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The Biophysics and Biochemistry of Fatigue and Obesity:
Energy and Information, the fabric of reality and our health
Hugo Rodier, M.D.
In
every physician’s practice, two problems in different degrees of
severity are seen in the vast majority of patients: fatigue and
obesity. That they are related is not only a common sense
observation, but that they are involved in practically all
diseases we encounter as physicians may not be as apparent. This
article attempts to bring together recent advances in many
diverse fields of endeavor in medicine, psycho-neuro-immune-endocrine
systems, nutrition, environmental health, biophysics and
biochemistry from a generalist’s perspective, perhaps too broad
and not detailed enough for some. Yet, the need to integrate new
understandings of cellular concepts (“we have been barbarians
at the gates of cellular function,” (J. Biol Chemistry
1998;273:1269) is pressing.
A failure to communicate
Insulin resistance (IR) is the simple mechanism behind
our country’s epidemic of obesity and diabetes. IR suggests that
there is a partial resistance to insulin at the cell membrane
level of all 100 trillion cells making up our bodies. This is
happening because the outer skin of every cell in our body,
whether they are brain cells, heart cells, or the cells in a
hangnail, are TOILing: our cell membranes are:
T-toxic,
O-oxidized,
I- Inflamed, and
L-Light, or energy/love deprived;
Less mitochondrial function.)
(“Neuroprotection
in Parkinson’s Disease,” JAMA 2004;291:358.)
Cell membranes are delicate structures that must be flexible and
soft, which is naturally the case, when we eat the right
proteins, sugars, and fats (J. Nature, December 14th,
2006.) Since we are eating mostly refined/transhydrogenated
fats, refined sugars and proteins highly processed with
steroids, antibiotics, hormones and pesticides, our cell
membranes are growing stiffer, thus, less responsive to the “messages
of cell communication.” Environmental pollution contributes
to this process, as emotional/spiritual issues do.
Hormones, like insulin, neurotransmitters, enzymes,
etc., may be thought of as molecules or messengers that cells
produce to communicate with one another (J. Science November 26th
2004: October 7th, 2005.) The whole network of cell
communication should not have been divided into different
systems. Now, it is widely accepted that this system called the
“Psycho-Neuro-Immune-Endocrine system” works as an
undivided network of communication (“Pain and stress in a
systems perspective: reciprocal neural, endocrine and immune
interactions,” J. of Pain 2008:9;122.)
Understanding that this network is a unified way to relay Energy
and Information (E&I) to every cell of our body brings about a
holistic perspective to health and disease: each messenger of
E&I may function in any of the components of this system. For
instance, one of the most powerful neurotransmitters, or
messengers that relay information back and forth in neurological
tissues, like serotonin, or dopamine, is the thyroid hormone (J.
Frontiers in Neuroendocrinology 2001;221.) And insulin is also a
neurotransmitter (“Insulin effects weigh heavily on
the brain,” JAMA 2006;296:1717) and in its most simplified
role, it is the quintessential messenger of E&I.
Our cells and E&I
Each cell membrane of our 100 trillion cells has “receptors”
to which these messengers attach in a “lock-and-key”
fashion. If the cell membrane is healthy, messages of E&I enter
the cell to be interpreted in the nucleus of the cell. No matter
what kind of cell we are interested in, it cannot do its job
without E&I.
If you are particularly fond of spiritual issues, you may use
the words “Light,” and “Love,” instead of E&I.
Many feel that Light, Energy, and Information are two sides of
the same coin. After all, communication of information is
achieved through energy, or light waves.
Cells communicate E&I to each other for our body to function as
one single entity, or one consciousness. This is the message we
get from ages and pages from the dustbin of history books and
from thrilling modern research, particularly in physics. Cells
communicate in order to process and consume E&I, which is the
modus operandi of the whole Universe (“Programming the
Universe,” Seth Lloyd, 2006, Alfred A. Knopf press.) If your
religious beliefs are foremost in your mind, please, equate “energy/light”
with God, and “information/communication” with His
Gospel.
The E&I that comprise the whole Universe are funneled to humans,
and the whole Earth for that matter, through the light of the
Sun (“The Electric Universe,” Thornhill and Talbot.) E&I
from the Sun are stored in the food we eat. Simply put, food is
the most practical way of getting E&I. Our SAD diet, the
Standard American Diet is providing such poor and toxic food
that TOIL is seen.
Through photosynthesis in plants and vitamin D in our skin we
harness solar E&I, which fuel all function and the structuring
of our body, particularly our heart. Many feel that it is not a
metaphor that our hearts are the center of knowing, feeling, and
our very consciousness, not the brain. In fact, our hearts have
5,000 times more electromagnetism than the brain (“The Heart
Code,” Dr. Paul Pearsall. Broadway Books, 1998.)
Insulin resistance = “sweet death.”
Once we focus on E&I, the pillars of Reality, we can see that
these simple principles not only rule the stars, the planets,
and atoms, but everything else in between, including living
organisms. For humans, the most important messenger E&I in our
bodies is the hormone insulin, since it brings E&I, or
glucose (energy) to all cells for them to carry out whatever
function they specialize in. The main problems in our society,
obesity and diabetes are simply IR issues, or
dysfunctional cell communication of E&I. Cool Hand Luke would
agree: “what we got here… is a failure… to communicate.”
TOILing of cell membranes is the root of IR. If cell membranes
are TOILing and causing IR, it is not far fetched to assume that
all other messengers of cell communication found in the PNIE
system of cell communication are also meeting with resistance.
Would this process not lead to fatigue? The National
Institute of Health has recommended that Chronic Fatigue
Syndrome be renamed the Psycho-neuro-immune-endocrine
dysfunction syndrome (J. Functional Medicine Update, 2003;2339.)
Understandably, this tongue-twister of a name did not catch on.
Think about it: if cell membranes develop resistance to only
insulin, they are discriminating against insulin. Why would they
block insulin and yet easily allow other messages of cell
communication to freely enter the cell? If we have IR, we also
have resistance to practically all other messages, because our
cell membranes are TOILing; we may also have thyroid resistance,
adrenal hormones resistance, neurotransmitter resistance, etc.
Taking out the garbage
If
we eat good food we fix the cell membrane TOILing, so that E&I
from the food we eat may enter the cell to fuel whatever
function that cell is responsible for. A good diet will also
optimize the pathways of detoxification in charge of eliminating
not only the toxins that we produce ourselves in the process of
metabolizing E&I, but the toxins we encounter in our processed
food and polluted air, water and soil. If they are not properly
eliminated, the cell membrane TOILs: The “T” is for toxicity,
but “O” for oxidation, “I” for inflammation and “L” for lack of
optimal mitochondrial function are also worsened by these
toxins. The components of TOIL are interrelated and
exchangeable.
But, to complain about environmental pollution, without the
understanding that we need E&I to function as a society is, in
my opinion, a bit naïve. Some of us, meaning well, and having
worthy goals, complain about environmental pollution and try to
shut down energy industries, while they jet around, drive
expensive cars, live in huge mansions in the hills and use every
imaginable gadget, all of which consume enormous amounts of
energy to communicate their outstanding resolve to clean up
planet Earth. Instead, we would do better to focus on an
integrative view of E&I, so that we transition from polluting
technologies to cleaner and more sustainable sources of E&I with
the least amount of disruption to our society. It will not be
easy and surely harder if we keep fighting with the zeal of
righteousness ringing in our outraged speech.
Our
bodies are also struggling with free radicals, or toxins. Each
cell, after using up the E&I we ingest in the form of food,
needs to get rid of “metabolites,” or the garbage
produced by the “energy-processing” structures within the
cell, specifically the mitochondria. These metabolites are also
known as “free radicals,” “oxygen reactive species,”
and “oxidants.” Just as we have specialized cells to
bring in E&I into every cell (G.I. tract, lungs, heart, and
circulatory system,) we have cells that have specialized in
getting rid of the garbage produced by all our cells. The “garbage
processing” cells make up the organs that take out the
garbage: our intestines, liver, skin, and kidneys.
E&I, and food
Our bodies need a constant intake of E&I, or food, in order to
maintain the cycle of “creation-destruction” in our body,
a cycle underlying all of nature. Think of food as a practical
source of E&I. Just like any engine, we must obey the basic
Universal principles of thermodynamics (I do not think we are
machines.) We need fuel and an efficient way to get rid of the
products of combustion. Imagine pumping bad fuel in your car’s
engine while a pair of socks is stuck in the exhaust pipe. It
wouldn’t get very good gas mileage, would it?
Eating poorly, and having poor “energy” from
emotional/spiritual/mental relationships provides poor fuel for
our cells or sub-par levels of E&I (“Understanding and
addressing the epidemic of obesity: an energy balance
perspective,” J. Endocrine Review 2006;27:750.) Our cells
need E&I to communicate E&I and also to detoxify. If these
problems continue for very long, entire tissues (collections of
cells) and organs (collections of tissues) begin to malfunction.
Even our DNA runs on E&I (“Epigenetics a Window on Gene
Dysregulation, Disease,” JAMA 2008;299:1249.)
Simply stated, cell membranes are TOILing. This is why cells
cannot communicate E&I effectively, resulting in significant
deficiencies in E&I production and consumption. These are the
roots of all diseases.
Occam’s razor
Could it really be that simple? Stephen Wolfram’s book “A New
Kind of Science” (Wolfram Media, Inc, 2002) reassures us
that simple concepts underlie the seemingly complex vastness of
reality. The most complicated structures are born of simple
patterns that may easily be discerned by a well-programmed
computer. The J. Science agrees:
SEQ CHAPTER \h \r 1It is a mistake
to imagine that complex disease may not be solved by simple
approaches or that their causes are not simple. The grave danger
that terms such as ‘multi-factorial’ or ‘complex’ is that they
may justify the belief that solutions will come only from large
and expensive managed projects rather than from simpler
approaches ( SEQ CHAPTER \h \r 1“The
puzzle of complex diseases,” J. Science 2002;296.)
“Occam’s razor” is a physics principle that maintains
that “whenever one is confronted with many answers to a
problem, the simplest one is the correct one.” Sherlock
Holmes would agree. While it is true that we are likely to run
into “further light and knowledge” in the future and that
a true and rigorous scientific approach demands that we never
contemplate any answers as final, but mere approximations to
truth, the author agrees with Dr. Wolfram and many others who
feel that the final answers will involve light, or E&I.
Once we grasp that E&I are the foundations of the Universe, we
may see that environmental pollution is nothing more than
by-products of energy-making industries. The toxins or garbage
that industries produce are also called free radicals, or
oxidants. These environmental toxins are contributing to cell
membrane dysfunction. Remember the “T” in TOILing. Our
ability to detoxify them through our liver, kidneys, skin and
bowel detoxification pathways depends on good nutrition or E&I
to fuel those cells’ or organs’ function.
Solutions?
Our governments are having difficulties cleaning up our
environment. As problematic as pesticides, plastics, dioxin,
heavy metals, chlorinated and fluoridated compounds are, there
is something much more toxic in the environment: refined
sugars and transhydorgenated fats. Government
policies subsidizing crops like corn, wheat, and soy have
contributed to the flood of cheap, addicting foods that flood
our markets, and make fruits and vegetables les accessible. In
my opinion, the number one toxic agent contributing to cell
membrane break down of communication of E&I is the refined
garbage foods we eat.
The simple thermodynamic principles that govern the stars, the
atoms and our societies are also the reason why “food is the
best medicine.” If we change the way we eat, improve our
detoxification pathways (fix constipation, for example,) our “engine”
will work better and we will have better cell communication of
E&I and better health.
Some may say that our genes lock us into a hopeless “creation-destruction”
cycle that perpetuates poor regeneration of cells and tissues.
While this is true in rather rare diseases, it is not true for
the common chronic diseases that are ravaging our societies. In
other words, IR, diabetes, arthritis, high cholesterol, high
blood pressure, heart attacks, asthma, colitis, cancer,
Alzheimer’s Parkinson’s, etc., may be controlled and prevented
with diet. Genes are also influenced by E&I communication
principles. This is the message of hope in the new fields or “Nutrigenomics,
and Nutrigenetics” ““Nutragenomics, proteomics, and
metabolomics, and the practice of dietetics,” J. American
Dietetic Association 2006;25:1109; “Epigenetics at the
Epicenter of Modern Medicine,” JAMA 2008;299:1345.)
Let
us know consider not only the two most common problems our
patients have, fatigue and obesity, but practically all
diseases; E&I and TOILing are the root mechanisms involved, as
predicted by physicists like Dr. Deutsch (“The Fabric of
Reality,” Penguin Books, 1997.)
Dysmetabolic syndrome
The
clustering of diabetes, heart disease, obesity, high
cholesterol, abnormal clotting and elevated uric acid used to be
called “syndrome X” because we didn’t understand the common
denominator underlying these common conditions. That this
clustering is now called “dysmetabolic syndrome” is glaring
evidence that E&I problems in the form IR or TOILing are
involved. In other words, our metabolism is not optimal (AJCN
2005;82:497.) Let us review TOILing in more detail:
(1)
Cell Membrane Toxicity
Toxicity of the cell membrane is a concept generally ignored by
most docs, who argue that our kidneys, liver, skin and
intestines do a very good job of detoxifying. They argue that we
don’t need to fuzz about detoxification issues very much, unless
we are acutely toxic, like a chemical spill in your
neighborhood, or some industrial worker, who, after years of
battling the alleged offending employer, is told that his
disease “is all in his head.” In my opinion,
environmental toxins, or free radicals, and the oxidants we make
ourselves when we metabolize E&I are serious contributors to
cell membrane dysfunction, especially in those of us who have
genetic tendencies to detoxify less efficiently (“Persistent
Pollutants and the Burden of Diabetes” (J. Lancet
2006;368:558,)
Refined sugars and transhydrogenated fats are in my
opinion, the most serious toxins, since we consume them in high
quantities. Most of their damage takes place by substituting the
healthy sugars and fats on the cell membrane. Environmentalists,
as well intended as they are, are concentrating on a few
micrograms of toxin exposure, like air pollution, while ignoring
the kilograms of refined sugars and fats we eat on a daily
basis. They are not wrong. I agree with their concern: I am the
chairman of the Environmental/Public Health committee for the
Utah Medical Association. But, as a society, we don’t understand
the dramatic toxic effects refined sugars and fats have on cell
communication, E&I, and how aggressive we need to be to lick our
sugar addiction. Imagine what we could achieve if our “sweet
death” also became “an inconvenient truth” and got the
same type of coverage (“Sweet Death,” Rodier.
Soundconcepts Press, 2006.)
The
article “Persistent pollutants and the burden of diabetes”
(J. Lancet 2006;368:558) illustrates the issue of toxicity very
well. Here are the main points:
·
Dioxins, polychlorinated biphenyls,
dichlorophenyldichloroethylene from DDT/DDE, trans-nonachlor,
hexachlorobenzene, hexachlorociclohexanes, plus many other
chemicals, like phthalates in plastics are commonly found in
humans (“The Chemicas within Us,” J. National Geographics,
October 2006, page 116,)
·
A study analyzed these persistent organic solvents
and fasting plasma glucose concentrations in a random sample of
the general population, from 1999-2002 (“A strong
dose-response relation between serum concentrations of
persistent organic pollutants and diabetes,” J. Diabetes
Care 1996;29:1638.)
·
The prevalence of diabetes was 5 times higher in
groups with higher concentrations of these toxins. The
prevalence of diabetes doubled and tripled in the upper
quantiles of DDE and other compounds.
·
The body burden of these fat-soluble chemicals
often increases with increasing body-mass index. This means that
fat stores more toxins.
·
“Might diabetes cause a higher accumulation of
persistent organic pollutants?”
·
“People with diabetes would be more likely to
experience the adverse effects of these pollutants,” J.
Environmental Health Perspectives 2001;109:871
·
“There was no association between obesity and
diabetes in individuals with non-detectable levels of toxins.
Obesity was a risk factor for diabetes only if people had blood
concentrations of the pollutants above a certain level. This
finding might imply that virtually all the risk of diabetes
conferred by obesity is attributable to persistent organic
pollutants, and that obesity is only a vehicle for such
chemicals. This possibility is shocking.”
·
In a Michigan study, diabetes was associated with
PCBs. People with higher PCBs had twice the incidence of
diabetes, J. Epidemiology 2006;17:352
·
Conclusion: “The causal role of toxins in
diabetes is more likely to be contributory and indirect, i.e.,
through immunosuppressant, non-genotoxic, perhaps epigenetic
mechanisms.”
Toxins are also causing significant heart disease: traffic
pollution increases the risk of heart attacks (J. Occ Env Med
2006;63:844) and fine particulate exposure (PM 2.5) increases
hospital admissions for cardiovascular and respiratory problems
(JAMA 2006;295:1127.) Toxins cause TOILing of the endothelium
and also thyroid hormone dysfunction (“Environmental
chemicals and thyroid function,” European J.
Endocrinology 2006;154:599,) which in turn inflames our
endothelium even more (“Low grade systemic inflammation
causes endothelial dysfunction in patients with Hashimoto’s
thyroiditis,” J. Clin Endo Met 2006;91:5076,) elevates our
cholesterol levels and increases our risk of heart disease (Hypothyroidism
and atherosclerosis,” J. Clinical Endocrinology & Metabolism
2003;88:2438.
(2) Cell Membrane
Oxidation
Oxidation, which is very much like inflammation, is also
involved in the metabolic syndrome. Cell membrane oxidation
leads to IR and to all the complications we see in diabetics (J.
Diabetes/Metabolism Research and Reviews 2006;22:257) But, the
cell membrane is not the only thing TOILing: reactive oxygen
species found through blood testing also signals oxidative
stress in the pancreas which may lead to insulin secretion
problems (J. Diabetes 2007;56:1783.)
The article “Is oxidative stress the pathogenic mechanism
underlying IR, Diabetes and Cardiovascular disease? The common
soil hypothesis revisited” (J. Arteriosclerosis Thrombosis
Vascular Biology 2004;24:823) is an excellent review. The “common
soil” refers to the cells that make up our tissues. Whether
we are dealing with our heart, kidneys, brain, lungs, bones,
etc, these organs constitute a “common soil” with
identical needs for good E&I to live longer, avoid disease, and
avoid ending up like the “tinman” (“Mortality in
randomized trials of antioxidant supplementation for primary and
secondary prevention,” JAMA 2007;297:842.)
If
we are not consuming enough antioxidants in our diet, the
products of combustion in our cells (oxidants,) and the free
radicals we take in from combustion-processes in the environment
(pollution,) will scavenge the “common soil” looking for
electrons to satisfy their hunger for completion (JAMA
2007;297:842.) In the course of producing energy, they donated
an electron, which they now want to get back. Our cell membranes
making up our common terrain are the most accessible and
vulnerable to their predatory behavior. When free radicals
scavenge our cell membranes, TOILing begins, with dire
consequences to our cells ability to process E&I, and cell
communication. And, the more we get oxidized, the more fat we
accumulate (“Energy expenditure and substrate oxidation
predicts changes in body fat in children,” AJCN
2006;84:862.)
Here are the main points of the “common soil” article:
·
The endothelium, or lining of arteries is
oxidized, which leads to many diseases. Poor circulation of E&I
contributes to TOILing of our common soil.
·
Commonly used drugs for heart disease are really
antioxidants: calcium channel blockers like norvasc/amlodipine;
ACE inhibitors, like vasotec/ramipril; statins like lipitor/atorvastatin;
and PPAR, like avandia/rosiglitazone.
·
When caloric intake exceeds energy expenditure,
excess mitochondrial NADH ( a molecule in the Krebb’s cycle of
energy production,) and reactive oxygen species are generated.
To protect itself, the cell membrane develops IR.
·
Excessive NADH cannot be dissipated by
phosphorylation (the process of making energy in the
mitochondria:) more free radicals are formed.
·
Antioxidants decrease IR.
·
Same thing happens in beta cells: oxidative stress
reduces function.
·
High glucose induces mitochondrial reactive
species, leading to suppression of the first phase of insulin
secretion.
·
Glutathione (master antioxidant) potentiates
insulin secretion in patients with impaired glucose tolerance,
IGT, otherwise known as pre-diabetes.
·
Insulin-producing beta cells in the pancreas are
damaged by oxidative stress.
·
A single episode of hyperglycemia triggers
overproduction of super oxide dysmutase, SOD by mitochondria.
This causes nitrous oxide generation and then the formation of
peroxinitrates, which damage our DNA.
·
Hyperglycemia after meals is associated with
oxidative stress.
·
Mitochondrial overproduction of free radicals
impairs first phase of insulin secretion.
·
Hyperglycemia after meals is a better predictor of
cardiovascular complications than A1cHb, or the test called
Glycosylated hemoglobin.
·
Chronic inflammation is a manifestation of
oxidative stress.
C.O.P. stands for cholesterol oxidation products (British
J. Nutrition 2002;88:335.) The relationship between oxidized
cholesterol and heart disease is quite compelling (“Oxidative
stress and vascular disease,” J. Atherosclerosis Thrombosis
Vascular Biology 2005;25:29.) At the same time, the endothelium
is inflamed and oxidized, which makes the lining cells of the
endothelium become sticky. Cholesterol then readily sticks to
the arterial walls to initiate plaque formation (“Oxidized
LDL in plasma is a prognostic marker of subclinical
atherosclerosis development in clinically healthy men,” J.
Internal Medicine 2004;256:413.)
(3) Cell Membrane Inflammation
Diabetes is an inflammatory condition (“High glycemic
load increases C- Reactive Protein, an inflammatory marker in
the blood,” AJCN 2002;75:492.) The inflammation of
cell membrane receptors, and inflammatory messengers trigger
TOIling (J. Science 2003;300:1527,) making the cell membrane IR
(JAMA 2001;286:327.) Even before developing diabetes, we may see
that the higher the insulin levels, the higher the markers for
inflammation, and vice versa (J. Clinical Endocrinology &
Metabolism 2007;92:2041.)
Increased inflammatory messengers may even predict the risk of
future weight gain (J. Diabetes 2003;52:2097.) In other words,
obesity is also an inflammatory condition (J. Metabolism
Clinical and Experimental 2007;56:662.) The more fat tissue one
has, the more inflammatory messengers one releases. This is why
weight loss lowers inflammatory markers like CRP, with a
consequent reduction in IR (J. Arteriosclerosis, Thrombosis and
Vascular Biology 2003;23:1042.)
Chronic inflammation leads to
chronic IR (J. Current Opinion Clinical Nutrition Metabolic Care
2002;5:551.) The metabolic syndrome has also been associated
with inflammation (J. Circulation 2004;110:380.) This
inflammation causes the lining of arteries to put out messages
of distress, which lead to coagulation problems, such as clots
in legs. This is why obese people have more leg clots (J. Family
Practice News, March 2004, p11.)
We
know what is inflaming our cell membranes: diet, toxic
environments, and poor attitudes. The fact that fat tissues
store more toxins creates a vicious cycle, since environmental
toxins increase inflammation, and oxidation (see below.)
The
article “The energy request of inflammation” (J.
Endocrinology 2006;147:4550) makes the point that inflammatory
messengers like cytokines play a significant role in our
metabolism. Inflammation itself causes energy to be spent less
efficiently, which creates another vicious cycle. The same thing
happens with any inefficient engine. As it overheats, it
produces even more “inflammation,” which makes the engine
even more inefficient with time. An inflammatory response to
pathogens and toxins consumes large amounts of energy in our
body. The immune system at work puts a heavy load on our energy
metabolism. Think of fever. Our body responds to the
inflammation-triggered shortage of energy by allocating energy
where it is most needed, the immune system, and by turning down
the supply of energy where it is less needed (locomotion,
growth, and certain brain functions.) To respond quicker, the
uptake of glucose into immune system cells does not require
insulin.
The paper “Insulin
resistance (IR) and chronic cardiovascular inflammatory syndrome”
(J. Endocrine Reviews 2003;88:2399) ties together a lot of
related conditions through the mechanism of inflammation. For
instance, IR is the root of dysfunctional lipid metabolism. In
other words, IR interferes with the liver’s ability to handle
cholesterol properly.
IR begets inflammation and vice versa: “acute infections
cause IR and even after clinical recovery, some impairment in
carbohydrate metabolism persists.” Higher white blood cell
(WBC) counts are seen in IR. In fact, the highest quartile of
WBC had a 50% increased risk of diabetes. Aspirin, an
anti-inflammatory molecule, reduced glucose by 25%, CRP by 15%,
triglycerides by 50% and insulin clearance by 30%.
(4) Cell membrane and mitochondrial dysfunction:
“L,” or Lack of optimal mitochondrial function
E&I
from the Sun are processed in every cell of the body,
specifically in the mitochondria, which are cells themselves.
They maintain a symbiotic relationship with the systemic cells
they live in. Mitochondrial problems are the “L” in
TOILing, which also may stand for “Light,” or “Love,”
or “Less energy.” “Mitochondrial Medicine” (J.
Archives Neurology 2006;63:1505) is a book that summarizes how
practically all diseases have a degree of mitochondrial
dysfunction.
Each systemic cell has hundreds of mitochondria cells. The
systemic cells that need the most E&I, the heart, brain, and
muscles in general, have the most mitochondria cells to process
that E&I through the Krebb’s cycle of phosphorylation. This
cycle produces ATP (adenosine triphosphate) as a unit of energy.
Each mitochondria cell produces about 2 million ATP molecules,
which vibrate every one ten-thousandth of a second. Multiplying
this big number by 100 trillion (the number of cells we have in
our body,) gives us a number I am not sure my brain can
understand.
To
cope with less optimal E&I processing, the mitochondria may
undergo fusion, or fission, creating different arrangements in
mitochondria found in each systemic cell (“Mitochondrial
dynamics in disease,” NEJM 2007;356:1707.) Mitochondria are
very delicate, but they don’t seem to quit working all of a
sudden. While they do eventually die, like any other cell, they
slowly lose their ability to put out ATP, which leads to
fatigue, and the slow deterioration of function we see in
disease, and aging.
Unfortunately, the Chronic Fatigue Syndrome is not widely
accepted in medical circles, even though it is officially
recognized as an entity (British medial Journal 2007;335:411.)
The dearth of positive tests while working up fatigue leads some
doctors to conclude that “nothing is wrong with the patient, so,
they need Prozac.” If we had tests that easily and conveniently
assess mitochondrial function, if doctors understood the
concepts of E&I, TOILing and the role of nutrition, toxic
environments and the mind-body connection, many patients would
be helped with this condition.
Mitochondrial dysfunction
compromises the Psycho-Neuro-Immune-Endocrine network of
communication of E&I, which leads to obesity and diabetes (J.
Science 2005;307:38 & “Mitochondrial disease,” J. Lancet
2006;368:70.) IR is the mechanism involved, which explains why
our muscles, which have the most mitochondria, get infiltrated
by fat (AJCN 2007;85:662.)Another vicious cycle is at play here,
since fatty muscles won’t work as well, leading to fatigue, and
even less activity. This is another reason why incremental, or
gradient exercise helps fatigue issues (J. Royal Society
Medicine 2006;99:506,) and building up our muscles decreases
diabetic tendencies (J. Clinical Endocrinology & Metabolism
2007;92:880.)
Each messenger of cell communication requires its own private
docking site, or receptor. For example, insulin will only attach
to insulin receptors, and serotonin, to serotonin receptors,
much like a key in a specific lock. It turns out that these
receptors are really “gates” that require E&I to open and
close. In fact, these gates are much like “energy fields”
(J. Science 1998;282:642,) like you see in movies where a shield
of energy keeps the matinee idol from momentarily getting out of
the aliens’ prison. E&I are required to open these gates. The
mitochondria provide ATP to fuel this process. If this does not
happen efficiently, which is seen as the mitochondria age, we
develop IR and resistance to every other cell messenger as well
(J. Functional Medicine 2007;27#4.)
Scientists have been able to trace everyone’s mitochondrial DNA
clear back to one single woman in Africa. She was dubbed “Eve,”
because all humans descended from her. It turns out that the
genetics of “mitochondrial defects may play a role in the
metabolic syndrome” (JAMA 2004;292:2823.) Some families have
a mutation in their mitochondrial genes: children of type II
diabetics seem to end up with more IR in their muscle cells,
which show more oxidation in their mitochondria (J. Diabetes
2007;56:1376.) Even prediabetics show a significant decrease in
mitochondrial DNA (J. Diabetes Research & Clinical Practice
1998;42:161.)
Mitochondrial function may be impaired if we lack magnesium,
which is also observed in patients with IR. Some people genetics
are such that they cannot correct low magnesium levels in their
cells, unless CoQ10, an antioxidant crucial for mitochondrial
function, is supplemented along with magnesium (“Mitochondria
DNA mutations, oxidative stress, and apoptosis in mammalian
aging,” J. Science 2005;309:481.)
The
way we process E&I from solar E&I, or food, is influenced by
genetic tendencies that may be mitigated by the very food we eat
(“A cluster of metabolic defects caused by mutations in
mitochondrial tRNA,” J. Science 2004;306:1190.) According to
Nutrigenomics our genes are influenced by our diets, and so is
our mitochondrial function (J. Nutrition 2001;131:924.) And,
optimal mitochondrial function is crucial to avoid developing a
sluggish metabolism in our muscles, and IR (J. Diabetes
2004;53:2861.) The more antioxidants we consume, the better
mitochondrial function we have (“Mitochondrial medicine: a
metabolic perspective on the pathology of oxidative
phosphorylation disorders,” J. Cell Metabolism 2006;3:9.)
Mitchondria cell membrane function is altered by all the
artificial, transhydrogenated fats we eat in processed foods (J.
Lipids 1979;14:727.) About 12% of mitochondrial function is lost
when we eat those plasticized fats (J. Boll Soc Ital Biol Sper
1984;60:1029.)
The
article “Of the fit and the fat: mitochondrial abnormalities
and type II diabetes” (J. Clinical Endocrinology &
Metabolism 2007;92:1229, 1467) reviews the principles of cell
membrane dysfunction, so that we may understand why
energy-boosting antioxidants like ALA, and CoQ10 help decrease
IR (J. Metabolism 2001;50:868 & European J. Clinical Nutrition
2002;56:1137.) Other than the E&I of our thoughts, our spirits,
and our hearts, the E&I from our food serves to fuel the
mitochondria, to “power up” each cell, and thereby enable
said cells to carry out whatever their particular function may
be. Each cell’s DNA determines said function through E&I stored
in its genes. At the most basic level, sweet death is due to
poor mitochondrial function (“Mitochondrial Diabetes,” J.
Endocrinology Investigation 2002;25:477.)
TOILing factors interplay with one another
All
4 components of TOILing interplay with one another. For example,
oxidative/inflammatory damage to the mitochondria in nerve
tissues is a key element in diabetes, particularly in neuron
dysfunction, or neuropathy. This is likely due to a faulty
thermostat in the brain (J. Neurology Reviews 2005;13:1.)
Oxidation of mitochondria is also quite prevalent in
neurodegenerative diseases like Alzheimer’s and Parkinson’s
diseases (J. FASEB 2005;19:638.)
Refined diets are low in B complex vitamins, like folic acid,
which increases oxidation of our DNA, and our cell membranes
(British J. Nutrition 2007;97:855.) And, environmental toxins,
which deplete our supply of B complex vitamins, act like free
radicals or oxidants, scavenging cell membranes in our
mitochondrial and systemic cell membranes (“Neuroprotection
in Parkinson’s disease” (JAMA 2004;291:358.) The more we
lack antioxidants, particularly glutathione the more
atherosclerotic lesions we develop on our arterial walls (J.
Atherosclerosis Thrombosis Vascular Biology 2007;27:1375.)
A beer-belly: beyond cosmetics
An
overabundance of fat cells in the “spare tire” around our
waistline makes us secrete hormones and neuronal signals of cell
communication. These fat cells’ messengers are leptin
(which signals the brain to control appetite,) tumor growth
factor alpha, angiotensinogen (a hormone controlling blood
pressure in the kidneys,) adiponectin, and resistin.
The newest hormone secreted by the spare tire has been named
vistafin, and it is also associated with higher lipids,
inflammation (J. Clinical Endocrinology & Metabolism
2007;92:666,) and endothelian dysfunction in type II diabetes
(J. Metabolism Clinical and Experimental 2007;56:451.)
These hormones lead to IR and an inability to lose weight once
these fat cells accumulate in the midsection, like ring do
annually on the trunk of a tree (J. Annals Nutrition &
Metabolism 2007;2006;50:499.) V.A.T., visceral adipose tissue
is becoming an important reasons behind a dysfunctional
metabolism (J. Lancet 2002;359:46.) Here is another
vicious cycle: the bigger the beer-belly, the more disrupted our
metabolism is, since these hormones increase IR, and the more IR,
the bigger the belly. In other words, VAT increases TOIling,
specifically inflammation, which accelerates clogging of our
arteries, thus compromising transport of E&I (J. Circulation
2008:117:798.) Not coincidentally, complaints of fatigue are
often seen in patients with a significant VAT. Likely this is
due to poor processing of E&I and mechanical problems that lead
to sleep apnea and less physical activity.
All diseases have a metabolic component
Once we understand the importance of E&I and cell communication
in our anatomy and physiology, we become proponents of expanding
the narrow definition of the present metabolic syndrome
(diabetes, high blood pressure, high cholesterol, clotting
problems and elevated uric acid.) For instance, a urologist is
advocating for bladder problems and even prostate cancer to
become part of the metabolic syndrome (Annual Meeting American
Urology Association, Anaheim, 2007.)
Let
us now look at the most common diseases and see how E&I issues
are compromised by TOILing.
Kidneys/urinary system
Chronic renal problems are often seen in people with the
metabolic syndrome (J. Mayo Clinic Proceedings 2007;82:822,) and
visceral fat increases the risk of renal disease in diabetics
(J. Family Practice News, February 1st, 2007, page
17.) IR worsens the risk of vascular injury in patients
undergoing hemodialysis for renal failure (J. Metabolism
Clinical and Experimental 2007;56:153.) Obesity, which is a
cousin of IR, decreases kidney function in kids (Annual Meeting
American College of Nutrition, Reno, 2007.)
If IR is present, we may deduce that
TOILing of cell membranes is at work:
T for toxicity: NEJM 2003;348:277
O for oxidation: Am J. Kidney
Diseases 2006;48:752
I for inflammation: Am J.
Clinical Nutrition 2005;82:342
L for less mitochondrial function: J.
Archives Neurology 2006;63:1505
Hormones
“Metabolic syndrome and the endocrine
stress system,”
J. Hormone Metabolism Research
2006;38:437
T: JAMA 2005;294:291
O: J. Cancer Research
1998;58:2269
I:
J. Nat’l Cancer Institute 2003;31:29
L: J. Cell
Metabolism 2006;3:9
Cancer
“Cancer’s sweet tooth: the Janus
effect of glucose metabolism in
tumorigenesis,”
J. Lancet 2006;367:618
T: New England J. of Medicine
2000;343:78
O: J. Carcinogenesis 2006;27:240
I: J. Lancet 2001;357:539
L: J.
Carcinogenesis 2007;28:233
Neurological diseases
“Neuroprotection in Parkinson’s
Disease,” JAMA 2004;291:358
T: J. Lancet 2006;368:2167
O: J. Endocrinology Reviews
2007;148:548
I: JAMA 2004;292:2237
L: JAMA 2004;291:679
Intestinal diseases
“Metabolic learning in the
intestines: adaptation to nutrition and
luminal factors,” J.
Hormone Metabolism Research 2006;38:452
T: J. Gut 2001;48:503
O: J. Digestive Diseases and Science
2006;51:488
I:
J. Gastroenterology 2006;41:10
L: . J. Lipids
2002;37:193
Bone/arthritic problems
“Gut-joint
axis: cross reactive food antibodies in rheumatoid
arthritis,” J.
Gut 2006;55:1240
T: J. Trends in Immunology, July
2006, volume 27
O:
J. Rheumatology 2002;29:2271
I: J.
Rheumatology 2002;29:1
L: J.
Toxicology Letters 2003;140:113.
Genetics
The new fields of
Nutrigenomics and Nutrigenetics have shown that E&I and
genetic TOILing are critical in determining the proper
translation and manifestation of genetic information (J.
American Dietetic Association 2006;25:1109.)
Solutions
“As more and more Americans are afflicted with chronic
diseases in which nutrition plays a key role, the
need for improved nutrition training of physicians has never
been more evident… Even though medical technology continues to
make advances in the pharmacologic and surgical management of
these chronic diseases, the evidence is that much of the
morbidity and mortality associated with these
conditions may be preventable through dietary and lifestyle
modifications” (“An evidence-based approach to
medical nutrition education,” AJCN
2006;83(supp):929s.)
The Mediterranean diet should be our goal: whole grains,
olives, nuts, fish, fruits, vegetables, lemons, garlic, onions,
cruciferous, lean meat and wine. By eating this well, people
70-90 years old have a 50% reduction in mortality (“Mediterranean
diet, lifestyle factors and 10 year mortality in elderly
European men and women,” JAMA 2004;292:1433.) The E&I
contained in this diet helps reduce TOILing and thus improve
cell communication of that very E&I.
In my clinical experience, about 80% of prescription drugs are
discontinued when patients comply with TLC, Therapeutic
Lifestyles Changes. In my opinion, doctors do best to become
teachers and motivators to emphasize food as the best medicine.
The following articles are a small sample of the many studies
that have been published showing how nutrition (E&I) has
dramatic effects on the diseases mentioned above:
“Diet-induced leptin resistance: the heart of the matter”
J. Endocrinology 2007;148:921
“Hormones and recalcitrant obesity”
American Society of Bariatric Physicians Symposium,
San Diego, 2006,
J. Family Practice News, January 1st,
2007, page 34
“The metabolic syndrome in PCOS”
J. Endocrinology 2006;29:270
“Thyroid function is intrinsically linked to insulin
sensitivity and endothelium dependent vasodilatation in healthy
euthyroid subjects”
J. Clinical Endocrinology & Metabolism 2006;91:3337
“Plasma Ghrelin, obesity and the PCOS: correlation with
Insulin resistance and androgen levels”
J. Clinical Endocrinology Metabolism 2002;87:5625
“Sex hormones, inflammation and the metabolic syndrome”
European J. Endocrinology 2003;149:601
“Metabolic
targeting as an anticancer strategy: dawn of a new era?”
J. Science 2007;316:1
“Prostate cancer prevention by nutritional means to alleviate
metabolic syndrome” AJCN 2007;86:889S
“Apoptosis
(cell death) by dietary factors”
J. Carcinogenesis 2007;28:233
“Impaired
insulin and insulin like growth factor expression and signaling
mechanisms in AD: is this type III diabetes?”
J. Alzheimer’s Disease 2005;7:63
“The
metabolic syndrome, inflammation, and risk of cognitive decline”
JAMA 2004;292:2237
“High glucose induce oxidative stress and mitochondrial
dysfunction in neurons” FASEB J. 2002;16:1738
“Outcome-based
comparison of ritalin versus food-supplement treated children
with AD/HD”
J. Alternative Medicine Review, 2003;8:319
“The
metabolic anatomy of Tourette’s syndrome”
J. Neurology 1997;48:927
“Diet and Lifestyle interventions lower risk of dementia”
Alzheimer’s Association International Conference on
Preventing Dementia, Washington, D.C., 2005.
“The metabolic syndrome and preventive cardiology: working
together to reduce cardiometabolic risks”
J. Metabolic Syndrome and Related Disorders
2006;4:233
“Type
2 diabetes and heart disease: all roads lead to insulin
signaling”
J. Townsend Letter, May 2007, page 72
“Diabetes
and cardiovascular disease and common soil hypothesis”
J. Diabetes 1995;44:369
“Attacking
the metabolic syndrome to reduce atherosclerotic risk”
J. Cardiology Review 2002;19:supp13
“Is oxidative stress the pathogenic mechanism underlying
insulin resistance, Diabetes and Cardiovascular disease? The
common soil hypothesis revisited”
J. Arteriosclerosis Thrombosis Vascular Biology
2004;24:823
“Fatty acid, dyslipidemia and insulin resistance”
J. Royal Society of Medicine 2002;96:symposium
“Mechanisms by which dietary fatty acids modulate plasma
lipids”
J. Nutrition 2005;135:2075
“Associations between depressive symptoms and insulin
resistance”
J. Diabetologia 2006;49:2974
“Metabolic syndrome in women with chronic pain”
J. Metabolism Clinical and Experimental 2007;56:87
“Insulin Resistance in Rheumatoid Arthritis underlies
cardiovascular risk”
Annual Meeting British Society for Rheumatology,
Glasgow, 2006
“The
gut in ankylosing spondylitis and other arthropathies:
inflammation beneath the surface”
J. Rheumatology 2003;30:11
“Gut-joint
axis: cross reactive food antibodies in rheumatoid arthritis”
J. Gut 2006;55:1240
“A
vegan diet free of gluten improves the signs and symptoms of
rheumatoid arthritis: the effects on arthritis correlate with a
reduction in antibodies to food allergens”
J. Rheumatology 2001;40:1175
“Acne
vulgaris: a disease of western civilizatio.”
J. Archives Dermatology 2002;138:1584
“Dietary
treatment of diabetes mellitus in the pre-insulin era”
J. Perspectives Biology Medicine 2006;49:77
“Effect
of weight loss with lifestyle intervention on risk of diabetes”
J. Diabetes Care 2006;29:2102
“Nutrigenomics
and metabolomics will change clinical nutrition and public
health practice”
AJCN 2007;86:542
“Effect
of a Mediterranean-style diet on endothelial dysfunction and
markers of vascular inflammation in the metabolic syndrome”
JAMA 2004;292:1440
“Guar Gum: a
miracle therapy for hypercholesterolemia, hyperglycemia and
obesity”
J.
Clinical Reviews in Food Science and Nutrition 2007;47:389
“Insoluble
cereal fiber reduces appetite and short term food intake and
glycemic response to food consumed 75 minutes later”
AJCN
2007;86:972
Fifth International
Symposium on the role of Soy in Preventing and Treating Chronic
Disease”
Orlando, Florida,
2003. Loma Linda University. Published in J. Nutrition
2004;134:1205s
“Glycosylation and the immune system”
J. Science 2001;291:2370-2375
“Omega
Fatty acids: recommendations for therapeutics and prevention”
AJCN 2006;83#6s
Fortunately, the National Institute of Health is allotting more
funds for nutritional research than any other field of endeavor.
This will continue to fuel the explosion of interest we are
seeing in this arena: 122 grants went to nutrition-related
investigations, out of 236 grants in 2007 (http://nccam.nih.gov/research/extramural/awards/2007.)
In concluding I quote from two
outstanding articles:
“What is nutrition?” (AJCN 2003;77:149)
“All physicians are involved with nutrition, for it is not
the disease that is important, but the person who has the
disease, and each person is the product of his nutrition.”
“What is nutrition? It is the cornerstone of preventive
medicine, the handmaiden of curative medicine and the
responsibility of every physician.”
“Nutrition guidance of Family Doctors towards best practice,”
Proceedings of the Third Heelsum International Workshop,
Netherlands, December 2001
“It is
essential that practicing physicians develop a working knowledge
of herbs and stay abreast of these emerging findings in order to
best advise their patients on the value of health promoting
diets in disease and prevention.”
“These are heady days for nutritional scientists as
newer understandings of food and health promise to bring
clinical nutrition to the forefront of clinical medicine.
Practitioners must become nutritionally educated and oriented if
they are to maintain their patients’ confidence and stay abreast
of this aspect of continuously evolving modern medicine” (AJCN
2003;77:1001S.)
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