This article is about dementia but in it Dr. Hyman discussed how genes are like a gun and environment pulls the trigger. This article is where I got the words I used. I'd like to see you call him silly. I'm sure you mean nothing by it but the latest research says that the genes only determine how each person's body will handle the toxins. Without the toxins or mal nourished cells there would be no degenerative disease. Think about it. In the wild far away from man and his pollution animals do not get heart disease, diabetes, cancer etc... Put them near man or actually fed by man and all of a sudden they get our illnesses. Go figure that one out, silly. (just kidding)
Read this article though, it is very interesting. I'll cut some of it out but go to the link and read the whole thing it is great.
http://www.ultrawellnesscenter.com/downloads/Dementia-Myth.pdf10 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Does Dementia Exist?
Mark A. Hyman, MD, is the editor in chief of Alternative
Therapies in Health and Medicine. (Altern Ther Health Med.
2008;14(2):10-12.)
The great enemy of truth is very often not the lie—deliberate, contrived
and dishonest—but the myth—persistent, persuasive, and unrealistic.
Too often we hold fast to the clichés of our forebears. We subject all
facts to a prefabricated set of interpretations. We enjoy the comfort of
opinion without the discomfort of thought.
—John F. Kennedy
Obesity is obvious. Just look around the American
landscape. But memory loss and cognitive decline is
invisible—and more fearsome. Alzheimer’s disease
will affect 30% (and some experts say 50%) of people
over 85 years old, which is the fastest growing seg-
ment of the population. The prevalence of Alzheimer’s is expected
to increase 3-fold by 2050 affecting 14 million people, at an annual
cost at $83.9 billion to our healthcare system and society,1 which
doesn’t even begin to account for the untold suffering on families
and caregivers. It is now the seventh leading cause of death.2
With Alzheimer’s we are facing a global problem. It is project-
ed to increase 285% in North America, 534% in South America,
476% in Africa, and 497% in Asia by 2050.3 Even small progress in
preventing the disease and slowing its progression will have a pro-
found impact on the personal and fi nancial costs we will bear.
If we want to do something other than provide palliative care,
we must ask certain questions. What is dementia? What causes it?
Is it uniformly the same disease or the heterogeneous manifestation
of multiple genetic and environmental insults? Can it be prevented?
Can it be slowed, stopped, or even cured? And why are we seeing
growths of epidemic proportions of the incidence of cognitive dys-
function, mild cognitive impairment (MCI), and dementia?
Conventionally dementia falls into 2 main categories—Alzheim-
er’s and vascular dementia, with many other minor variations.
Therapy is limited to 2 main categories of medication—acteylcholin-
esterase inhibitors and NMDA (N-methyl D-aspartate) receptor
antagonists, neither of which addresses the causes of dementia and
both of which are marginally effective (if at all) and have signifi cant
side effects. New treatments such as vaccines are on the horizon.
Emerging research indicates that inflammation, oxidative
stress, insulin resistance, and mitochondrial dysfunction are key
mediators of brain degeneration. But rarely is the question explored
as to why these processes occur. What are the proximal causes? Is
there another clinical model for preventing, treating, and even
reversing cognitive decline and dementia? Even more, mounting
research suggests that loss of cognitive function is not a homoge-
neous process and that Alzheimer’s or dementia is not a single dis-
order but a common clinical manifestation of disordered neuronal
function arising from a multitude of genetic, environmental, and
lifestyle factors unique to each individual. Even if large-scale system-
based clinical trials are yet to be done—or diffi cult to do—if we can
assemble existing data into safe lifestyle-based and nutritional inter-
ventions for optimizing brain function, then we might hold back
the tsunami of broken brains and broken lives we face.
HEALING THE MIND AND REVERSING DEMENTIA: IS IT
POSSIBLE?
New research suggests that focusing on the “disease” called
dementia and fi nding drugs to modify downstream effects of brain
injury such as insuffi ciency of acetylcholine misses the opportunity
to address the real problems. In fact, “dementia” does not exist but
is simply a common collection of symptoms that explain nothing
about the underlying etiology or pathophysiology. These include
infl ammation, oxidative stress, insulin resistance and other hor-
monal dysregulation, mitochondrial dysfunction, nutritional defi -
ciency, and toxic injury. The question is not how to treat dementia,
because it is not a single disorder, but how to fi nd the underlying
reasons for our broken brains and how to fi x them.
The cognitive dysfunction we call dementia is simply the way
the body expresses injury to a myriad of insults that can be quite
different from person to person. No 2 “dementias” are exactly
alike. But how do we apply molecular personalized genomic medi-
cine to such a complex disorder?
The answer is quite simple. Ample science lays out the pat-
terns of dysfunction in dementia and, to a great degree, most of the
precipitating causes. Then our individual genetic differences and
predispositions set us up for biological breakdown from the same
few common insults—toxins such as mercury, digestive imbalanc-
es, nutritional defi ciencies or excesses, stress, allergens, infections.
These in turn, lead to the altered physiological processes we see in
the “dementias”—infl ammation, oxidative stress, mitochondrial
dysfunction, and insulin resistance.
We have to think about individuals, not diseases. In medicine
our differences (genetic predispositions, environmental exposures,
diets, and stresses) are more important than our similarities.
Sometimes the practice of medicine lags behind the science, and
sometimes the practice gets ahead of the science. Genetic testing
DOES DEMENTIA EXIST? DISPELLING THE MYTH
Mark A. Hyman, MD
Editorial
ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 11Does Dementia Exist?
puts us squarely in the middle of that dilemma.
We are at a crossroads where the old ideas we have about dis-
ease and diagnosis become less meaningful as we understand more
and more about the importance of individual differences in deter-
mining illness. This is a time when personalized medicine will
replace medicine based on diagnosis and disease. In fact, disease
and diagnosis as we know it (ICD-9 classifi cation of diseases) will
soon be an obsolete concept, an artifact of medical history like
bloodletting or phrenology (the art of diagnosis based on the shape
of your skull, popular in the 19th century).
AN “N” OF 1: REVERSING DEMENTIA
As a medical student, I participated in a public health research
project in a remote Nepalese village. In exchange for the villagers’ help,
we offered an improvised outdoor medical clinic. One man brought
his mother to our clinic after carrying her on his back for 10 days
through the Himalayas. I asked how we could help. He said his mother
was blind. She had cataracts. There was nothing we could do.
That is how I felt about my patients with dementia until I met
“George.” George presented with dementia. His story is an exam-
ple of how treating a person—not a disease—leads to improved
clinical outcomes; how environmental infl uences on genetic predis-
positions—mostly mercury exposure in this case—can lead to any
number of diseases depending on individual genetic variations.
George presented with a diagnosis of dementia after a com-
prehensive neurological evaluation including neuropsychological
testing, MRI (magnetic resonance imaging), MRA (magnetic reso-
nance angiography), and SPECT (single-photon emission comput-
erized tomography) scanning. When he came with his wife to see
me, he could no longer manage his business affairs, had become
increasingly unable to function at home, and had to withdraw from
family and social relationships.
HOW THE ENVIRONMENT AFFECTS YOUR GENES: A CASE
OF MERCURY POISONING
Chronic diseases, like Alzheimer’s, cardiovascular disease, or
cancer are usually multi-gene disorders. It is not 1 gene but the
interaction between many genes, their variations or single nucle-
otide polymorphisms (SNPs), and the environment that puts
someone at risk for a chronic disease such as dementia. That is why
we will never fi nd “the” gene for Alzheimer’s—or heart disease,
cancer, autism, or depression.
In the case of George, whose mind and life were evaporating, I
looked deeply into his genes and the biochemistry his genes con-
trolled and found places we could improve things. He was homozy-
gous for apo E4, a high-risk gene for Alzheimer’s disease4 that also
predisposes to dyslipidemia and impaired heavy metal detoxifi ca-
tion from the brain.5
A 6-hour DMPS provocation challenge test for heavy metals*
revealed mercury of 350 mg/g creatinine (normal < 3 mg/g creati-
nine). Sources of mercury include vaporization of dental fi llings or
environmental exposures from tuna fi sh or air pollution.6 George
lived his life in an industrial area with large coal burning plants and
had many dental amalgams.7 Mercury toxicity is a potent neuro-
toxin linked to many neurological disorders including dementia.8
In one study of 465 patients with chronic mercury toxicity,
32% had severe fatigue, 88% had memory loss, and almost 30% had
depression. These symptoms and mercury poisoning were much
more common in people with the apo E4 gene. Removal of amal-
gam fillings combined with a mercury detoxification program
resulted in signifi cant symptom reduction.9
Other genes act synergistically with apo E4 to amplify risk.
Common polymorphisms of genes regulating glutathione metabo-
lism, the main detoxifi er of metals in the body, such as glutathione-
S-transferase (GST),10 increase risk of cognitive impairment.
Combinations of GST and apo E4 polymorphisms further increase
risk for dementia.11 George carried the GSTM1 null or absent SNP.
Carriers of the null (or absent) polymorphisms for GST have higher
total body burdens of mercury.12 Genes load the gun, and the envi-
ronment pulls the trigger.
George had an elevated homocysteine and was homozygous
for methylene tetrahydrofolate reductase (MTHFR),13 which
impairs methylation and increases homocysteine, which can dou-
ble the risk of dementia.14 Disruptions of 2 key interdependent,
interconnected biochemical cycles are at the root of the physiologi-
cal dysfunction we see in most chronic diseases. These are the
methylation and trans-sulfuration (glutathione metabolism) cycles.
They are necessary for proper detoxifi cation and redox balance, as
well as modulation of immune response, control of gene expres-
sion, membrane function, and more. Polymorphisms in any of the
enzymes facilitating these cycles may increase the risk of chronic
disease, particularly neurologic and psychiatric disorders such as
dementia, autism, ADHD, and depression. Adequate concentra-
tions and active forms of nutrient cofactors involved in these cycles,
especially methylcobalamin (B12), 5-methyl-tetrahydrofolate
(5-MTHF), and pyridoxine (B6), as well as adequate dietary sources
of sulfur are essential for proper function of the methylation and
sulfation cycles.
Lastly, George had a polymorphism of cholesterol ester trans-
fer protein (CETP). This gene limits HDL reverse transport of cho-
lesterol and increases risk of hyperlipidemia. CETP polymorphisms
act synergistically with apo E4 to increase the risk of dementia.15
For George, those SNPs (apo E4, GSTM1, MTHFR, CETP)
acted synergistically to increase his risk and made him in one way
or another susceptible to environmental insults from mercury
overload, nutritional defi ciencies of folate or B
12, and dietary infl u-
ences on cholesterol and insulin sensitivity. Other studies show
similar polymorphisms in autism16 and depression.17 In fact, these
may be simply different manifestations across the age spectrum of
the same “disease.” The genetics, biochemistry, and physiology of
these conditions overlap and arise from common roots. What is
critical to remember is that these genes are highly regulated and
their expression modifi ed by nutrient and lifestyle inputs.
*Blood levels of mercury only refl ect recent exposure from pollution or fi sh consump-
tion, but a provocation test identifi es total body burden of mercury. Studies have
found that using DMPS increases mercury excretion from 3- to 107-fold. The chelating
agents or drugs, DMPS and DMSA, are both used to treat heavy metal toxicity.
PERSONALIZED MEDICINE: A CURRENT REALITY OR
FUTURE POSSIBILITY?
Based on George’s unique genotype and his phenotypic
expression (elevated body burden of mercury, hyperlipidemia,
insulin resistance, hyperhomocysteinemia, low glutathione, and
impaired detoxification), a therapeutic plan was developed to
address his entire systemic dysfunction. George also had a 30-year
history of irritable and infl ammatory bowel diseases, which has
been linked to dementia and other neuropathologies.18
The single gene, single disease, single drug model is inappro-
priate for complex multi-gene systemic disorders with common
manifestations but differing etiologies such as dementia. The com-
ponents of his therapeutic plan were design to remove toxic trig-
gers (mercury, poor diet, dysbiosis), while optimizing
nutrient-regulated gene expression. Doing just one thing wouldn’t
help George. Treatment required addressing all the imbalances,
the causative factors, and their effects systematically.
Treatment included careful mercury detoxifi cation including
safe amalgam removal and chelation.19 Phytonutrients and nutrients
that upregulate glutathione, including cruciferous vegetables such as
kale, watercress, and cilantro; herbs such as milk thistle; nutrients
such as selenium and zinc, were added to his diet. His hyperlipi-
demia and insulin resistance were managed with a low glycemic
load, plant-based high-fi ber whole foods, organic diet, and exercise.
To further improve his genetic limitations in methylation and
sulfation, he was treated with high doses of MTHF (methyl-tetra-
hydrofolate),20 methylcobalamin,21 and B
6. To address his gut
infl ammation, food allergens were eliminated, small bowel bacteri-
al overgrowth was treated, and enzymes and probiotics were
replaced. Additional basic nutritional support, including a multivi-
tamin and omega 3 fatty acids,22 was provided.
After a year of aggressive therapy that was matched to his
quirky genes and biochemistry—not his diagnosis—George had a
remarkable and dramatic recovery. Before I saw him, he could not
manage his business nor did his grandchildren want to be around
him. After matching his treatment to his genes, he was again to
function able, and his grandchildren loved being with him.
Although this area of genetic testing and nutrigenomics is
new and more research is needed to help us refi ne our understand-
ing and treatment, there are ways to look through new doors into
an entirely new era of medicine—one that no longer focuses on the
disease but on the person and his or her uniqueness. Widespread
gene testing is not ready for primetime, but it can be a helpful
guide in understanding the origins and the risks of some chronic
illnesses. But we have to recognize that it is the interplay of many
genes interacting with the environment that determines our
health. What we do know is that there is no single gene for
Alzheimer’s—or autism, depression, heart disease, or cancer. In
fact, those diseases, as single homogeneous, uniform conditions,
do not exist. We must give up that myth.
Instead, there are common variations in the symphony of our
gene patterns that are integral to many chronic diseases. These
patterns vary from person to person and are highly infl uenced by
diet, stress, infections, allergens, and toxins.
The time has come to focus on systems approaches to com-
plex systems disorders. Treatment based on mechanism, genetics,
biochemistry, and physiology will supplant diagnosis-based treat-
ment. Clinicians can begin to navigate with a different map for the
territory of illness than the one we received in our training and in
the process can become re-enchanted with medicine and the possi-
bility of healing where there was none.
REFERENCES