methyl For Synapses, DNA, Epigenetics
 Feeds “Active Sulfur” Into Antioxidant Pathways
 Promotes Liver And Intestinal Health
 The Best SAMe Dietary Supplements
SAMe (S-Adenosyl Methionine) is an ortho nutrient and the most

intensively researched of all the natural brain enhancers. SAMe
has an extended positive record of proven beneits for the brain, as
well as for the liver, digestive system, and joints. SAMe’s exceptional
beneits are related to its very high energy content and unique
molecular structure.
The SAMe molecule gets its very high energy from ATP
(Adenosine TriPhosphate), the molecule that has been called “the
body’s energy currency.” Though the SAMe molecule is relatively
small it contains 7 diferent chemical groups endowed with very
high energy. These are termed “active groups,” and more than 100
human enzymes use these groups from SAMe to overcome energy
barriers and thereby make possible a diverse array of biochemical
transformations. Researchers have noted that “no part of the SAMe
molecule goes to waste.”
SAMe’s “active methyl” is known to contribute most to its proven
beneits, but its “active sulfur” and other active groups altogether
enable an awesome diversity of life processes in living things
ranging from the simplest to the most complex. Among these are
the enzymes that make polyamines, negatively charged molecules
that help shape the 3-dimensional structure of DNA, RNA, and
proteins, and further package them into genes and chromosomes.
SAMe has been tested as a dietary supplement in well over 40
double-blind trials. The most intensive clinical research with SAMe has
33
been on mood. For this application it has proved highly efective,
especially when used as part of a comprehensive personal program.
Potent Promoter Of Healthy Mood Management
SAMe strongly promotes healthy mood, as conirmed from at
least 18 clinical trials published over almost four decades. The
latest double-blind trial was published in 2010, in the prestigious
American Journal of Psychiatry. Its indings were so impressive that
the journal also published an editorial in praise of SAMe (see the
references to Papakostas and to Nelson in the Resources section).
The American Journal of Psychiatry editorial commented
that the degree of clinical beneit from SAMe was “clinically
meaningful” and “quite respectable,” that it was well tolerated, and
also that demonstration of this new agent for mood management
is “exciting news.” This virtual endorsement of SAMe came from
a source that would not normally be considered sympathetic to
dietary supplementation.
SAMe promotes healthy mood via several likely routes.
Some researchers believe its most important mood support
comes from providing vital active methyl to enzymes that make
serotonin, norepinephrine, and dopamine, the three major brain
transmitters involved in mood maintenance. SAMe’s active
methyl also enables enzymes to recycle these transmitters as
needed to maintain healthy nerve transmitter balance. But
SAMe also strongly supports the brain’s systems for antioxidant
defense, detoxiication, repair, and renewal.
Individuals who have mood dificulties also often have
problems with memory and other cognitive functions. In a
2010 double-blind trial, SAMe was found to support cognitive
health while promoting healthy mood. Studies indicate that
some individuals with cognitive challenges have low SAMe in
the brain. Supplementing with SAMe readily elevates its levels
in the brain.
SAMe supports many of the metabolic processes known
to sustain memory. One such is the action of acetylcholine, a
major nerve transmitter that supports the complex functions
of the hippocampus and other parts of the cortex. SAMe helps
the brain conserve choline, which is necessary for making
34
Chapter 5. SAMe
acetylcholine (as previously covered in Chapter 3). SAMe also
helps brain cells maintain acetylcholine sensitivity, by enabling
a favorable cell membrane environment for the protein receptors
that respond to acetylcholine.
SAMe is important for the brain cells to make and maintain
cell membranes. The phospholipid PC (PhosphatidylCholine)
is a major cell membrane building block whose production is
facilitated by methyl from SAMe. Some nerve cells need huge cell
membrane mass to maintain their long extensions, some as long
as four feet. These “axons” usually are insulated with myelin to
enhance their electrical conduction speed, and the production of
myelin also requires SAMe.
As the largest cells in the body, and with their highly dynamic
activity, the brain’s nerve cells need a lot of energy. The human
brain weighs just 2 – 3 pounds but uses upwards of 20 percent of all
the body’s energy. The brain cells typically have dense populations
of mitochondria. Declines in memory, mood or behavior typically
are preceded by a fallof in brain energy production linked to
mitochondrial failure. The mitochondria absolutely need SAMe to
drive biochemical processes essential to their survival.
Needed By The Mitochondria To Make Energy
Mitochondria generate over 90 percent of our life energy. They have
their own metabolic apparatus, and this requires them to produce
their own DNA, RNA, and proteins, all of which activities require
SAMe. They also have to make their own coenzyme Q10 and alpha
lipoic acid, using enzymes that also require SAMe. The mitochondria
actually have special transporter proteins that import SAMe from
the rest of the cell and into their interior.
The mitochondria also produce large quantities of free radicals
that create a big “draw” on their antioxidants and further create
demand for SAMe. As they use oxygen to “burn” nutrients from
our foods and make ATP, some of this oxygen spawns oxygen free
radicals that have potential for harm. These dangerous “sparks of
metabolism” continually threaten to overwhelm the antioxidant
defenses. Their stores of SAMe help the mitochondria replete
their alpha lipoic acid, coenzyme Q10, and glutathione lost to free
radical attack.
35
The multifaceted contributions of SAMe to the mitochondria’s

survival and functional eficiency helps explain how SAMe can enhance
energy in the whole body. In two double-blind trials, subjects with
energy complaints were signiicantly improved after taking SAMe.
Active Methyl For Synapses, DNA, Epigenetics
The brain’s existence is grounded in its hundreds of trillions of
synapses. These tiny point-to-point connections between the cells
can be formed over periods of minutes, and have estimated turnover
rates as high as 5 – 7 percent per week (in the cortex). This high
synapse turnover requires a variety of molecular building blocks,
many of which require SAMe for their production.
Besides helping to make the PC for cell membranes, SAMe’s
active methyl is needed by a variety of enzymes to make DNA,
to repair DNA as it becomes damaged, to package the DNA into
genes, to synthesize diverse proteins for assembly into synapses.
The dynamic synapses create ongoing demand for SAMe.
SAMe’s active methyl is also crucial for gene regulation.
The epigenetic enzymes use methyl groups from SAMe to switch
genes on or of. Gene switching by methyl regulates cell functions,
cooperation between diferent cell types, even the programming of
reproduction and fetal development. SAMe is the necessary source
of virtually all the methyl needed for epigenetic regulation.
Feeds “Active Sulfur” Into Key Glutathione Pathways
In addition to supplying active methyl, SAMe has at least 6
other activated chemical groups that are indispensable for our
biochemical wellness. Its active sulfur group facilitates the
production of glutathione, the ultimate antioxidant within our
cells. Glutathione gets to very high levels inside the brain cells,
protecting them against “free radical” attack while regulating
their functions.
As a major backup for the brain’s glutathione, SAMe is a pillar of
our antioxidant defenses. Glutathione is vulnerable to destruction by
free radicals generated from our normal metabolism, by toxic chemicals
coming into the brain from outside the body, even by prolonged emotional
stress. SAMe is readily converted into other biomolecules that ultimately
replenish glutathione. Most of this activity occurs in the liver.
36
Chapter 5. SAMe
Promotes Liver And Intestinal Health
The liver is the body’s workhorse organ, and relies heavily on SAMe
for its structural and functional integrity. Among its 500-plus
functions is to detoxify substances absorbed from the intestinal tract.
But this also exposes the liver to toxic damage.
The liver’s SAMe reserves can become depleted by alcohol
consumption, or by exposure to a variety of chemical toxins. Glutathione
is the major biomolecule used by the liver to defend the body against toxins
such as solvents, industrial pollutants, cigarette smoke components,
and even some pharmaceutical compounds. But these detox activities
are always in delicate balance, and the liver’s health depends on having
suficient glutathione reserves. When the liver’s glutathione becomes
depleted, SAMe is called upon to help replace it.
In three clinical trials, supplementation with SAMe protected
the liver against alcohol and other manmade toxins. Beyond its
support for liver detoxiication, SAMe supports the liver’s important
bile secretion function, as reported in two clinical trials.
SAMe also helps keep the colon healthy. The colon normally
houses bacteria that produce hydrogen sulide, which is potentially
toxic to biomolecules. The cells that line the colon use SAMe to
detoxify hydrogen sulide. In a clinical study, dificulties with colon
function were linked to low blood levels of SAMe.
Excellent Support For The Joints
SAMe’s “active sulfur” group supports the production of collagens
and proteoglycans, large molecules important for building the
connective tissues of the joints. SAMe has proven to be a premier
nutrient for joint comfort and mobility, after 14 clinical trials. One
of these trials lasted two years: SAMe progressively improved joint
health over this time period, and was very well tolerated.
The Best SAMe Dietary Supplements
SAMe has been available as a dietary supplement for some years,
but the earlier forms tended to prematurely lose their potency.
After much research and development work, excellent SAMe
supplements are now available in the form of enteric-coated tablets
packaged in blister packs. These ensure that the SAMe will survive
the stomach acid to reach the intestine, where it can be absorbed.
37
The Double Strength SAMe 400 and SAMe 200 products from
Doctor’s Best are optimized for SAMe’s S,S molecular form, the same
form that the body itself produces. It is important to take SAMe at least
one hour away from meals, and to avoid chewing or crushing the enteric-
coated tablet so that it can survive passage through the stomach.
Daily SAMe intakes up to 1600 mg may be useful, as directed
by a competent healthcare professional. Individuals with bipolar
disorder are advised to avoid SAMe supplementation as it may
aggravate the manic phase.
SAMe’s contributions to numerous life processes make it an
indispensable natural brain enhancer. It is no wonder, then, that
SAMe has been dubbed “jack of all trades and master of everything.”
Resources
1. Papakostas GI, others. S-adenosyl methionine augmentation of serotonin reuptake
inhibitors for antidepressant nonresponders with major depressive disorder: a dou-
ble-blind, randomized clinical trial. American Journal of Psychiatry 2010;167:942 – 8.
2. Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disor-
der (Editorial). American Journal of Psychiatry 2010;167:889 – 91.
3. Levkovitz Y, others. Efects of S-adenosylmethionine augmentation of serotonin-reup-
take antidepressants on cognitive symptoms of major depressive disorder. European
Psychiatry 2011; [ePub ahead of print].
4. Morrison LD, others. Brain S-adenosylmethionine levels are severely decreased in
Alzheimer’s disease. Journal of Neurochemistry 1996;67:1328 – 31.
5. Loenen WAM. S-adenosylmethionine: jack of all trades and master of everything?
Biochemical Society Transactions 2006;34:330 – 3.
6. Fontecave M, others. S-adenosylmethionine: nothing goes to waste. Trends in the
Biochemical Sciences 2004;29:243 – 9.
7. Jacobsen S, others. Oral S-adenosylmethionine in primary ibromyalgia. Double
blind clinical evaluation. Scandinavian Journal of Rheumatology 1991; 20:294 – 302.
8. Eskiocak S, Gozen AS, Yapar SB, others. Glutathione and free sulphydryl content
of seminal plasma in healthy medical students during and after exam stress. Human
Repr 2005;20:2595 – 600.
9. Cederbaum AI. Hepatoprotective efects of S-adenosyl-l-methionine against alco-
hol-and cytochrome P450 2E1-induced liver injury. World Journal of Gastroenterol-
ogy 2010;16:1366 – 76.
10. Vincenzi B, others. he role of S-adenosyl methionine in preventing FOLFOX-
induced liver toxicity. Expert Opinion in Drug Safety 2011;10:345 – 9.
11. Santini D, others. S-adenosylmethionine (AdoMet) supplementation for treatment
of chemotherapy-induced liver injury. Anticancer Research 2003;23(6D):5173 – 79.
12. Di Padova C, others. S-adenosyl-methionine antagonizes oral contraceptive-in-
duced bile cholesterol supersaturation in healthy women. American Journal of Gas-
troenterology 1984; 79:941 – 4.
13. Schmedes A, others. Low S-adenosylmethionine concentrations found in patients
with severe inlammatory bowel disease. Clinical Chemistry and Laboratory Medicine
2004;42:648 – 53.
14. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the
treatment of osteoarthritis. American Journal of Medicine 1987;83(5A):89 – 94.
38
Chapter 6. Emergent Natural Brain Enhancers
Emergent Natural Brain Enhancers

 N-AcetylCysteine (NAC), Protector And Regulator
 Carnitine (L-Carnitine), Essential For Energy
 AcetylCarnitine (ALCAR) Enables Gene Regulation
 Magnesium L-Threonate, Brain Magnesium
 Krill’s Vital Lipids Offer Unique Brain Benefits
 Astaxanthin, Protection For Healthy Aging
 Theanine (L-Theanine), Calming Brain Nutrient
The ive nutrients that I’ve covered in the previous chapters are those most
thoroughly proven to enhance the brain in clinical trials. This chapter
summarizes a number of other clinically proven natural brain enhancers,
all likely to take on greater importance after more clinical trials.
N-AcetylCysteine (NAC), Brain Protector And Regulator
NAC is the ortho nutrient best proven to sustain the body’s glutathione
stores. Glutathione is the body’s most important antitoxin, and in the brain
not only protects the cells but also regulates the functioning of numerous
important proteins. Stressors ranging from acetaminophen, through
emotional stress and pollutants, to X-rays predictably deplete glutathione
and supplementing with NAC is the best means to replenish it.
NAC has strongly supported mood stability, insight, self-care,
motivation, clarity of thought, and social interaction, in various
clinical trials. The product NAC Detox Regulators from Doctor’s
Best combines NAC with selenium and molybdenum, both of which
are essential minerals that help power detoxiication enzymes. This
supplement broadly supports the body’s sophisticated mechanisms
for disposing of natural and manmade toxins.
Carnitine (L-Carnitine), Essential For Energy
The ortho nutrient carnitine is an amino acid vital for the body to
convert fats into energy and to efectively metabolize carbohydrates.
Carnitine is almost a vitamin and is called “conditionally essential”
because it is easily depleted by common lifestyle factors and by
advancing age. Supplementing with carnitine also helps protect
against free radical toxins.
39
The Best CARNITINE ENERGY product provides this
nutrient at full potency, namely doses of 2 to 4 grams per day, to
power youthful wellbeing and healthy aging. In a double-blind
trial with healthy people aged over 100 years and complaining of
fatigue, carnitine (2 grams per day) signiicantly improved their
mental and physical fatigue as well as their cognitive functions (see
Malaguarnera in Resources). Carnitine also provides excellent
support for the heart, circulation and immune system.
AcetylCarnitine (ALCAR) Supports Brain Gene Activity
This ortho nutrient has shown great promise for support of healthy
mood in clinical trials. It has improved cognitive function in the
middle-aged and elderly, as well as attention and behavior in
children. Its acetyl group is important for epigenetic on-of gene
switching, and operates in parallel with the methyl system for
which fully active folate (Chapter 4) and SAMe (Chapter 5) are
so important. The acetyl group also contributes to acetylcholine
transmitter production (see Chapter 3).
ALCAR is important for regulating energy production by the
mitochondria, and signiicantly improves fatigue in clinical trials.
It works together with NAC to promote glutathione buildup that
protects the brain cells. It also can activate “vitagenes” that help the
nerve cells survive stressful challenges. The Best AcetylCarnitine
supplement from Doctor’s Best provides ALCAR that rapidly enters
the brain to promote repair and renewal in the nerve cells.
Magnesium L-Threonate, Special Brain Magnesium
Magnesium is an essential mineral required by over 300 enzymes.
It is vital for such basic life processes as DNA synthesis, RNA
synthesis, protein synthesis, and mitochondrial energy production.
Magnesium is also essential for muscle contraction (including
the heartbeat), for healthy insulin management, and for healthy
mood. Dietary magnesium in its various forms facilitates learning,
memory, attention, mood, and all the other brain functions.
Magnesium deiciency is widespread in North America, yet
certain magnesium supplements are not well absorbed. Best
Brain Magnesium supplies magnesium-l-threonate (MagteinTM,
a combination of magnesium with the essential amino acid
40
Chapter 6. Emergent Natural Brain Enhancers
l-threonine that eficiently transports magnesium into the brain. In
sophisticated animal studies this magnesium transporter promoted
brain synapse function better than did other forms of magnesium.
Krill’s Vital Lipids Offer Unique Brain Benefits
Krill thrive in the frigid Antarctic seas due to their ample content
of the omega-3 fatty acids DHA (DocosaHexaenoic Acid) and EPA
(EicosaPentaenoic Acid). Authentic krill oil contains a greater
range of nutrients than ish oils, and has superior beneits. This is
because the DHA and EPA of krill oil are “pre-activated” from
being naturally linked into phospholipid molecules (refer to
Chapter 2). Phospholipids are preformed building blocks for the
cell membranes that drive life processes. In ish oil, all the DHA
and EPA occurs as triglycerides, storage forms of fatty acids (“fat”)
that are less efective as dietary supplements compared to
phospholipids.
Krill oil also has astaxanthin, which ish oils lack. Astaxanthin
gives the krill oil its bright red color AND exceptional shelf life
stability, whereas ish oils are unstable and can become prematurely
rancid. I worked with Doctor’s Best to produce both Real Krill,
which is 100 percent krill oil, and Real Krill Enhanced, which
is krill oil with a large added surplus of omega-3 DHA to fully
ensure recommended omega-3 intakes. Our krill oil is sustainably
harvested from the Antarctic Krill, Euphausia superba.
In a double-blind clinical trial, krill oil produced dramatic
beneits for women with premenstrual complaints, including
signiicant improvements of irritability, negative mood, stress, and
“feelings of being overwhelmed.” Breast tenderness, joint pain,
weight gain, abdominal pain, swelling, and bloating also improved.
Those women taking ish oil reported improvements in just weight
gain and abdominal pain.
The women taking krill oil used painkillers less often and
avoided the unpleasant “relux” sensation experienced by two-
thirds of the women who took the ish oil. Authentic krill oil also
has superior beneits for healthy management of cholesterol and
triglyceride levels already within the normal range.
41
Astaxanthin, Versatile Protection For Healthy Aging
This bright red carotenoid is a powerful cell membrane antioxidant
and helps regulate healthy inlammation. It enhances mitochondrial
eficiency and therefore may counter free radical damage associated
with aging. In one trial, healthy men aged 50 – 69 who had been
complaining of forgetfulness received astaxanthin (12 mg/day) for 12
weeks. They showed improvement in reaction time, attention, and
working memory (memory tests administered with distractions).
In cultured nerve cells astaxanthin provided powerful protection
against free radicals, and down-regulated genes linked to cell death
while up-regulating genes linked to cell survival. I published an in-
depth review of astaxanthin’s diverse clinical beneits for the brain,
eyes, circulation, and healthy aging in December 2011 (see Resources).
Theanine (L-Theanine), The Calming Brain Nutrient
This non-protein amino acid is mainly responsible for the taste and
relaxing efects of green tea. Within 30 minutes of a sip it has entered
the brain, where it promotes a relaxed state without causing drowsiness.
Suntheanine® L-Theanine from Doctor’s Best is a patented,
100 percent pure theanine produced in Japan from green tea leaves.
This award-winning brand has been subjected to many clinical trials.
In a 2007 double-blind trial, a single 200 mg dose was suficient to
signiicantly ease mental stress and calm the heart rate in university
students who were challenged with complicated mental arithmetic
(no calculators allowed!). In a 2011 double-blind trial, boys aged 8 –12
with attention and behavior problems received Suntheanine at 200
mg twice daily (at breakfast or after school), or a placebo, for 6 weeks.
The boys who received Suntheanine slept signiicantly longer, and
with less motor activity during the night, than did those on placebo.
Resources
1. Kidd PM. NAC Detox Regulators. Product fact sheet. www.drbvitamins.com.
2. Malaguarnera M, others. L-carnitine treatment reduces severity of physical and
mental fatigue and increases cognitive functions in centenarians. American Journal
of Clinical Nutrition 2007;86:1738 – 44.
3. Monograph: Acetyl-l-carnitine. Alternative Medicine Review 2010;15:76 – 83.
4. Kidd PM. Real Krill and Real Krill Enhanced. Product fact sheets. www.drbvitamins.com.
5. Kidd P. Astaxanthin, cell membrane nutrient with diverse clinical beneits and anti-
aging potential. Alternative Medicine Review 2011;16:355 – 64.
6. Lyon MR, others. he efects of l-theanine (Suntheanine®) on objective sleep quality
in boys with attention deicit hyperactivity disorder (ADHD). Alternative Medicine
Review 2011;16:348 – 54.
42
Chapter 7. Getting Smarter All The Time
Getting Smarter All The Time

Everyone wants to be smarter. And you can actually become smarter, by
using natural brain enhancers as the core of your own brain enhance-
ment program. They work well on their own and even better when com-
bined, and will work best when you implement the nine other guidelines
suggested below. These guidelines for your brain enhancement program
are all solidly supported by human clinical research.
•฀Avoid฀emotional฀stress.฀Prolonged emotional stress kills brain
cells and can shrink the hippocampus, the brain’s main zone for
initiating new memories. Yoga and other calming practices can be
helpful, but for emotional stress that is dragging on for more than a
few weeks the best antidote is to eliminate its source.
•฀Meditate. Meditation is a powerful tool for reducing stress and
anxiety, and for spiritual centering, whatever your particular spiri-
tual orientation. It will also help you get more in touch with your
body and this in turn will encourage you to become more conscious-
ly motivated to make positive changes for your health.
•฀Avoid฀toxic฀chemicals. “Lifestyle” toxins such as smoking and ex-
cessive alcohol consumption place a toxic load on the brain (and body).
Toxins in the air, water, and food supply further add to the toxic burden.
Think total toxic load and how to get it to zero. Check regularly to make
sure your home, workplace, school, and other places where you spend time
are free of toxic materials (refer to Doris Rapp, MD, www.drrapp.com).
•฀Get฀a฀nutritionally฀oriented฀integrative฀physician. Seek out
an integrative (sometimes called “alternative” or “holistic”) health
practitioner trained to use nutrients. They can help you develop and
reine your personal program.
•฀Perfect฀your฀diet.฀The mainstream food supply can be treacher-
ous. Purchase organically certiied foods as much as possible. Such
foods as Alaskan sockeye salmon, free-range organic chicken, grass-
fed meats, sardines packed in water, organically grown blueberries
and other berries, pure cocoa powder, and extra virgin olive oil are
especially good “brain foods” and are just as good for the entire body.
43
•฀ Monitor฀ your฀ medications. Always request the pharmacist
provide package inserts and other relevant information about pos-
sible adverse efects and safer alternatives. One great source for
such information is Worst Pills, Best Pills (see Resources).
•฀Get฀mental฀exercise. The brain is a clear example of “use it or lose
it.” Synapses that aren’t used tend to fade away (“atrophy”). Synapses
that are suficiently stimulated produce new synapses that reinforce
the particular function. Therefore focus on reinforcing those skills and
other activities that are positive for you. If you are really concerned
about your memory, an online interactive site may be able to help. The
one I like best is www.positscience.com.
•฀Get฀physical฀exercise. This helps increase blood low to the brain,
which enhances the positive stem cell and growth factor activity that
help maintain brain plasticity. Lack of exercise is linked to brain
decline; moderate to heavy exercise lowers the risk of decline. Work
with professionals to develop an exercise program that is realistic for
your age. Aerobic and weight resistance exercise both contribute to
maintaining and improving brain health. For the elderly, and for any
age, Tai Chi or related “meditative movement” can be very helpful.
•฀ Stay฀ socially฀ engaged. Loneliness is a conirmed risk factor
for cognitive loss and other health problems. Maintain friendships
and other social relationships with people who are positive forces in
your life and do not cause you to feel stressed.
By building your own ten-point program using the natural brain en-
hancers and the other nine guidelines summarized above, you will
improve your mental performance and lower your risk of having brain
problems in the future. You can use the scientiic information in this
booklet to stay healthy and keep getting smarter for the rest of your life.
Resources
1. Merkes M. Mindfulness-based stress reduction for people with chronic diseases. Austra-
lian Journal of Primary Health 2010;16:200 – 10.
2. Gupta N, others. Efect of yoga based lifestyle intervention on state and trait anxiety.
Indian Journal of Physiology and Pharmacology 2006;50:41 – 7.
3. Kidd PM. Neurodegeneration from mitochondrial insuiciency: Nutrients, stem cells,
growth factors, and prospects for brain rebuilding using integrative management.
Alternative Medicine Review 2005;10(4): 268 – 93.
4. Worst Pills, Best Pills, www.worstpills.org, accessed February 12, 2012.
5. Jahnke R, others. A comprehensive review of health beneits of Qigong and Tai Chi.
American Journal of Health Promotion 2010; e1 – e25.
44
Dr.฀Parris฀M.฀Kidd฀earned฀his฀PhD฀in฀cell฀฀biology฀
at฀ the฀ University฀ of฀ California,฀ Berkeley.฀ He฀
began working in integrative medicine in 1983
and has concentrated on natural brain enhancers
since฀1994.฀Dr.฀Kidd฀enjoys฀educating฀the฀public฀
and physicians about brain health, and since
2008฀ has฀ been฀ working฀ with฀ Doctor’s฀ Best,฀ Inc.฀
to provide consumers with the highest quality,
clinically฀ proven฀ dietary฀ supplements.฀ Visit฀ his฀
website฀www.dockidd.com.
We at Doctor’s Best are excited to be working with

Dr. Parris Kidd to develop the safest and most effective
natural brain enhancers. As a gifted educator with a
love for science, Dr. Kidd exemplifies our philosophy of
Science Based Nutrition. Never has the need for natural
brain enhancers been greater than it is today. No one
in our industry is more qualified to develop brain
enhancing products than Dr. Kidd. All of our customers
can rest assured that Dr. Kidd will not waver in his
personal commitment to put science first as he directs
the Science team at Doctor’s Best.
Ken Halvorsrude,
President฀and฀CEO฀of฀Doctor’s฀Best,฀Inc.
USA and Canada

For more information
on the natural brain
enhancer supplements
developed with Doctor’s
Best฀by฀Dr.฀Kidd,฀visit:฀฀
www.drbvitamins.com.

Natural Brain Enhancers Nutrients That R

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Natural Brain Enhancers

Nutrients hat Really Work

Parris M. Kidd, PhD

Parris M. Kidd, PhD

The opinions expressed herein represent the personal views of the

The Wellness Imperative People (TWIP)

Copyright © 2012 by Parris M. Kidd, PhD

All rights reserved. No part of this book may be reproduced, scanned,

Interior design: Katherine Owens

Our Brain Runs On Nutrients

DHA, the Essential Omega-3

DHA stands for DocosaHexaenoic Acid, the most important omega-3

The risks of brain problems from DHA deiciency apply to

7. Woodman RJ, others. Efects of puriied eicosapentaenoic acid or docosahexaenoic

PS, The Most Proven Brain Booster

Of all the natural brain enhancing nutrients, PS (Phosphatidyl-

GPC, The Mind-Body Nutrient

GPC (GlyceroPhosphoCholine, pronounced gli-sero-fos-fo-ko-lean)

Fully Active Folate

In humans lacking fully active folate, the lack of available

SAMe (S-Adenosyl Methionine) is an ortho nutrient and the most

The multifaceted contributions of SAMe to the mitochondria’s

Emergent Natural Brain Enhancers

Getting Smarter All The Time

We at Doctor’s Best are excited to be working with

USA and Canada

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