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Microsoft word - nutrient profile revised august 06.doc

Nutrient Profile of
Nutritional Support for CNS Disorders Copyright January, 2001 Truehope Nutritional Support Ltd. A Non-Profit Company Revised August, 2006 Table of Contents

1. Nutrient Insufficiency Theory.2 2. Nutrient Profile .3 3. Possible Interfering Factors.28 4. Conclusion .32
Preface
There are many good reasons to suspect that nutrition, or the lack of it, may be the root
cause of many of our chronic illnesses, including disorders of the central nervous
system. Small population pockets in a few places around the world such as the Hunza
population in Kashmir, the Georgians from the southern Soviet Union and the mountain
village of Vilcabamba in Ecuador are reported to live much longer and remain more
vigorous in old age than in most modern societies.1 The Japanese island of Okinawa
also shares a similar reputation, and like these other populations enjoys life with little or
no chronic or mental illness. One has to ask why such a phenomenon occurs. The only
common factor shared by these diverse populations seems to be the incredible macro
and micronutrient density of their foods and water coupled with rich soils, which do not
suffer from depletion. These populations ingest many times the macro and microelement
levels ingested by the average North American.
Around the world, soil depletion of nutrients is at a very high level. The statistics from
the 1992 Earth Summit Report indicate that 85% of the minerals present in North
American topsoils 100 years ago are no longer present. This correlates with the findings
of Anne-Marie Mayer, PhD who reported that the general decline of nutrients in 40 foods
examined over a 50-year period of analysis in the UK reached a peak of an 81%
decrease for a single element.2 This decrease in nutrient density in our foods could
easily have been predicted; as for hundreds of years the principle elements replenished
in farm soils have been only nitrogen, phosphorus and potassium. The over-processing
of foods has also, no doubt, contributed to the problem of low nutrient intake. White
flour, for instance, contains only 7% of the trace elements found in whole-wheat flour.3
Another factor which figures into this equation is the load put on body resources to
metabolize and eliminate environmental contaminants and pollutants. Various chemicals
including herbicide and pesticide exposure, not to mention the numerous airborne toxins
that our bodies are constantly exposed to, put an overload on body metabolic processes
and resources to counter such exposure.
Page 1 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 1. Nutrient Insufficiency Theory

Conventional small talk about the need for dietary supplements often brings forth the
statement that our foods contain all the nutrients we require when we ensure a variety in
our diet. Though such may have been the case in the past, science will no longer
support such a concept. According to USDA recommended Dietary Guidelines for
Americans, only 25% of the overall population met the recommended calcium intake in
1994-96 and only 6% of female adults over 60 met the recommended intake of calcium.
Only 59% of the US population4 met the recommended daily iron intake for the same
period. Of even greater concern is the fact that the percentage of children meeting that
intake level was exactly the same as the general population. A majority of Americans
consume less than the minimum suggested copper intake, which is only 1.5 milligrams
per day. In addition to these statistics, even low limits of daily intake set as RDA
requirements were not met by the population in general for Vitamin E, Vitamin B6,
magnesium or zinc to mention only a few of many which could be cited.
One has but to examine the complex metabolic pathways in simple amino acid
metabolism in the body to realize that deficiency of even a single element has the
potential to wreak havoc with the complex central nervous system. Each of the hundreds
of enzymes involved in these complex pathways has a base of one of the essential
elements of life, which, as already established, may very well be lacking in our diets.
Every central nervous system disorder has been correlated with the levels of various
essential nutrients in tissues of those who suffer from the disorder. Such studies show
statistically significantly lower levels of these elements as compared to a normal control
population. Usage of several such elements to mitigate the effects of CNS disorders is
well documented in the literature. In modern time, studies of this nature, dating back to
as early as 1929, report several successful trials using the element manganese alone to
alleviate some of the symptoms of schizophrenia. Such literature is best summarized in
Dr. Melvyn R. Werback's book "Nutritional Influences on Mental Illness" – a sourcebook
of clinical research.5 He includes over 450 pages of references from hundreds of review
articles, case reports, observational studies and various types of randomized controlled
trials (with single, double blind, and cross-over designs) demonstrating efficacy with
numerous elements which have shown significant mitigating effects on symptoms of
virtually every CNS disorder.
The postulation that mental illness could be the result of something as simple as nutrient
insufficiency does not seem so outlandish after examining the evidence. In fact such a
theory would indeed explain most of what is seen in mental illness. For instance, if
mental illness is the result of deficiency, then one would expect to see a higher rate of
mental illness in those who experience uptake problems related to bowel dysfunction.
The reality of this is evidenced in an article printed in the Jan.8, 1999 issue of General
Hospital Psychiatry. According to these researchers at John Radcliffe Hospital in
Oxford, England, 90% of the patients who repeatedly sought treatment for digestive tract
symptoms but showed no evidence of organic disorder had at least one current
psychiatric diagnosis - 48% had at least two.6 Postpartum-initiated mental illness and
premenstrual syndrome are also explained by the depletion of nutrients during these
conditions. In fact, numerous situations that create a drain on the body's mineral
reserves seem to serve as a trigger point for mental illness. These would include:
accidents, surgery, situational stress and many other forms of trauma.
Page 2 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
One aspect of the literature that appears to have been overlooked (possibly due to the
scientific procedure of investigating only one variable at a time) is the probability that
many identifiable single-element deficiencies may be combining into multiple
deficiencies accompanied by more complex symptomatology. Such multiple-deficiencies
would only respond to a broad-spectrum nutritional supplement set to address virtually
every insufficiency that may play a role in symptoms. Thus one would both predict and
expect the significant positive response seen in a broad range of psychiatric symptoms
upon supplementing the very complex, highly bio-available, well-balanced supplement
we call EMPowerplus.
2. Nutrient Profile
2.1 An Introduction to EMPowerplus

EMPowerplus is an acronym, which stands for Essential Mineral Power Plus. The
supplement was developed over a five-year period following extensive research with
individuals suffering with CNS disorders. Through a process of trial and error the product
was assembled using a multivariate nutrient base. A modulation in mineral and vitamin
levels was undertaken until maximum performance of the supplement was obtained by
noting a symptoms decrease in the participants using the nutrient protocol.
EMPowerplus provides a complete and balanced nutrient program covering multiple deficiencies in numerous areas of the body including the Central Nervous System. The composite contains thirteen vitamins, three amino acids, and seventeen minerals in a highly bio-available form. Increased bio-availability allows the body to utilize a higher percentage of the mineral content making more nutrients available for the body processes. It is important to understand that minerals are involved in the human production of DNA, RNA, hormones and neurotransmitters.
2.1.1 Relationships between Nutrient deficiencies and CNS disorders
The late Linus Pauling of the Linus Pauling Heart Institute, winner of two Nobel prizes
(one in medicine) indicated "you can trace every sickness, every disease, and every
ailment to a mineral deficiency". Over 40% of the U.S. population is taking a vitamin –
mineral supplement in the hopes of finding some health benefit.7
Much research has been completed demonstrating the importance of minerals in body
function and that individuals suffering with the Central Nervous System (CNS) disorders
of ADHD, Schizophrenia, Bi-polar Disorder, Clinical Depression, Autism, Anorexia
Nervosa &
Dementia demonstrate significantly lower levels of micro and macro
elements in hair, plasma, cell, urine and tissue analysis.


ADHD
The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and
hair in 50 children aged 4 to 13 years with hyperactivity, were examined by AAS. The
average concentration of all trace elements was lower when compared with the control
group.8
Page 3 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Schizophrenia
23 hair trace elements were determined with the method of Inductively Coupled Plasma
Quantometer (ICP-AEP) in 85 cases of schizophrenics and 65 cases of normal controls.
As a whole, 17 trace elements were decreased in schizophrenics than normal controls,
the differences were significant (P less than 0.01). 9
Affective Disorders
The concentrations of a number of elements were determined in the plasma and
erythrocytes of 21 Nigerians (11 females, 10 males) with symptomatic affective
disorders. (11 depressives, 10 manics) and in 40 normal controls using proton – induced
X-ray emission (PIXE) analysis. The plasma and erythrocyte Cu, and erythrocyte P, Ca,
Fe, and Zn were significantly lower in the patients compared to the controls.10
Clinical Depression
This study investigates serum levels of zinc in 48 uni-polar depressed subjects (16
minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers. Serum
zinc levels were significantly lower in major depressed subjects than in normal
controls.11
Autism
"The concentrations of 14 elements were determined in scalp hair samples from hair
samples from control, autistic and autistic – like children. Significant differences were
noted between normal males and females for calcium, magnesium and mercury. The
autistic population had significantly lower levels of calcium, magnesium, copper,
manganese and chromium…"12

Anorexia Nervosa
"In this study, the zinc status was evaluated in 62 patients with bulimia and 24 patients
with anorexia nervosa. Forty percent of patients with bulimia and 54% of those with
anorexia nervosa had biochemical evidence of zinc deficiency.13
Dementia
"A significant decrease in both Ca and P in CSF (Cerebral Spinal Fluid) was observed in
Alzheimer's type dementia (p less than 0.01) and multi-infract dementia cases (p less
than 0.01). The geriatric controls also showed a significant decrease in both Ca and P. A
60% decrease in diffusible Ca in CSF was noted both in patients and geriatric controls
when compared to adult controls (p less than 0.05). The significant decrease in CSF Ca
and P in both groups of patients compared with age matched controls suggests this
lowering of Ca and P is not due to solely to the aging process and indicates a role in the
pathology of age – related disorders."14
Page 4 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
2.2 Ingredient List – EMPowerplus Capsules
Supplement Facts
Serving Size: 4 capsules
Servings Per Container: 57
Amount Per Serving % DV Vitamin A (retinyl palmitate) Vitamin C (ascorbic acid) Vitamin D (cholecalciferol) Vitamin E (d-alpha tocopheryl succinate) Vitamin B1 (thiamine mononitrate) Vitamin B2 (riboflavin) Vitamin B3 (niacinamide) Vitamin B5 (d-calcium pantothenate) Vitamin B6 (pyridoxine hydrochloride) Vitamin B9 ( folic acid) Vitamin B12 (cyanocobalamin) Vitamin H (biotin) Iodine (from Pacific Kelp) Proprietary Blend dl-phenylalanine, glutamine, citrus bioflavonoids, grape seed extract, choline bitartrate,
inositol, ginkgo biloba, methionine, germanium sesquioxide, boron, vanadium, nickel
* Percent Daily Values (%DV) are not established
Other Ingredients: gelatin, silicon, magnesium stearate

Page 5 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 2.3 Ingredient List – EMPowerplus Powdered Drink Mix
Supplement Facts
Serving Size: 1 scoop (1 tbsp)(16.5g) 1 scoop equals 4 capsules Servings Per Container: 60 Amount Per Serving % DV Calories from Fat Total Carbohydrates Vitamin A (betacarotene, retinyl palmitate) Vitamin C (ascorbic acid) Vitamin D (cholecalciferol) Vitamin E (d-alpha tocopheryl succinate) Vitamin B1 (thiamine mononitrate) Vitamin B2 (riboflavin) Vitamin B3 (niacinamide) Vitamin B5 (d-calcium pantothenate) Vitamin B6 (pyridoxine hydrochloride) Vitamin B9 ( folic acid) Vitamin B12 (cyanocobalamin) Vitamin H (biotin) Iodine (from Pacific Kelp) Proprietary Blend choline bitartrate, dl-phenylalanine, citrus bioflavonoids complex, glutamine, inositol,
methionine, boron citrate, grape seed extract, ginkgo biloba leaf extract, germanium
sesquioxide, vanadium, nickel sulfate.
* Percent Daily Values (%DV) are not established
Other Ingredients: whey protein (Milk), fructose, sunflower oil, milk protein, instant non
fat dry milk, acacia gum, natural flavors (banana, orange) guar gum, glycine, xanthin
gum, silicon dioxide, citric acid, stevia, magna sweet.
Page 6 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001

2.4 Detailed Analysis of EMPowerplus Including Toxicity

In this section we will explore each nutrient found in EMPowerplus and provide some of the functional and toxicity research that relates to it, and also its effect on neurochemistry. Vitamin A
The nutritionally active form of Vitamin A is Retinol. Vitamin A is converted into Retinol
and mainly stored in the liver. Of all of the sources of Vitamin A, beta-carotene is the
most available and also the form that yields the highest amount of Vitamin A. There are
many functions performed by Vitamin A, including promoting cellular growth and healing.
Vitamin A has a variety of uses in basic tissue and health maintenance, in clinical
treatment for a number of problems (some of which may be Vitamin A deficiency
symptoms), and in the prevention of many illnesses and diseases. Vitamin A works
better when there are sufficient body levels of zinc and an adequate intake of protein.
Beta-carotene may help protect the elderly from mental impairments. Research found
that in a population of males and females from 55-95 years old, increased beta-carotene
intake was associated with improved mental abilities.15
In a placebo controlled study involving 218 patients with PMS, expressed as headache,
agitation, irritation, depression and fatigue, patients received 200,000 –300,000 I.U. of
Vitamin A daily. 48% of the patients experienced complete symptom relief, 41.2% had a
partial effect, and 10.8 failed to improve.16
100 female patients were administered Vitamin A at 50,000 I.U. twice per day (100,000
I.U. total/day) during the second half of their cycles with favorable results.17
Another PMS study conducted with 30 patients using 200,000 I.U./day of Vitamin A was
administered for a period of 2-6 months. The majority of the patients considerably
improved. It was noted that the symptoms did not reoccur in the year following cessation
of the vitamin therapy.18
Vitamin A plasma level was reduced in depressive patients. In a study involving 202
healthy controls and 58 depressive patients, the depressive patients showed a
significant decrease in serum Vitamin A levels when compared to the healthy controls.19
Toxicity: Numerous studies have shown that Vitamin A is safe and has a low level of
toxicity. "Approximately 10 to 15 cases of Vitamin A toxic reactions are reported per year
in the United States, usually at doses greater than 100,000 IU/d. No adverse effects
have been reported for beta-carotene."20 A study presented in 1996 in the Archives of
Internal Medicine (an American Medical Association Journal) indicated "The mean time
to intoxication is estimated to be 7 1/2 months at doses of 300,000 IU/d and 3 1/2
months for 500,000 IU/d for 70-kg person".21 There are studies using beta-carotene
doses as high as 300,000 IU/d for over 15 years providing evidence of no adverse
effects.22
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 5,760 IU.

Page 7 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Vitamin B1 (Thiamine or Thiamin)
B1 provides support to the nervous system and mental function. It plays a role in the production of acetylcholine, an important neurotransmitter. Acetylcholine functions at the synaptic junctions of neurons. It was discovered that thiamine deficiency plays a major negative role in the CNS
disorder of anorexia nervosa.23
Thiamine has been used to successfully treat alcohol-dependent people with memory
function problems suffering with Wernicke-Korsakoff Syndrome (WKS). Treatment with
thiamine has been shown to rapidly resolve acute symptoms of the disorder.24
"In the years 1994-1997, 9 patients with no history of alcohol abuse presented with acute
signs of ophthalmoplegia or nystagmus and ataxia which resolved within 48 h after
intravenous thiamine".25
In a study of 20 patients involving biochemical evidence of thiamine deficiency related to
"junk" food diets, especially the adolescents, were impulsive, highly irritable, aggressive,
sensitive to criticism, and angered easily.26
Anxiety may be associated with a B vitamin deficiency. In 12 agoraphobic patients 7
were found to be deficient in thiamine, 6 in pyridoxine, 3 in niacin and 3 in vitamin B12.27
Toxicity: There is no stated toxic level for Vitamin B1. Consumers have taken hundreds
of milligrams per day with no reported toxic reactions.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 18 mg.


Vitamin B2 (Riboflavin)
Riboflavin acts as precursor or building block for coenzymes that relate to body energy production. It is also important in cell respiration and oxygenation. Symptoms of a deficiency in riboflavin can include dizziness, fatigue, retarded growth in children and nerve tissue damage. A recent study completed at King's College School of Medicine, London, U.K.
demonstrated that Vitamin B2 deficiency may be involved in fibromyalgia.28
In a study involving anorexic adolescent females compared to healthy adolescent
females, the anorexic patients showed lower levels of erythrocyte and plasma riboflavin
and riboflavin cofactors.29
In dementia research, deficiency of riboflavin was associated with forgetfulness, inability
to concentrate and mild confusion.30
Toxicity: An extensive literature review did not reveal any studies demonstrating toxic
reactions to the use of riboflavin. Deficiency appears to be of greater concern rather than
toxicity. Many vitamin B supplements offer riboflavin at 100mg/day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 13.5 mg.

Page 8 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Vitamin B3 (Niacin)
Niacin has been proven to be very beneficial in the treatment of CNS Disorders. It is a
precursor to the production of the coenzymes NAD (nicotinamide adenine dinucleotide)
and NADP (nicotinamide adenine dinucleotide phosphate). These two coenzymes are
important factors in brain metabolism and brain function. Deficiency in niacin and in
niacin production results in decreased production of NAD and NADP.31 This results in
metabolic deviations dependent on NAD and NADP, insufficient mitochondrial activity,32
resulting in a reduction of MAO (Monoamine Oxidase) production and followed by
inhibition of oxidative deamination of the biogenic amines, tryptamine, serotonin, ect.,
and dimethylated amines.33 34 Niacin is also a factor in the body production of the
hormones such as estrogen, progesterone, and testosterone, as well as other
corticosteroids. In human research, niacin has been proven to prevent breakage of DNA
strands.35
Deficiency in Niacin may cause emotional lability and irritability.36
ADHD is positively affected in a double blind study involving 33 children using niacin and
ascorbic acid vs. a placebo. The majority of the patients suffered with disturbed and
disturbing behavior. Only 1 out of the 33 children failed to respond positively, and all
relapsed within thirty days of cessation of the supplement program.37
Toxicity: Like the other B vitamins there seems to be no toxic dose. Upper levels of
niacin may cause a "niacin flush", a harmless reaction which may produce some
discomfort for the user. Niacin has been used in orthomolecular psychiatry in doses up
to 6000 mg/day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 90 mg.

Vitamin B5 (Pantothenic Acid)
Pantothenic acid, an antipellegra vitamin38, is part of all living cells. It plays important
roles in various metabolic processes, especially fatty acid synthesis and degradation. It
functions as Coenzyme A, which supports adrenal gland function to produce cortisone
and other adrenal hormones such as norepinephrine. It is known as the anti-stress
Vitamin And assists greatly in alleviating fatigue. B5 has been shown to have a
significant effect on human health, in combating disease.39
A study completed in an Iowa State Prison showed that deficiencies in pantothenic acid
cause irritability.40 Male volunteers were provided a diet adequate except for pantothenic
acid. The men became quarrelsome, hot tempered, and were easily upset. They also
developed low blood pressure, dizziness, extreme fatigue, muscle weakness,
sleepiness, stomach distress, constipation, rapid pulse on exertion and upper respiratory
problems.
Fatigue is also cited as an issue of deficiency in vitamin B5. 10 healthy men were placed
on a diet restrictive in vitamin B5. Five of them as well were supplemented with vitamin
B5 at 10 mg./day. After 63 days the deprived men were listless and suffered with
fatigue.41
Page 9 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Toxicity: Once again, being part of the B vitamin family, there seems to be no toxic
effects presented from relatively large doses. Doses of 1000mg/day have been used for
over six months with no ill effects.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 21.6 mg.


Vitamin B6 (Pyridoxine)
Pyridoxine is a very important B vitamin expressing itself as the coenzyme Pyridoxal –5-
phosphate. It functions in amino acid metabolism in the central nervous system. It is
responsible for the production of an important neurotransmitter, GABA (gamma –
aminobutyric acid). GABA assists in the conversion of the amino acid tryptophan to
niacin in the tryptophan pathway. A failure in the tryptophan pathway production of niacin
creates a spillover in the serotonin pathway, resulting in an excess production of
serotonin, the hallucinogen bufotin and DMT (di-methyl tryptomine).42 It is thought that
this may account for the symptom of psychosis in disorders such as schizophrenia.
Vitamin B6 also plays a key role in the synthesis of several other neurotransmitters,
including dopamine and norepinephrine.43 These neurotransmitters are significant for
human mood and emotional control.
Recent research from the Department of Pediatrics, Keio University School of Medicine,
Tokyo, Japan demonstrated that Vitamin B6 plays an integral part in the CNS as a
natural anticonvulsant. 44
Deficiency of Vitamin B6 has been proven to cause irritability in volunteers receiving a
vitamin B6 deficient diet and a pyridoxine antagonist. The participants became irritable
and depressed.45
Anxiety may be caused by deficiency of Vitamin B6. A clinical trial involving 1081 men
ages 17-29. Those found to be depleted of B6 (based on erythrocyte activity) were
significantly more anxious on the Freiburg Personality Inventory.46
Double blind autistic study. 52 Children with autism and 11 controls (normal) were
treated with Vitamin B6 and magnesium. The treatment combining both ingredients was
the most effective in reducing in autistic behavior.47

Toxicity:
Toxicity is not a major issue with Vitamin B6. There are no reports of toxic
effects using Vitamin B6. Daily doses of 150-200mg. are not uncommon.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 36 mg.

Vitamin B12 (Cyanocobalamin)
Cyanocobalamin is a vitamin that contains the mineral cobalt. B12 has been shown to be
essential in the metabolism of nerve tissue and necessary for the operation and health of
the central nervous system. B12 deficiency can be "characterized by feeding difficulties,
failure to thrive, hypotonia, seizures, microcephaly and developmental delay…often with
early death and significant neurological impairment in survivors."48 Other symptoms of
deficiency include fatigue, mental slowness, tingling, and numerous other psychological
and nerve symptoms. Cobalamin also functions in the synthesis of RNA and DNA and is
absolutely essential to proper CNS function.
Page 10 of 38
Truehope Nutritional Support Ltd., Copyright January, 2001
An interesting case was recently published involving an 11-year-old boy presenting with
severe sub-acute sensory ataxia, unusual skin hyper-pigmentation, megaloblastic
anemia, low serum B12 levels. He was diagnosed with pernicious anemia. A spinal MRI
demonstrated extensive demyelination of the posterior columns along the entire length
of the spinal cord. "Treatment with cobalamin produced complete remission of the
neurologic deficits and normalization of the MRI findings in the short space of 2 months.
Although rare, childhood pernicious anemia is a treatable disease that should be
included in the differential diagnosis of the sensory ataxias in children."49
Another case study published recently involved a "twenty-one-year-old female known to
suffer from bipolar type I disorder [who] developed features of a pseudodementia.
Following prompt initial response to treatment with antidepressants, there was an early
recurrence of cognitive impairment. Blood investigations confirmed a macrocytic
anaemia and vitamin B12 with folate deficiencies. There was dramatic resolution of
cognitive impairment after vitamin replacement."50
The following demonstrates the results of an observational study on deficiency of
Vitamin B12 in those exhibiting anxiety. In that study of young males cobalamin levels
were determined using repeated plasma measures. Those patients found to be seriously
deficit in cobalamin were also significantly more anxious on the Adjective Check List.51
In a hospitalized observational study Serum B12 was measured in every patient over 30
years old. It was estimated that the percentage of hospitalized patients with a B12 deficit
was 30 times higher that the general population for that area.52
Deficency of B12 relates to depression, confusion, mental slowness and memory
deficits. In a study of 25 patients it was shown that in all cases but two, response to B12
supplementation was significant.53
Toxicity: Vitamin B12 has been used in doses of 750-1000 mcg/day safely for fatigue
therapy. There are no reports of toxic effects from the use of B12 even with much larger
doses.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 900 mcg.

Vitamin C
Vitamin C has been proven to have a beneficial affect on cellular health. Studies have
shown that vitamin C is used by approximately 35% of the US population.54 Linus
Pauling, winner of two Nobel prizes (one in medicine), indicated that optimum levels of
vitamin C are between 2,500 and 10,000 mg per day. The scurvy that took so many lives
in the immigration of settlers to North America in early 1600-1800s was arrested by the
vitamin C found in fresh fruits and vegetables.

It appears that vitamin C deficiency may have a role in mental disorders. Plasma vitamin
C concentrations in psychiatric patients were measured in 885 patients in a psychiatric
hospital and in 110 healthy controls. The average value of vitamin C was lower in the
patients (0.51 mg/100 ml) than in the controls (0.87 mg/100 ml).55
Page 11 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
A double blind study involving 45 delinquent boys aged 16-18 at the Beaumont, Virginia
School for boys was undertaken. The treatment group was administered 1 gram each of
vitamin C and Niacin for a 6-week period. After the 6-week period the active group
showed significant improvement while the placebo group showed minor improvement.56
Nervousness may be associated with deficiency in vitamin C. Based on repeated testing
for plasma ascorbic acid levels, those found to be chronically deficient in vitamin C also
demonstrated significant symptom levels on the Adjective check list.57
In vitamin C research it was established that depression is the first clinical symptom of
scurvy or vitamin C deficiency in humans.58
Toxicity:
Toxicity of vitamin C is not an issue, given that there are so few case reports of
adverse reactions (U.S. statistics) in a population where vitamin C is used so
commonly.59 60 Vitamin C tablets are commonly produced in 500 mg and 1000 mg sizes.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 600 mg.


Vitamin D (Cholecalciferol)

Vitamin D acts as an important co-factor in the uptake and absorption of calcium and phosphorus. Calcium and phosphorus are essential to CNS function. Vitamin D has been proven to be effective in the treatment of rickets. Common sources of D vitamins are the fish oils, liver and eggs.
Calciferol (D2) when combined with calcium has been shown in research studies to
arrest the symptoms of asthma. It was concluded that calcium, given orally in
combination with calciferol (vitamin D2), causes a decrease of airway obstruction in
patients with allergic bronchial asthma. 61
Toxicity: In January of 1937 a nine-year study was presented with 64 dogs and 773
humans. In the humans, vitamin D "doses routinely given ranged upward from 200,000
I.U. total daily dose for periods ranging from 7 days to 5 years. Both human subjects
and dogs generally survived the administration of 20,000 I.U. per kilogram (14,5545,000
I.U. for 160 pound man) per day for indefinite period without intoxification." 62
Other human studies using extreme doses of vitamin D were published in medical
journals demonstrating safety. " During four three-day periods, vitamin D was given
beginning with a dose of 200,000 I.U. per day. This was increased by 200,000 I.U.
during each of the two succeeding three-day periods. During the last period, each
patient received 1,000,000 I.U. per day. None of the patients showed signs of toxicity.
During the last three days there ensued an increase in appetite and the patients had less
discomfort. There was neither loss of weight nor marked change in the clinical picture.
The blood pressure remained normal." 63
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 1,440 IU.

Page 12 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Vitamin E (Tocopherol)
Vitamin E acts as an anti-oxidant, protecting DNA, cell membranes, and enzymes from free radical damage. It has a major role in cellular health.
Research showed favorable results have been seen by patients with tardive dyskinesia
using a supplement of vitamin E.64

Toxicity: In an extensive review of available animal and human data, Bendich and
colleagues concluded that vitamin E supplementation resulted in few adverse effects,
even at doses as high as 3200 mg/day.65 Numerous studies have been also completed
using high doses of vitamin E.66 67 68 69 70 71
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 360 IU.


Vitamin B9 (Folic acid)

Folic acid is another B vitamin, and functions as a coenzyme, THFA (tetrahydrofolic
acid). Folate is commonly found in green leafy vegetables. Deficiency of folic acid is
very common and in many cases accounts for low birth weight babies. THFA is very
important to the breakdown and use of protein. It also plays a major role in the division of
cells in the body. "Folic acid plays a critical role in the prevention of chromosome
breakage and hypomethylation of DNA."72

A folate deficiency can present symptoms of cognitive impairment.73
It has been proposed that the application of folic acid in Parkinson's Disease showed
promise in replacing the current therapy of L-dopa.74

Folic acid deficiency in Bipolar disorder is not uncommon. 45 hospitalized bipolar
patients were found to have a red blood cell folate level of 193 nmol/litre compared to
the normal control group with red blood cell folate level of 896 nmol/litre.75
Folate deficiency may relate to Chronic Fatigue issues. In research based on
established norms 50% of a group of 60 CSF patients had deficient serum folate
levels.76

Toxicity:
As with the other B vitamins, there are no specific toxic reactions excessive
folate intake documented in medical literature. Deficiency is found to be of much greater
concern for health. There are studies using doses of folate as high as 60mg per day.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 1,440 mcg.
Vitamin H (Biotin)

Biotin plays a role through the biotin coenzyme in metabolizing fats. It aids in the
synthesis of fatty acids, RNA and DNA. A 1998 animal study showed a decrease in
white blood cell function with biotin deficiency.77
Page 13 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Biotin supplements may help to improve blood glucose control in diabetics by enhancing
insulin sensitivity and increasing the activity of enzymes involved in glucose
metabolism.78
Biotin in high doses may also be useful in the treatment of diabetic neuropathy.79
Biotin has also been used to treat metabolic abnormalities in sufferers of Duchenne
muscular dystrophy.80
A study was hosted wherein 4 normal subjects were feed a diet only deficient in biotin for
10 weeks. Symptoms of depression, lethargy, anorexia and fatigue were created in the
patients. All sign and symptoms were then alleviated with supplementation of biotin.81

Toxicity:
As with B vitamins, toxicity does not seem to be a problem. Most vitamin H
supplements contain about 300-400 mcg/day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 1,080 mcg.
Calcium

Calcium, one of the most abundant minerals found in the body, plays a major role in CNS function. Calcium is of great importance for all types of muscle function, including regulation of the heartbeat.
Calcium is seen as a major factor in neurotransmission and is required in the synaptic
discharge of neurotransmitters. Increased intracellular levels of calcium promote fusion
of synaptic vesicles within the axon membrane of the neuron, thereby assisting in
neurotransmission within the CNS.82 Calcium is essential for nerve impulse conduction
and activates some enzymes, which generate neurotransmitters.
Production of norepinephrine and serotonin are also affected by CNS calcium levels.
A recent double-blind, placebo-controlled study carried out at Brown University School of
Medicine evaluated the effect of calcium on PMS (premenstrual syndrome). The study
involved 466 women with PMS; calcium was effective in reducing emotional, behavioral,
and physical premenstrual symptoms.83
A study with hyperactive children compared to normal controls showed a significant
calcium deficiency in calcium levels in hair, urine, erythrocytes and plasma. Results
suggest that calcium supplementation is required in children suffering with ADHD.84
A case report of 4 autistic children who hit or poked their eyes experienced
hypocalciuria. 3 of the 4 patients ceased with the self injury when administered a calcium
supplement.85
Plasma calcium was found to be lower in observational study between 11 bipolar
patients and 10 healthy controls. 86
Serum levels of calcium were reduced significantly in 22 women with senile dementia
compared to age matched controls.87
Page 14 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
It has been shown that Vitamin D and C are required in the body uptake of calcium.

Toxicity:
Toxic effects from intake of calcium are rare, as the body can excrete excess.
Doses up to 2,500 mg/day are generally considered safe. Deficiency is an issue,
especially among women where osteoporosis, a calcium-related bone disorder, afflicts a
major percentage of women over seventy years of age. A study involving women in
France found that women supplementing with 1200 mg/day of calcium and 800 I.U.
Vitamin D/day reduced their risk of hip fractures by 23%.88
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 1,320 mg.


Phosphorous

Phosphorus is tied to calcium in bone structure and plays a significant role in CNS function. It is a part of the ATP (adenosine triphosphate) molecule, which is the body's energy carrier. Many enzymes contain as a base phosphoproteins. Phosopholipids are also involved in nerve conduction.
A 1991 study with patients with Alzheimers showed the following: "marked differences in
CSF levels of both calcium and phosphorus were observed in patients with dementia
and aged controls when compared with adult controls. A significant decrease in both Ca
and P in CSF was observed in Alzheimer's type dementia (p < 0.01) and multi-infarct
dementia cases (p < 0.01)." 89
A study involving patients with systemic lupus (1990) conducted at the University of New
Mexico reported: "Systemic lupus erythematosus (SLE) can produce profound
disturbances in the central nervous system, characterized by encephalopathy, focal
neurologic deficits, cerebral infarction, psychosis, and seizures." Ten patients with lupus
were compared to age matched normal controls. Levels of ADP, ATP, sugar
phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and
phosphodiesters in the brain tissue were examined. The study showed significant
decreases in ATP, and PCr levels were decreased to a greater extent than the ATP
levels."90
Calcium and phosphorus act together, balancing each other in many body functions.
Phosphate is the primary ion in extra- and intra-cellular fluid. It aids absorption of dietary
constituents, helps to maintain the blood at a slightly alkaline level, regulates enzyme
activity, and is involved in the transmission of nerve impulses.

Toxicity:
It is important that phosphorus and calcium are maintained in the correct
balance. An imbalance can create a calcium deficiency. The recommended upper intake
limit is set at 4000mg/day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 840 mg.

Page 15 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Magnesium

Magnesium is one of the most abundant minerals in human tissue. Magnesium is found in high concentrations inside cells, particularly those of the heart and brain. The role of magnesium continues to grow in clinical importance as evidence suggests that magnesium deficiency is active in a number of disorders. Magnesium plays a role as a co-factor in over 250 enzyme reactions. All enzymatic reactions utilizing the energy storage molecule, (ATP), adenosine triphosphate require magnesium. It is also required for DNA manufacture, protein synthesis and fatty acid synthesis Like calcium, magnesium is also involved in nerve impulse transmission. It is involved in the maintenance of the membrane electric potential and the transport across membranes of potassium, sodium, and calcium. Magnesium is necessary for the action of a compound which plays a vital role in transmitting messages from hormones and other stimuli which cause chemical reactions inside cells. Vitamin D promotes magnesium absorption. However, recent studies suggest that
calcium does not affect magnesium absorption.91
Magnesium deficiency affects body tissues. CNS symptoms of severe deficiency, include anorexia, personality changes, weakness, tiredness, vertigo, convulsions, nervousness, irritability, tremors, involuntary eye movements and irregular heartbeat. The vitamin metabolism appears to be altered in some migraine sufferers and deficiency
may contribute to symptoms through it's effects on neurotransmitters.92
Magnesium studies show that it's use may be beneficial in the treatment and prevention
of migraine. In a double blind study performed in 1996, researchers assessed the effect
of magnesium in the prevention of migraine in 81 patients aged from 18 to 65. They
were either given a placebo or magnesium supplement of 600 mg/day for 12 weeks. In
weeks 9 to 12, the migraine frequency was reduced by 42 per cent in the magnesium
group and by 16 per cent in the placebo group. The number of days with migraine and
the drug consumption for symptomatic treatment per patient also decreased significantly
in the magnesium group.93 Magnesium was also found to be useful in the treatment of
menstrual migraine.94
Magnesium deficiency may also contribute to anxiety, sleeping problems, and (CFS) chronic fatigue syndrome. Low serum levels of magnesium have also been found in patients with anorexia, bulimia and patients with irritable bowel syndrome. Chronic deficits in magnesium in children may be characterized by fidgeting, learning
difficulties, anxious restlessness, and psychomotor instability in the presence of a normal
IQ.95
In a large scale observational study, parents of autistic children provided approximately
4000 completed questionnaires providing a rating on various treatments which their
autistic children had undergone. The treatment with the highest ranking was high dosage
magnesium and B6.96
Page 16 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
In other observational studies 116 children with ADHD were studied. Levels of
magnesium were tested in serum, hair and red blood cells. A magnesium deficiency was
found in 95% of the ADHD children. There was a negative correlation between
distractibility in the ADHD children and the greater the deficiency in the magnesium.97
Blood cell concentrations of magnesium appear to be low in women with (PMS)
premenstrual syndrome. The calcium to magnesium ratio was found to be affected by
female hormone fluctuations, which affect neurotransmitter levels causing premenstrual
symptoms.98 In 1991 an Italian study demonstrated the effects in a two month long
magnesium supplementation trial on premenstrual symptoms in 32 women. Three
hundred and sixty milligrams daily at three times a day were provided from the 15th day
of the menstrual cycle to the onset of menstrual flow. The results demonstrated that
magnesium supplementation assisted greatly and was effective in the treatment of
premenstrual symptoms related to mood changes.99
Magnesium sulfate injections have been shown to improve the symptoms of chronic
fatigue syndrome.100
Toxicity: Magnesium toxicity is rare as magnesium is found within body tissue in
abundance and the body excretes excess. Clinical trials using 1080mg./day have been
proven to be safe and well below toxic values.101

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 600 mg.
Copper

Copper is essential to the formation of many genes and enzymatic factors within the human body. It is well established that the SOD1 gene (Superoxide Dismutase) which protects the human cell from oxidation and free radical damage. SOD is based on a Copper-Zinc composition. A copper containing enzyme provides a vital role in energy production in human cells. Copper is mostly concentrated in the brain and liver. Copper is necessary for the synthesis of cell membrane phospholipids, and so helps maintain myelin, the insulating sheath that surrounds nerve cells. It also helps regulate neurotransmitter levels. Copper and zinc require a proper balance of about 10:1 (zinc to copper) absorption ratio either one exceeds the balance uptake of the other becomes impaired. Research has shown that the cerebral spinal fluid in the schizophrenic shows lower than
normal levels of copper when compared to normal controls.102 Copper deficiency can
impair the function of the nervous system. This impairment causes poor concentration,
numbness and tingling, and a variety of nervous system disorders.

Copper deficiency in offenders: comparing 27 age and sex matched controls, diets of the
27 chronic juvenile offenders were low in copper.103
Copper serum levels were shown to be depressed in patients with anorexia nervosa
compared to controls.104
As an interesting side note, up to 70 percent of the copper content of flour may be lost when it is refined. Page 17 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Toxicity:
Toxicity of copper is thought to be fairly rare but high concentrations (daily
intakes of 200 mg and over) can cause effects such as nausea, vomiting, abdominal
pain, diarrhea, muscle pains, heart problems, immune suppression and abnormal mental
states. The lethal dose for copper may be as low as 3500mg.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 7.2 mg.

Iodine
Iodine has been classified as an essential trace element in human nutrition. The (WHO) World Health Organization has completed much research into the effects of the deficiency disorders stemming from lack of iodine in the human diet. The average adult body contains between 25 to 50 mg iodine, and the greater part is concentrated in the thyroid gland. The remainder is in thyroid hormones in the ovaries, blood and muscles. Iodine plays an important role in the production of the thyroid gland hormones triiodothyronine and thyroxin, which set the metabolic rate of the body. Thyroid hormones are important for development of all organs, brain growth, nerves, skin and bones. The thyroid is involved in protein manufacture, cholesterol synthesis, carbohydrate absorption and the conversion of carotene to Vitamin A. Thyroxin is an important regulator of body weight. Low levels of iodine are responsible for lower production of the thyroid hormones, in turn causing hypothyroidism a serious condition of the human endocrine system. Other symptoms of hypothyroidism include fatigue, apathy, drowsiness, sensitivity to cold, lethargy, muscle weakness, weight gain and coarse skin. Graves disease, a disorder of hyperthyroidism, is caused by an overactive thyroid. It results from a disruption in the mechanisms that control thyroid hormone function. A 1996 study demonstrated that iodine deficiency may cause learning disabilities and
poor motivation in children.105
Toxicity: The average iodine intake in the USA is over 600 mcg per day. Iodine is
rapidly absorbed from the gut. Excesses are excreted in the urine. A fatal dose is 2 to 3g
of iodine.
Toxic effects from the iodide form of iodine are rare and may include a reduction of thyroid hormone secretion, acne, and inflammation of the salivary glands when doses reach 1,500mcg.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 204 mcg.
Potassium

Potassium has many functions, and is essential for protein synthesis, conversion of blood sugar into glycogen, stimulation of the movement of the intestinal tract, and activation of many enzymes. Page 18 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Severe potassium deficiency can present symptoms of fatigue, vomiting, acute muscular weakness, paralysis, pins and needles, loss of appetite, low blood pressure, intense thirst, drowsiness, confusion and eventually coma. Muscle spasms, tetany, heart arrhythmias and muscle weakness can also be caused by increased nerve excitability associated with inadequate intake of potassium. The sudden death that can occur in fasting, anorexia nervosa or starvation is often a result of heart failure caused by potassium deficiency. Potassium supplementation has been shown to be of benefit in menopause to control mood swings and fatigue.
Toxicity: No RDA has been set in the USA but the estimated minimum requirement for
a healthy person is 2000 mg./day. Kidneys are the main regulators of body potassium
levels, maintaining blood by controlling excretion. Supplementation of potassium in
doses greater than 18,000mg may cause muscular weakness, low blood pressure,
mental confusion and eventually heart attack.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 240 mg.
Molybdenum

Since the 50's molybdenum has been considered an essential trace mineral.106 The
adult body contains about 9 mg with highest concentrations in the kidneys, liver, and
skin. It is found as a part of the enzymes, xanthine oxidase, sulfite oxidase and aldehyde
oxidase. These enzymes are responsible for the production of uric acid, a waste product
of protein metabolism; carbohydrate metabolism; iron utilization; and sulfite
detoxification.
Toxicity: Toxic effects of excess molybdenum intake include weight loss, slow growth,
anemia, diarrhea, increased blood levels of uric acid and swelling in the joints. This may
occur at intakes of 10,000 to 15,000 mcg./day. Molybdenum is conserved by the body at
low intakes but is rapidly excreted in the urine when intake is too high.107

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 144 mcg.
Zinc

Zinc is extremely important to numerous body functions. Zinc functions in over 600 enzymatic reactions in the body. It plays a key role in the synthesis and stabilization of human genes. It is necessary for cell division and the synthesis and degradation of carbohydrates, lipids and proteins, and is therefore essential for the growth and repair of tissue. Zinc deficiencies are associated with birth defects and mental impairments. Several studies have reported birth defects and pre-term deliveries in mothers with zinc Page 19 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 deficiencies during pregnancy. They have an increased risk for mental impairment, small
head size, and inter-uterine growth retardation.108
Thyroid function is affected by a deficiency of minerals in the human diet. In this study
reduced intake of both selenium and zinc lead to a 30% reduction of several thyroid
hormones.109
Zinc may play a role in calcium uptake in bone and modulate the effects of growth
hormones, and is necessary for the production of brain neurotransmitters.

Healthy liver function and release of Vitamin A from the liver both require zinc. It is
involved in the production of hydrochloric acid in the stomach and in the conversion of
fatty acids to prostaglandins, which regulate body processes such as heart rate and
blood pressure. Zinc is necessary for muscle contraction and maintaining acid-alkali
balance.
Symptoms of zinc deficiency include eczema on the face and hands, hair loss, mental
apathy, defects in the reproductive organs, delayed sexual maturation, menstrual
irregularities, decreased growth rate and impaired mental development. Deficiency may
also lead to postnatal depression, loss of the senses of taste and smell, anemia, poor
appetite, impaired conduction and nerve damage, white spots on the nails, mental
disorders, susceptibility to infections, delayed wound-healing and impotence in men.
Low levels of zinc have been found in sufferers of the eating disorder, anorexia nervosa.
And this complex disorder may be exacerbated by zinc deficiency. Initial dieting may
lead to deficiency which then reduces the senses of taste and smell, thus exacerbating
poor appetite.
The symptoms of premenstrual syndrome may be exacerbated by zinc deficiency. In a
study published in 1994, researchers at Baylor College of Medicine, Houston, Texas
assessed copper and zinc levels in ten PMS sufferers and compared these to those in
normal controls (non-suffers). Results showed lower zinc levels in the latter half of the
menstrual cycle in PMS patients.110
Studies have shown that zinc may be of benefit as part of the therapy for anorexia
nervosa. Zinc supplements have been found to increase the weight gain of anorexia
patients. Researchers involved in a 1994 Canadian randomized, double-blind, placebo-
controlled trial gave a daily dose of 100 mg of zinc or a placebo to 35 female anorexia
patients until they achieved a 10 per cent increase in body mass index (BMI). The rate of
increase in BMI of the zinc supplemented group was twice that of the placebo group.111
Zinc deficiency may be associated with mental lethargy, emotional disorders and
irritability.112
A recent Japanese study found low blood levels of zinc in people suffering from tinnitus
(ringing in the ears). Supplementation of zinc improved the condition.113
Toxicity: Studies are being conducted to see whether zinc supplementation has any
benefit in the treatment of AIDS. Some studies have shown improvement in immune
function while using zinc doses of 200 mg/day for 30days (1995 Italian AIDS study -
zinc sulfate supplements). Results showed stabilization in body weight and increases in
CD4+ lymphocytes and immune-stimulating hormone levels.
Page 20 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Toxic effects of zinc are rare as excessive absorption is usually prevented by the
abdominal pain, nausea and vomiting that very high doses (above 200 mg) cause.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 48 mg.

Chromium
Chromium is also classified as an essential trace element. Chromium has been found to be essential for body sugar metabolism and is the base of (GTF) glucose tolerance factor working with insulin it moves glucose into cells where it generates energy. The average human body should contain about 6 mg. of chromium. Symptoms of chromium deficiency include high blood fat and cholesterol levels and diabetes-like symptoms of glucose intolerance, weakness, depression, confusion, weight loss, thirst, hunger and frequent urination. Chromium tissue levels have been shown to decrease with age. British researchers in a
study published in 1997 tested for chromium levels in hair, sweat, and serum samples
obtained from over 40,000 patients.114 The results showed highly significant age-related
decreases in older people. Impairment from chromium deficiency appears to be a major
issue.
In research completed at the University of Texas it was determined by Dr. Kenneth Blume that chromium acts as an active transporter of the amino acid tryptophan in moving it across the blood-brain barrier where it is converted into serotonin. An important function of in CNS control over issues like Tourette's Syndrome, Clinical Depression and ADHD. Toxicity: Many weight loss programs are now advocating the use of chromium with
doses at 1,500 mcg/day and above.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 624 mcg.

Iron plays a significant role in oxygen transport in the body. It is the base of the hemoglobin molecule, which drives the blood oxygen activity. Enzymes involved in many metabolic functions require iron. Thyroid hormones, which regulate metabolic processes, need iron for production. It is necessary for cell division and growth through its role in DNA synthesis. It is also essential for protein metabolism. Iron also plays a role in oxygen transfer involving the production of energy in cells. Iron deficiency may be the most common nutritional deficiency in the USA. Results from the third National Health and Nutrition Examination Survey (1988-1994) suggest that iron deficiency and iron deficiency anemia are still relatively common in toddlers, adolescent girls, and women of childbearing age. Nine percent of toddlers age 1 to 2 years, and 9 percent to 11 percent of adolescent girls and women of childbearing age were iron deficient; of these, iron deficiency anemia was found in 3 percent and 2 - 5 percent respectively. These percentages correspond to approximately 700,000 toddlers and 7.8 Page 21 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 million women with iron deficiency; of these, approximately 240,000 toddlers and 3.3
million women have iron deficiency anemia. Iron deficiency occurred in around 7 percent
of older children, and those older than 50 years, and in 1 per cent of teenage boys and
young men.115
An interesting case series with two adolescents exhibiting conduct, dysthymic and
movement disorders involved iron deficiency. The case research was concluded with the
following comments: "…the weight of the evidence suggests that correcting the nutrient
deficit may be an essential step toward a refinement of therapeutic strategies."116
Iron deficiency may point to conduct problems in adolescents and children. A study of
163 patients who were incarcerated delinquents (male and females) showed a
significantly higher prevalence of iron deficiency.117
Symptoms of iron deficiency include anemia, fatigue, rapid heartbeat, breathlessness,
inability to concentrate, giddiness, disturbed sleep, severe menstrual pain and bleeding,
cracks in the corners of the mouth, eye inflammation, mouth ulcers and hair loss. Low
blood plasma levels of iron can cause generalized itching, especially in elderly people.
Compared to age and sex matched controls (176 children) the serum, urine and scalp
hair iron levels of 486 hyperactive children indicated significantly reduced levels of iron.
This suggests the need for iron supplementation in hyperactive children.118
Iron supplements may improve verbal learning and memory in those suffering with iron
deficiency. In a study published in The Lancet in 1996, researchers at Johns Hopkins
University evaluated 78 girls with non-anemic iron deficiency and measured their
cognitive ability, memory and concentration. The girls were then divided into two groups,
some were given a placebo and some were given iron supplements. After eight weeks,
measurements showed an increase in iron levels in the supplement group while the
levels in the placebo group remained low. Tests showed that the girls who took the iron
supplements performed better on the verbal learning and memory tests than the girls
who took placebo. Both groups scored the same on tests measuring their ability to pay
attention and concentrate. There was a direct relationship between how much the blood
iron levels went up and the ability to learn.119
Iron deficiencies are also cited in anorexia nervosa research.120
Toxicity: Doses of 25 to 75 mg per day have been taken without side effects, although
those with iron overload or kidney disorders might develop symptoms at lower doses.
The usual dose for treatment of deficiency is 100 mg per day in adults.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 13.74 mg.

Manganese
Manganese, an essential trace element for humans, plays an active role in CNS function. The average adult body contains between 10 and 20 mg with the highest concentrations in the bones, liver, kidneys and heart. Manganese appears to be involved in many enzyme systems, although its functions are not well understood. It acts as a co-factor for enzymes necessary for energy production and is involved in glucose metabolism, the stimulation of glycogen storage in the liver, protein digestion and Page 22 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
cholesterol and fatty acid synthesis. It is also necessary for the synthesis of DNA and
RNA.
Manganese is necessary for growth and maintenance of the nervous system. It also
plays a role in formation of blood clotting factors, female sex hormone function and
thyroid hormone function. One form of the antioxidant enzyme, superoxide dismutase,
contains manganese. Laboratory studies have shown that it can protect brain cells from
the type of damage seen in stroke and Alzheimer's disease.121
It may also help to protect against liver damage. Manganese superoxide dismutase
levels are higher in alcoholics and may help to protect against oxidative damage by
alcohol.122
Manganese supplements have also been used successfully to treat schizophrenia123,
mania and other psychoses.
Hair analysis in observational studies have shown lower than normal levels of
manganese in schizophrenic patients.124

Toxicity:
Toxic effects from oral ingestion of manganese are very rare and include
lethargy, involuntary movements, changes in muscle tone and posture.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 9.6 mg.
Selenium

Selenium was identified as an essential trace mineral for humans in the 1970s. A
selenium-based enzyme is involved in the production of thyroid hormones. Studies have
shown that thyroid hormones in elderly people are influenced by selenium status.125 In
other studies thyroid function was affected by lack of minerals. Reduced intake of both
selenium and zinc lead to a 30% reduction of several thyroid hormones.126
According to a Lancet publication in July of 2000, selenium also plays a role in CNS
mood control. In this study a deficiency was linked to adverse mood states.127
A 1996 study completed at a USDA Human Nutrition Research Center suggests that
people with low selenium levels experience depressed moods.128
Selenium is involved in maintaining liver function and protein synthesis. It also protects against toxic minerals such as arsenic, cadmium, mercury and lead. Selenium may reduce anxiety. In a Double blind trial 50 patients randomly received a
daily supplement of either 100mcg of selenium or placebo. An improvement in mood and
a decrease in anxiety was seen in the selenium group vs. the placebo group.129

Toxicity:
Selenium toxicity can occur at doses of 600 to 750 mcg. Early signs of
selenium toxicity include fatigue, irritability and dry hair.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains 204 mcg.

Page 23 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 The average adult body contains about 10mg. of nickel and it is found in body tissues. Nickel is concentrated in genetic material and is involved in protein structure and function. Deficiency in animals indicates decreased growth, dermatitis, liver damage, cell mutation and reproductive abnormalities. Low blood levels of nickel may be found in those with liver and kidney disease. Studies indicate a highly variable dietary intake of nickel, but most averages are about 0.2-0.7 mg per day.
Toxicity:
There is no stated toxicity for nickel.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Vanadium

Vanadium may act as a co-factor for enzymes involved in blood sugar metabolism, lipid and cholesterol metabolism, fertility, thyroid function, hormone production and neurotransmitter metabolism. Vanadium is mainly stored in bone & fat cells. Vanadium may be beneficial in treating subnormal thyroid function. Toxicity: There is no RDA for vanadium. In a study published in 1996, researchers at
the Albert Einstein College of Medicine in New York compared the effects of 100
mg/day of oral vanadyl sulfate
in moderately obese diabetic and nondiabetic people.
The results showed improvements in both liver and skeletal muscle insulin sensitivity in
diabetics. There was no toxic side effects identified using such a high dosage of
vanadium.130
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Boron

Boron is distributed throughout the human body with the highest concentration in bone. Boron seems to be essential for healthy bone and joint function. It affects cell membranes and the way signals are transmitted across these membranes and has a significant role in nerve signal transmission. It also plays a role in converting vitamin D to its more active form, thus increasing calcium uptake. A boron deficiency may also decrease mental alertness.131
Toxicity: There is no RDA for boron. A safe and adequate daily intake is estimated to be
between 1 and 10 mg. Toxic effects appear at intakes of about 100 mg. A fatal dose in
adults is 15 to 20 g and in children 3 to 6 g.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.

Page 24 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
Germanium
GE-132 Sesquioxide is the organic form of germanium. It is the active ingredient in garlic and is found in other botanicals including aloe vera and comfrey. In the 1985 Sept/Oct edition of Anticancer Research a study which showed positive results with animals inoculated with cancer cells and then treated with germanium showed an increase in the body's defense mechanisms.
GE132 was to be identified as an oxygen catalyst, body detoxifier, an adaptogen, and
most importantly an electrical impulse stimulator.
GE-132 may stimulate production of gamma-interferon providing relief to CFS
patients.132
In clinical research with patients suffering with chronic fatigue syndrome, clinicians report
that between 20% and over 50% of their patients given GE-132 150-500mg./day showed
substantial symptom relief .133
Toxicity: GE-132 was evaluated by the Welfare Ministry of Japan and is listed in their
"Guidelines for Manufacturers". Animal and human studies confirmed that GE-132 is
safe in humans up to the equivalent of ten of grams per day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Methionine

Methionine is one of the sulphur containing amino acids and is important in body function. It acts as a lipotrophic factor in preventing excess fat buildup in the liver and the body.
Toxicity:
There is no toxicity rating for methione.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Phenylalanine

Phenylalanine is very important to CNS function as it a precursor to the amino acid tyrosine. The neurotransmitters norepinephrine and dopamine are precursored by tyrosine. Without tyrosine the production of these very important transmitters would cease.
In an observational study involving 28 patients with ADHD the plasma phenylalanine
levels were determined and compared to 20 controls. The ADHD group has significantly
lower plasma levels of phenylalanine, suggesting that deficiency may be one of the
underlying causes of ADHD.134
Toxicity: There is no toxicity rating for phenylalanine.
Page 25 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Bioflavenoids

The bioflavenoids have a vitamin C like effect providing general health to the body and cellular mass. "Proanthocyanidin" is one of the names used to describe a powerful bioflavonoid complex known as Procyanidolic Oligomers. Proanthocyanidin is one of the few antioxidants that crosses the blood/brain barrier to protect neural cells.
Flavonoids were discovered by Nobel Prize-winning biochemist Albert Szent-Gyorgi,
who labeled them "Vitamin P". He discovered that they enhanced the function of vitamin
C, improving absorption and protecting it from oxidation. Citrus bioflavonoids have been
well researched and studied in human nutrition.
Toxicity: There is no stated toxicity for bioflavonoids.

EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.


Grape seed extract

Grape seed extract, like bioflavonoids have a Vitamin C – Vitamin E like effect providing general health to the body and cellular mass. Proanthocyanidins have been used therapeutically for decades in Europe to improve circulation, reduce edema and varicose veins.
Toxicity: There is no stated toxicity for grape seed extract.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.

Inositol
Inositol is a B vitamin which is closely associated with choline. It's concentration in the human body is the second highest in the B vitamins. Inositol expressed as phosphatidylinositol has function in cell structure and when combined with choline it provides a source of brain cell nutrition. In a double blind controlled trial, 12 grams/day of inositol, were administered to 28
depressed patients for a four-week period. A significant benefit for inositol compared to
placebo was found at week 4 on the Hamilton Depression Scale. Frequency and severity
of panic attacks and severity of agoraphobia declined significantly with inositol compared
to placebo. Side effects were minimal. The same researchers also tested the
effectiveness of inositol supplements in panic disorders and obsessive compulsive
disorder, and found beneficial effects. 135
Inositol supplementation treats agoraphobia and panic attacks. In a double blind crossover trial 21 patients suffering with panic attacks with or without agoraphobia were Page 26 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001
administered 12 grams of inositol and placebo in random order for 4 weeks each. The
frequency and severity of the panic attacks and agoraphobia were significantly less
when using inositol vs. the placebo.136
Inositol is a component of cell membranes and the myelin which insulates nerve fibers.
Toxicity: No deficiency or toxicity has been identified for inositol, in spite of its presence
in a wide variety of foods.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Gingko Biloba

Gingko is a herb which has been proven to have the effect of vascular dilation. Hence it has been proven to have a positive affect in Dementia and ADHD providing increased blood flow to the brain and central nervous system. Ear problems are improved with Gingko Biloba, due to improved blood flow to the nerves to the inner ear. It has been found to assist patients suffering with chronic ringing in the ears (tinnitus).
Toxicity: There is no stated toxicity for gingko biloba.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Glutamine

Glutamic acid, the precursor to the amino acid gluamine is found abundantly in vegetable proteins. Glutamine is concentrated in the brain and with the combining of Vitamin B6 forms (gaba) gamma-aminobutyric acid, an important neurotransmitter. Thus glutamic acid has been associated with successful treatment of schizophrenia, and other brain disorders.
Toxicity:
Not established - glutamic acid is very common in human food products.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.
Choline (B vitamin)

Recent evidence suggests that choline is an essential nutrient in humans. Small quantities are synthesized in the liver with the help of Vitamin B12, folic acid and the amino acid, methionine. Choline is an important component of cell membranes and assists in the transmission of signals inside cells. Myelin contains choline and is the insulating fabric around the nerves. Choline precursors the synthesis and release of the neurotransmitter acetylcholine, which is involved in nerve and brain function. Choline deficiency in animals has been proven to cause nerve degeneration and dementia. Page 27 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 Choline has been used to treat brain disorders such as Alzheimer's disease and Huntington's chorea, in which acetylcholine levels are low. Some studies have shown improvements in mental performance after choline
treatment.137
In a 1994 study, lecithin was given to patients with Alzheimer's disease daily in doses of
1000 mg for 30 days. Results showed slightly improved mental performance.138
Choline supplements have been shown to provide benefit in the treatment of bipolar
disorder.139
Five out of six patients with Bipolar disorder showed significant relief of symptoms
following the administration of a choline supplement.140
Bipolar patients (10) treated with choline achieved a permanent remission of mania.141
A clinical trial with 70 ADHD children and adolescents using choline provided positive results. All trial patients demonstrated some positive results. Titration occurred to 3000 mg/day of choline.142
Toxicity:
The tolerable upper intake limit has been set at 3g/day.
EMPowerplus at the full loading dose of 15 capsules or 4 scoops of powder per
day contains minimal amounts of this nutrient.

2.5 Combined Nutrient Supplementation Research
A double blind study, with 62 jailed delinquents ages 13-17 took a vitamin-mineral
supplement for 3 months. A significant difference was found between the active group
and placebo group for violent and non-violent antisocial behavior following the trial. The
study showed 113 violent acts during the baseline and 11 during intervention.143

Another controlled study investigated 40 children housed in a correction facility using a
vitamin-mineral supplement for a 6-week period. Rule violations for the previous 6 –12
weeks were compared to the number of rule violations while the children were
supplemented showing a significant change in behavior. Fifty-five percent or 22 subjects
stopped getting into trouble altogether.144
A nutritional supplementation study researched a high potency broad spectrum product.
Twenty-three agoraphobic patients used the nutrient for 3 months. Nineteen of the 23
patients showed significant improvement (dramatic) and 11 of the 19 were free of panic
attacks.145
3. Possible Interfering Factors

The human body is a marvelous organism with all faculties and facilities necessary to
control and regulate itself. It is homeostatic, always seeking to bring itself to a state of
balance. An example of this is the blood sugar control system operative within the body.
Page 28 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 If we increase the intake of sugars, our body will move immediately to reduce and control plasma sugar levels by introducing insulin as a control mechanism, thereby bringing plasma sugar levels within a defined set of parameters. Another example is the CNS's ability to regulate the levels of various neurotransmitters. If the correct level of nutrients is found within the body it can accomplish the task and adapt to its ever-changing internal and external conditions. Unfortunately there are factors which interfere with this homeostatic system, causing the body to lose control. Here we will briefly discuss some of those factors, which by experience we have learned have negative effects on CNS balance. a. Street Drugs can cause a major imbalance in CNS function. Street Drugs cause
an in-balance in CNS function by altering the bio-chemical state of the individual. When street drugs are used in combination with the Truehope program the participant will ultimately regress due to an inability to maintain adequate neuro-chemical balance. This includes the use of botanicals such as marijuana and hashish as well chemicals such as PCP, DMT etc. b. Medications whether prescribed or un-prescribed may adversely affect the
operation of the CNS. For example, the use of anti-psychotics and
antidepressants in combination with the program will manipulate the CNS out of
balance. One cannot restore the proper neuro-chemical balance and remain on a
medication e designed to alter that balance. For example, Ritalin may stimulate
the ADHD patient positively, but Ritalin given to an individual not suffering with
ADHD will cause that individual to experience an abnormal mood elevation. All
Medications should be closely looked at to determine their affects on CNS
operation. Even if a medication does not directly influence CNS function it may
have a negative affect as a secondary factor. For example medications that
affect the digestive tract can also effect CNS operation. Tagamet, Prilosec and
other anti-acids reduce the level of hydro-chloric acid in the stomach. This
reduction interferes with the body's digestion of food (especially proteins) and
throws the body into a nutrient deficient state. Any over the counter medication
containing a psycho-active ingredient, such as codeine, will interfere with the
body's response to the Truehope program.
Quote:
"Even its basic makeup defies logic. Salt is a blend of sodium and chlorine – the
first is a metal so unstable that it bursts into flame when exposed to water; the
second a lethal gas. When we swallow the blend, it forms hydrochloric acid in our
stomachs…Suicidal? No, an absolute necessity for life."- G Young, National
Geographic
c. Antibiotics taken orally have a negative effect on the Truehope program. When
an antibiotic is introduced into the stomach it will unselectively destroy more of the micro-flora than just a single pathogen. Normal levels of micro-flora in the digestive tract are absolutely essential for the breakdown of food and release of nutrients to the body. Compromised levels of micro-flora therefore create element deficiencies. Anti-biotics will always exacerbate symptoms of a CNS disorder and may completely negate the benefits of the Truehope program. If antibiotic use is required we have found that taking it intravenously or intramuscularly will prevent its damaging effect on intestinal micro-flora. Supplementation with live bacterial Page 29 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 cultures may help to restore compromised levels of intestinal bacteria as well. d. Caffeine acts as a CNS stimulant destroying CNS balance. The following
research bears this out: Beck Depression inventories were higher with a group of healthy college
students who were moderate to high caffeine consumers, academic scores were
also lower. Low caffeine consumers scored better (lower) on the depression
scale.146

In another study with depressive patients who were consuming >750 mg. daily of
caffeine, 50% showed severe depression as rated on the Beck Depression
Scale. Such scores were significantly higher than low or moderate users of
caffeine in the same population.147
A double blind case trial indicated that a patient with emotional stress was
improved using a sugar – caffeine free diet. The patient was tested with sugar
and caffeine under double blind conditions. Only a use of caffeine brought a
return of the depressed mood.148
Caffeine has been shown to increase serum concentrations of adrenaline and
nor-adrenaline, having the effect of increased depression and anxiety.149 150
The New England Journal of Medicine reported on the following double blind
study: 62 normal adults with low to moderate caffeine intake were studied at
baseline, they randomly received caffeine or placebo capsules. The subjects had
abnormally high scores on an Anxiety measure (State-Trait Inventory Score)
during withdrawal (placebo period). Thus demonstrating the addictive nature of
caffeine and the resulting anxiety associated with withdrawal.151
e. Herbals in some instances can offer significant answers to particular problems
just being "natural" however does not make them either efficacious or safe. For example, a young female participant suffering with bipolar disorder (principally depression) was finding significant resolve to her disorder taking the Truehope program. Her menstrual cycle brought back some symptoms of depression, which her mother decided to address temporarily with St John's Wort. The next morning her parents were awakened to find their 17-year-old daughter kneeling and praying in the middle of the city street with cars driving around her. St Johns exerts has a drug like effect on the body similar to number of prescription anti-depressants. This ability when combined with the chemical restorative properties of EMPowerplus creates an ADR (Adverse Drug Reaction) which is also similar to the prescriptive drug medications. The over production of serotonin created in either case has the potential to elevate mood to a state of severe mania and delusion. Any herbal preparation that has a psychotropic effect should not be used in conjunction with the Truehope program. Such preparations include MaHuang, Guarana, Ephedera and its extracts, to mention only a few. It is important to be fully aware of what you are taking and their potential effects. Page 30 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 f. Alcohol interferes with CNS operation in a powerful way. Much research has
been completed on the effects of alcohol and its use in relation to CNS disorders.
"Intoxication with brain depressants, especially alcohol, can cause clinically
relevant changes in mood, with prolonged intoxication likely to induce depressive
symptoms that resemble those seen in major depressive disorder".152
"Depression and drug abuse may be associated with alterations in some of the
same neurotransmitters systems".153
Depression may be engendered with the use of alcohol by reducing CNS
catecholamine levels.154
Alcohol use may increase brain serotonin levels, and may have a reversal effect
as its effects wear off, creating a vicious cycle of self medicating.155

Of all of the systems in the human body none is more sensitive then the Central
Nervous System.
g. Tobacco has a negative effect on body health and longevity. Its use will only
promote general illness. Nicotine exerts a powerful psychotropic effect on the nervous system.
h. Yeast in many situations is created by antibiotic abuse. The intestinal micro-flora
is altered with antibiotic use, giving candida an opportunity to flourish. Candida robs the body of nutrients in a parasitic fashion creating a state of deficiency throughout the body. There are many products available to assist with yeast control. i. Parasites also rob the body of nutrients and like yeast can create deficiencies.
j. Flu and other transient illnesses create instability in program participants. One
cannot benefit from nutrients that cannot be kept in the system. Vomiting or diarrhea prevent the body from obtaining any benefit from the supplement. Constipation also interferes with intestinal function and therefore the uptake of nutrients becomes compromised.
k. Immunizations can have the same interfering effect as an illness. As the body
uses its resources to defend itself from foreign invasions by pathogens, the body's nutrient resources become depleted and are less available for normal CNS function.
l. HRT (hormone replacement therapy) or the replacement of any natural
hormone has the potential to create an imbalance in the regulation of body function. This would include the use of thyroxin. The use of any of these hormones would require careful monitoring by competent measures to ensure that correct balance is maintained. The use of EMPowerplus has the potential to restore proper hormone balance thus the requirement to monitor hormone levels. m. Fad diets can create problems for the participant. Limiting varieties of food types
on crash diet plans can affect body chemistry. Drinking excessive amounts of Page 31 of 38 Truehope Nutritional Support Ltd., Copyright January, 2001 water can flush needed body minerals out of the kidney, also creating deficiencies. Even limiting salt intake to excess can be harmful.
Summary: This list is not all-inclusive. There are many more concerns, which could
be addressed including: sleep deprivation, over-consumption of refined foods and
sugars, disease of the bowel, persistent loose and / or watery stool, constipation,
irritable bowel syndrome, over-use of laxitives, irregular sleep and meals, and over-
use of antacid medications.

4. Conclusion

In preliminary studies, EMPowerplus has shown to be a safe and effective way of
treating the symptoms of Bipolar Disorder and other types of mental illnesses. We are
confident that further research will ultimately prove that many types of mental disorders
can be effectively treated using carefully formulated vitamin and mineral
supplementation.
Questions about this manual or about the EMPowerplus program of supplementation
and support can be directed to Truehope Nutritional Support Ltd. at 1-888-878-3467.
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ARTICLE 48. CONTROLLED SUBSTANCES IC 35-48-1 Chapter 1. Definitions IC 35-48-1-0.1Application of certain amendments to chapter Sec. 0.1. The addition of section 9.3 of this chapter by P.L.225-2003 applies only to a controlled substance offense underIC 35-48-4 that occurs after June 30, 2003.As added by P.L.220-2011, SEC.627. Amended by P.L.63-2012,SEC.81.

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Oncotarget, Advance Publications 2015 Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphomaJiao Ma1, Wei Xing2, Greg Coffey3, Karen Dresser2, Kellie Lu4, Ailin Guo5, Gordana Raca6, Anjali Pandey3, Pamela Conley3, Hongbo Yu2, Y. Lynn Wang51Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY2Department of Pathology, University of Massachusetts Memorial Medical Center and Medical School, Worcester, MA3Department of Biology, Portola Pharmaceuticals, Inc., South San Francisco, CA4University of Chicago Laboratory School, Chicago, IL5Department of Pathology, Division of Genomic and Molecular Pathology, University of Chicago, Chicago, IL6Department of Medicine, University of Chicago, ILCorrespondence to: Y. Lynn Wang, e-mail: [email protected]: diffuse large B cell lymphoma, cerdulatinib, SYK, JAK-STAT, molecularly targeted therapyReceived: May 27, 2015 Accepted: