This disease, so frequently
attending all long voyages, and so particularly destructive to
us, is surely the most singular and unaccountable of any that
affects the human body. For its symptoms are inconstant and innumerable,
and its progress and effects extremely irregular: for scarcely
two persons have the same complaints, and where there is found
some conformity in symptoms, the order of their appearance has
been totally different. However, though it frequently puts on
the form of many other diseases, and is therefore not to be described
by any exclusive and infallible criterions.
Chaplain Richard Walter
Anson's Voyages Around the World in the
The link between nutrient
deficiency and the "inconstant and innumerable symptoms"
was not understood when the above observation of scurvy was penned.
Two centuries later, Roger Williams, the discoverer of pantothenic
acid (vitamin B5), described biochemical individuality and the genetotrophic
theory of disease. Nutritional deficiencies, he observed, are expressed
differently among individuals, both in symptoms and in the order
they appear, based upon the impact of environmental inputs on individual
biochemistry and genetics.
Science has advanced appreciably since that well-controlled but
unintentional experiment that place groups of individuals on boats
and systematically deprived them of a particular nutrient over an
extended period of time. We know a lot about how nutrients function,
the roles they play in the health of different organ systems, and
the symptoms and diseases of nutrient deficiency. This knowledge
has virtually eradicated nutrient deficiency diseases from countries
with adequate food supply and fortification. As a result, the convention
in medicine is that, so long as we get the Recommended Daily Allowance
(RDA) levels in our diets (and there is a basic assumption that
most of us do), nutrition is not a significant factor in most diseases
we see today. Doctors diagnose the diverse symptoms that patients
bring to the doctor's office as disparate diseases, often using
diagnostic laboratory test results to identify a marker for organ
malfunction or failure. Therapy often involves pharmaceutical and
surgical intervention to reduce symptoms.
and Functional Medicine Approach
Patients come to Integrative and Functional Medicine (IFM) clinicians
with a variety of complex, chronic symptoms and diseases. Drugs
or surgery may not have worked for them or may even have made them
worse. They may be part of a growing number of individuals with
an aversion to covering up symptoms with medications or cutting
out a misbehaving organ. They may want a truly integrative treatment
that combines the best of conventional and IFM treatments. The IFM
clinician looks for suboptimal nutrient status that can adversely
affect function, or nutrient insufficiency, that underlies many
complex, chronic diseases. Initial conditions of insufficiency are
seen at a biochemical level without symptoms. As the duration of
the insufficiency increases, additional changes appear in cellular
function that can be seen as subclinical manifestations, such as
behavioral and mental/emotional instabilities and other symptoms.
As the insufficiency progresses into later stages, morphological
and functional changes occur that can be defined as the early stage
of disease. Finally, diagnosed pathology is expressed with end organ
failure and ultimately death. (Figure 1).
Because essential nutrients play fundamental roles in cellular metabolism,
as insufficiencies develop, the effects can be system-wide. Variation
in disease expression is exponentially compounded when multiple
nutrient deficiencies are involved, which is often the case in complex,
chronic diseases. Any and every aspect of body function can potentially
become compromised, making it difficult to determine the type and
quantity of a needed nutrient by studying symptoms alone.
The IFM clinician does not treat fibromyalgia, chronic fatigue,
and inflammatory bowel; rather, the clinician treats the individual
nutritional insufficiencies, metabolic imbalances, and toxicities
that prevent normal function and are expressed in each person as
a different set of symptoms. Once corrected, symptoms are mitigated,
just as the various expressions of vitamin C deficiency in scurvy
are reversed once the patient is replete in the vitamin. Similarly,
B-vitamin insufficiencies can be seen in many different symptoms
related to energy metabolism and mitochondrial efficiency. Supplementation
of these nutrients to ameliorate metabolic disorders has been well
documented.1 Another example is toxic lead exposure, which may be
expressed in some individuals as inflammatory disorders, in others
as immune disorders, and still others as neurological disorders.2,3
Many factors influence nutrient status in the individual (Figure
2), such as diet, digestion, absorption, disease states,
age, medications, stress, toxic exposures, activity levels, genetics,
and biological differences. The IFM practitioner takes into consideration
this full range of factors that can be affecting patient symptoms
and uses laboratory assessments to fine-tune treatment.
with Laboratory Tests
Protocol-driven nutritional regimens based upon symptoms have been
the major approach in IFM for decades. Supplement companies continue
to develop products to treat specific symptoms. This approach is
limited, since two individuals can present with the same symptoms
but resulting from two different causes, and the same underlying
mechanisms in two patients can result in different symptoms in each
patient. Clinicians relying on protocols recommend supplements and
dosages that may not address underlying issues. The clinical laboratory
provides valuable information for targeted therapy based upon the
biochemical individuality of the patient.
Many IFM laboratory tests are not used to diagnose disease since
patients with different symptoms may have very similar metabolic
profiles. Familiar diagnostic tests (fasting blood glucose, elevated
serum PSA, and elevated white blood cells, etc.) help to put labels
on diseases. But is there a metabolic, nutritional, or toxicity
pattern to fibromyalgia that would distinguish it from chronic fatigue
or autistic spectrum disorders – or even cardiovascular disease?
Decades of experience with nutritional and metabolic profiling call
into question the value of attempting to diagnose many complex chronic
diseases by laboratory test results. However, they can be extremely
useful in targeting underlying mechanisms and guiding therapy.
What tests provide the most useful information for treating the
types of patients that come to the IFM practitioner? Obviously,
the "serum chemistry" of conventional care is not the
answer. That test was developed as a tool to screen for a variety
of conditions involving serious biochemical or physiological imbalances
associated with end-stage pathology. More often than not, patients
come to their IFM doctor with test results in hand that indicate
they are perfectly "normal" and wonder why they feel so
bad. Doctors look to the laboratory for more relevant tests to help
guide the types of therapies in the IFM arsenal. Should I modify
the diet and, if so, how? Does the patient need nutrient supplementation
and, if so, how much and what type? Is detoxification in order and,
if so, what regimen?
Organic Acid Profiling
– The "Basic Chemistry" for IFM
Of all the tests currently offered by IFM laboratories, the quantitative
organic acid profile is emerging as the basic chemistry profile
for IFM. Qualitative screening for organic acids has been used for
decades to detect neonatal inborn errors of metabolism – metabolic
defects that respond to specific cofactor supplementation. Quantitation
of these metabolites at lower levels was first offered to IFM practitioners
by Metametrix Clinical Laboratory in 1992 to detect more subtle
inefficiencies in enzyme function. Using an overnight urine collection,
the organic acid profile assesses a broad variety of nutritional
and metabolic issues that can directly affect patient care, including
· Carnitine insufficiency
· Need for B-complex vitamins, including specific markers
for biotin, folate, B12, B6, and lipoic acid
· Methylation status
· Mitochondrial function and need for coenzyme Q10
· Neurotransmitter metabolism
· Detoxification status
· Oxidant stress status
· Glutathione sufficiency
· Microbial compounds whose presence indicates potential
No other single test profile provides
such a broad array of information that can be used to identify and
treat nutritional insufficiencies, metabolic imbalances, and toxicities.
This is why many IFM practitioners are more commonly using this
test profile to help decipher the complex maze of symptoms they
see every day. As a result, more IFM laboratories have recognized
the profile's value and added it to their testing menus.
A 73-year-old woman who had been relatively healthy her entire life
recently developed a raised, hot and itchy rash on parts of her
body. She had been to several doctors with no relief. She sought
the advice of an IFM practitioner, who ordered the organic acid
comprehensive profile as a "basic chemistry." The test
results indicated she had an excessive amount of ammonia production.
Bacterial overgrowth in the intestines can produce large amounts
of ammonia that is absorbed into the system and can cause systemic
reactions. There were a number of elevated dysbiosis markers in
the profile, indicating this may be a causative factor. In addition,
there was an up-regulation of glutathione production and a significant
depletion of sulfate, which is critical for detoxification. These
findings indicated her detoxification systems were under severe
stress. The functional markers for B-complex vitamins, including
lipoic acid, were elevated, indicating insufficiency. Co-enzyme
Q10 markers indicated insufficiency of this critical nutrient. Treatment
included N-acetylcysteine, lipoic acid, and silymarin for liver
support; B-complex and co-enzyme Q10 to improve mitochondrial function;
and a bowel detoxification program to normalize bowel flora. Her
rash completely resolved in one month and had not recurred by her
four-month, follow-up visit.
It is understandable that the conventional approach to diagnosis
and treatment would not have resolved her symptoms. Even an IFM
protocol-driven approach might have failed to uncover the complex
mechanisms underlying her rash. The organic acid profile provided
targeted information for this non-intuitive, comprehensive treatment
plan that resulted in positive patient outcome.
The use of laboratory assessments can significantly assist the IFM
practitioner in improving patient outcome. Organic Acid Profiling
is proving to be a popular and useful clinical tool for routine
screening of the IFM patient, providing a wide array of information
in one test. Combination profiles for assessing not only organic
acids but amino and fatty acids and other nutrients are also available.
Supplement companies are also beginning to develop personalized
supplements based on test results rather than protocols. This "Test,
Don't Guess" approach replaces the older, protocol-driven,
"shotgun" approach with targeted, personalized therapies
based upon biochemical individuality. Because nutrient deficiencies,
metabolic disturbances, and toxicities can express differently in
individuals, based on their unique environmental, biochemical, and
genetic make-up, a strategy that targets the underlying disturbances
can improve patient outcome in a wide variety of diseases.
J. Alexander Bralley, PhD
3425 Corporate Way
Duluth, Georgia 30096
800-221-4640 / 770-446-5483
1. Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy
stimulates variant enzymes with decreased coenzyme binding affinity
(increased K[m]): Relevance to genetic disease and polymorphisms.
Am J Clin Nutr.
2. Milanov I, Kolev P. Clinical and electromyographic examinations
of patients with tremor after chronic occupational lead exposure.
Occup Med (Lond).
3. Hwang YF, et al. Chronic industrial exposure to lead in 63 subjects:
Clinical and erythrokinetic findings. Southeast
Asian J Trop Med Public Health.