. .

INDIVIDUAL OPTIMAL NUTRITION TM

Patient Guide
This ION™ Patient Guide is designed to help you better understand your laboratory test results.
The patterns of low, normal, or high results provide a unique view of the inner functioning of
your body.

This booklet contains the following sections:

• Introduction

• The ION™ Profile and Your Nutritional Needs

• Glossary

• Figure of Central Energy Pathways

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 Introduction
In the time it takes you to read this sentence, your amazing body
will have analyzed, synthesized, restructured, and utilized thousands
of nutrient molecules. It will have split proteins, burned sugars,
pumped minerals, exchanged gases, and transferred electrons.

Thousands of chemical reactions occur each second in your body,

every second of your life. Just imagine the energy required to
perform this biochemical magic that powers your human machine!

Where does your body get this energy? The foods you eat provide
fuel for your body. The nutrients you consume each day are your
body’s only source of raw materials. Each chemical reaction occurs
in a step-wise sequence and depends on the daily availability of raw
materials. A shortage of any nutrient can shut down the “assembly
lines” that are your body’s biochemical pathways.

Your body is amazingly adaptive and can sometimes function for

long periods of time even though particular biochemical “assembly
lines” are closed down. Eventually, however, certain nagging
symptoms can progress to become diseases that can destroy the
quality of life or even life itself.

The proteins, fats, and carbohydrates that you eat are fuel for your
physical engine. The vitamins and minerals are its spark plugs. You
need both high quality fuel and the ability to “fire on all cylinders”
in order to achieve optimal health. An automobile can run with
misfiring spark plugs, but for how long and how well? How fast and
efficiently can it respond to an emergency demand for more power?
The stress of living in our fast-paced world demands that kind of
emergency power for our bodies on a daily basis.

Think of other nutrients as protecting agents. Just as your car has

additives and devices that protect the body, engine, and driver,
nutrients serve to protect your heart, brain, and other critical organs.
Just as a car’s gauges warn the driver of potential problems, your
body has certain chemical indicators that can alert you to potential
problems. Early warnings can help you make diet and lifestyle
changes that may both extend your life and enhance your quality of
life.

Modern laboratory methods let us measure essential vitamins,

minerals, amino acids, and fatty acids to see if your body has
adequate reserves to meet the demands of your lifestyle and to
support your tissue needs for healing. We also look for the presence
of specific “marker” chemicals that signal special needs or dangers.
For example, methylmalonate is a vitamin B12 marker. If you have
 a vitamin B12 deficiency, methylmalonate levels rise because the vitamin B12-dependent reaction that converts
methylmalonate is inhibited. In this case, you may need vitamin B12 supplements to maintain the health and
proper function of your body. In addition to nutrient markers, we also measure markers that assess intestinal
health, neurotransmitter activity, and detoxification demands.

No two people are exactly alike. In addition to your unique outward appearance, the way that your body functions
inside is very much dependent on your individual genetic and environmental influences. You have special needs
for dietary nutrients that maintain healthy tissues and fight the processes of disease, degeneration, and accelerated
aging. Some people need certain nutrients many times higher than the “normal” dietary intake to allow for the
restoration of health. If you don’t need them, however, using very high doses of nutrient supplements can cause
other imbalances.

The ION™ Profile shows your special needs by combining information from measurements of nutrients and
nutrient marker compounds. The laboratory tests performed on your specimens include:

• Amino acids in blood plasma • Lipid peroxides in blood serum

• Homocysteine in blood serum • Fatty acids in blood plasma
• Mineral (Element) analysis in red blood cells • Organic acids in urine
• Fat-soluble vitamins in blood serum

To help you understand how your recommendations were created, this booklet is organized by nutrient category
to show how each component of the ION Profile relates to your nutrient status. Your special needs for vitamins,
minerals, amino acids, fatty acids, and antioxidants are determined by grouping together all of the test results
that indicate your need for supplementation. The recommendations are adjusted according to the significance of
nutrient marker levels. There are many areas of overlap and cross-correlations among the data, showing the value
of this integrated set of laboratory tests. Your healthcare provider, with full knowledge of your medical history and
concerns, can use this information to provide an optimal nutritional support program for you.

2.
The ION™ Profile and Your Nutritional Needs
The paragraphs that follow explain the importance of measured compounds (shown in red) to your biochemistry and
health. Each compound reveals your areas of internal strengths and weaknesses and your need for specific nutrients.
For each area discussed, you will find one or two representative references from the hundreds of pertinent studies in the
scientific literature.

Vitamins
Vitamins are compounds that your body must have to be healthy. Vitamins are “essential” for proper function, which
means that they are not made inside your body and must be consumed in the diet. Your body needs vitamins for many
reasons. Without them, organs cannot function properly, skin ages rapidly, and vision fails.

Antioxidant Vitamins

Vitamins A, C, and E and the nutrients beta-carotene and coenzyme Q10 are grouped together because they are all involved
in antioxidant protection. The principal membrane antioxidant is vitamin E. The Lipid peroxide and 8-Hydroxy-2’-
deoxyguanosine levels included in the ION profile are indicators of how much damage your body may be sustaining due
to lack of antioxidant protection. Antioxidant deficiency accelerates the process of aging and the risk of developing chronic
diseases.

Vitamin A

Every day you lose some vitamin A because it is used in the replacement of old tissues. Vitamin A is an antioxidant in the
membranes of your cells where it serves a protective function. Vitamin A is required by the eye for vision, and it also is needed
to protect the rest of your body from damaging effects of infection and stress. However, too much vitamin A can be dangerous,
particularly during pregnancy. If your levels are too high, the recommended intake range will be zero. Beta-carotene also
protects tissue, your body converts it on an as-needed basis, and so supplementation with beta-carotene is a safer alternative
than with vitamin A. Lipid peroxides indicate damage to cell membranes from oxidation. 8-Hydroxy-2’-deoxyguanosine
measures the oxidative impact to DNA. The lipid peroxide and 8-Hydroxy-2’-deoxyguanosine levels will be high if your total
antioxidant protection is inadequate. If these markers are high and vitamin A is normal, then either you need other specific
antioxidants (see below) or you have a high rate of free radical oxidant production.

Vitamin C

Vitamin C is easily lost from the body and must be replaced frequently. Most experts agree that the average healthy person
needs a minimum of 100-150 mg of vitamin C per day to stay healthy. Diseases and other stresses increase your need for
vitamin C. Inadequate vitamin C is one factor leading to elevated Lipid peroxide. Elevated 8-Hydroxy-2’-deoxyguanosine
indicates oxidation and need for vitamin C protection. Extra vitamin C is one way to combat the effects of elevated blood levels
of toxic heavy metals like Mercury, Cadmium, or Lead. If the cell regulator that uses vitamin C (p-Hydroxyphenyllactate) is
high, you may need much higher vitamin C intake (up to bowel tolerance doses) to restore normal metabolism and cell control.
You will notice that we did not measure vitamin C directly since vitamin C degrades very rapidly and therefore cannot be
measured accurately in a blood specimen sent to the laboratory.

Vitamin E

Vitamin E is a major part of your protection from daily wear and tear. It works to remove harmful molecules that degrade the
fatty acids that make up cell membranes (i.e., arachidonic acid). Conditions that increase oxidative metabolism tend to raise
your requirements for vitamin E. High levels of p-Hydroxyphenyllactate, 8-Hydroxy-2’-deoxyguanosine, and Quinolinate
are associated with increased oxidative stress. Significant elevations in one or more of these compounds could indicate a strong
need for other antioxidants as well. The amount of vitamin E that is best for you, again, is influenced by the results of your
Lipid peroxide test and your serum Vitamin E levels.

3.
 Yang, C.S., Chen, W.Y., et al., Alpha-tocopherol acetate significantly suppressed the increase in heart interstitial 8-hydroxydeoxyguanosine
following myocardial ischemia and reperfusion in anesthetized rats. Clin Chim Acta, 1999. 285(1-2): 163-8.

Rabinoff, M., Short note: possible role of macrophage metabolic products including quinolinic acid and neopterin in the pathogenesis of
inflammatory brain diseases. Med Hypotheses, 1994. 42(2): 133-4.

Markaverich, B. M., R. R. Gregory, et al. (1990). Methyl p-Hydroxyphenyllactate and nuclear type II binding sites in malignant cells: metabolic
fate and mammary tumor growth. Cancer Res, 50(5): 1470-8.

Raushenbakh, M. O., V. D. Ivanova, et al. (1982). [Effect of ascorbic acid on the formation and leukemogenic action of p-hydroxyphenyl-lactic
acid]. Probl Gematol Pereliv Krovi, 27(7): 3-6.

Coenzyme Q10

Since your body can make Coenzyme Q10, it is not called a vitamin. If you are making enough to meet the demands of
your tissues, you do not need to take any extra. However, many people do not make enough coenzyme Q10. Certain drugs
have also been shown to block coenzyme Q10 production. Elevated Lipid peroxides may indicate a need for coenzyme Q10.
High Hydroxymethylglutarate can reveal a block in your body’s synthesis of coenzyme Q10. Other functional markers such
as Lactate, Succinate, Fumarate, and Malate indicate whether your body is able to produce energy efficiently by utilizing
coenzyme Q10.

Goli, A.K., Goli, S.A., et al., Simvastatin-induced lactic acidosis: a rare adverse reaction? Clin Pharmacol Ther, 2002. 72(4): 461-4.

B-Complex Vitamins

The B-complex vitamins are necessary for many enzymes in your body to function properly. Your body uses enzymes to
extract energy from food, build new tissue, remove toxins, and maintain the immune system.

Vitamin B1, B3 and, B5

Vitamins B1 (thiamin), B3 (niacin), and B5 (pantothenic acid) are some of the most easily lost vitamins. All kinds of stressors,
both emotional and physical, can increase losses of B vitamins. Vitamins B1, B3, and B5 are necessary for energy pathways of
all of the cells in your body. As your food is broken down and metabolized, specific compounds are formed from biochemical
steps that require B vitamin assistance. Such steps occur in carbohydrate breakdown where Pyruvate and Lactate are formed.
Amino acids form α-Ketoisovalerate, α-Ketoisocaproate, and α-Keto-ß-Methylvalerate, which require B vitamins for further
breakdown. Carbohydrates and amino acids share a common B-vitamin-dependent step where α-Ketoglutarate is formed
(Figure 1). If you have a pattern of high levels of these compounds, you may need increased intake of vitamins B1, B3, and B5.
α-Hydroxybutyrate is another metabolic marker that is related to vitamin B3. The main reason for high α-Hydroxybutyrate is
an oxygen utilization problem that results in niacin getting stuck in a form called NADH. This blockage may be relieved by extra
vitamin B3, by increasing oxygen flow (exercise) or by decreasing intake of alcohol and simple sugars that place heavy demands
on the requirement for niacin.

Chuang, D.T., L.S. Ku, and R.P. Cox, Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-
keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate. Proc Natl Acad Sci USA, 1982. 79(10): 3300-4.

Vitamin B2

Dietary fat, carbohydrate, and protein are all broken down to produce energy using pathways that require vitamin B2
(riboflavin). If you do not have sufficient riboflavin, compounds such as Succinate, Adipate, Suberate, and Ethylmalonate are
found high in urine. Some of these compounds also give information about other micronutrients that are discussed below.

Yoon, H. R., S. H. Hahn, et al. (2001). Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin.
J Inherit Metab Dis 24(8): 870-3.

Elias, E., R. G. Gray, et al. (1997). Ethylmalonic adipic aciduria--a treatable hepatomuscular disorder in two adult brothers. J Hepatol
6(2): 433-6.

4.
Vitamin B6

Your body needs vitamin B6 (pyridoxine) to utilize amino acids

derived from dietary protein. Inadequate vitamin B6 is one
factor that leads to increased concentrations of Kynurenate
and Xanthurenate in urine. These products of amino acid
breakdown cannot be further metabolized in the absence of
vitamin B6. Abnormal levels of kynurenate can have direct effects
on brain function in addition to showing a need for vitamin
B6. Glutamine, Isoleucine, and Leucine are other amino acids
that serve as marker compounds for vitamin B6. Deficiency of
vitamin B6 can result in high levels of these amino acids. Vitamin
B6 deficiency may also result in elevated concentrations of
Homocysteine in blood, which leads to increased risk of heart
disease.

Takeuchi, F., Tsabouchi, R., et al., Kynurenine metabolism and xanthurenic acid formation in vitamin B6-deficient rat after tryptophan
injection. J Nutr Sci Vitaminol (Tokyo), 1989. 35(2): 111-22.

Vitamin B12 and Folic Acid

The most common dietary deficiency leading to homocysteine elevation and the associated increase in heart disease risk
involves vitamin B12 and folic acid. You can have normal blood levels of these vitamins but still not have enough for your
body’s enzymes to function properly. Dietary deficiency of vitamin B12 and folic acid are associated with increased risk of many
diseases, including anemia and the associated chronic fatigue. Methylmalonate is a sensitive functional marker for vitamin
B12; high levels of methylmalonate indicate vitamin B12 deficiency. The odd numbered fatty acids containing 15, 17, 19, or 21
carbon atoms (Heptadecanoic acid, Nonadecanoic acid, Tricosanoic acid, Pentadecanoic acid) accumulate in vitamin B12
deficiency. Formiminoglutamate (abbreviated FIGLU) is a compound made from the amino acid histidine. Insufficiency of
folic acid leads to high urinary FIGLU. Folic acid is especially critical for prenatal and childhood development. It is important
for lowering your risk of cardiovascular disease and cancer.

Shinka, T., Y. Inoue, et al. (2002). Two cases of benign methylmalonic aciduria detected during a pilot study of neonatal urine screening.
J Chromatogr B Analyt Technol Biomed Life Sci 776(1): 65-70.

Marin, G.H., J. Tentoni, and G. Cicchetti, [Megaloblastic anemia: rapid and economical study]. Sangre (Barc), 1997. 42(3): 235-8.

Biotin

Until recently, biotin deficiency was very difficult to determine in humans because this vitamin deficiency affects health in ways
that mimic many other conditions. Doctors were likely to overlook biotin deficiency until this test was discovered. Beta(ß)-
Hydroxyisovalerate is a specific and sensitive metabolic marker for functional biotin deficiency. As your biotin intake decreases,
your ß-Hydroxyisovalerate excretion increases.

Mock, D.M., Henrich, C.L., et al., Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid
excretion and a leucine challenge. Am J Clin Nutr, 2002. 76(5): 1061-8.

Lipoic Acid

Alpha-Lipoic acid (Lipoic Acid) is classified as a “vitamin-like” compound. It is sulfur containing and is involved in energy
metabolism, antioxidant protection, and insulin function. It protects cell membranes by interacting with vitamin C and
glutathione. Lipoic acid has been studied as an adjunct therapy for diabetes and liver disease. The urinary markers, Pyruvate
and Lactate, when elevated can indicate a need for supplemental lipoic acid.

5.
 Minerals (Elements)
Minerals make up about 4 to 5 percent of body weight, and not just in the skeleton! We need minerals for nerve
transmission, digestion, antibody production, metabolism of nutrients, and more. The term “Elemental Analysis” is
sometimes used because it is the chemical elements like magnesium, iron, and potassium that actually make up mineral
compounds. Just about all of the chemical elements that are found in soil or seawater are present in your body. The ones
found in very small amounts are called “trace elements”.

Measuring mineral concentrations inside your erythrocytes (red blood cells) is one of the best ways to determine their
adequacy. Minerals are important catalysts that spark many of the chemical reactions in your body.

Calcium and Magnesium

The most abundant mineral element in your body is Calcium, because it is the major element in bone. Serum and red blood
cell calcium, however, do not represent bone mineral content or dietary adequacy. The most extensively required element
is magnesium. Erythrocyte magnesium is a measure of magnesium adequacy. Magnesium is required for conversion of the
metabolic markers Orotate and Succinate. Some types of heart problems are aided by using the orotate form of magnesium.
Because the supply and regulation of calcium and magnesium are generally linked, it is usually best to use both calcium and
magnesium. Your age and sex can help to determine the best amount for supplementation. Normally, because of their role in
maintaining and repairing the body, calcium and magnesium must be consumed in hundreds of milligrams per day to maintain
a positive balance.

Chromium and Vanadium

The chromium and vanadium content of your erythrocytes can be accurately measured, although their levels are normally very
low. The major function of Chromium and Vanadium is to help insulin act on your cells to regulate blood sugar. We also assess
the metabolic marker of blood sugar utilization, ß-Hydroxybutyrate.

Copper

Copper is a part of enzymes, which are proteins that help biochemical reactions occur in every cell. Copper is involved in
the absorption, storage and metabolism of iron. The symptoms of a copper deficiency are similar to iron deficiency anemia.
(The liver makes a special protein, ceruloplasm, to transport copper and help convert iron to a form that can be used by other
tissues). Copper is utilized by most cells as a component of enzymes involved in energy production, protection of cells from free
radical damage, strengthening connective tissue, and brain neurotransmitter function. Excess zinc intake can result in a copper
deficiency when intake of copper is insufficient.

Manganese

Metabolic pathways used for energy production require

manganese and iron. Manganese is a component of several
enzymes involved in skin, bone and cartilage formation
and blood glucose control. Along with iron and copper, it
helps activate an important antioxidant enzyme, superoxide
dismutase.

Molybdenum

The trace element molybdenum activates enzymes

for building connective tissue and for toxin removal.
Molybdenum functions as a cofactor for metabolism of
sulfur-containing amino acids. Molybdenum should be
balanced with chromium and vanadium.

6.
Potassium

Erythrocyte potassium levels uniquely reveal your total body potassium status. Potassium is also an abundant mineral that
helps keep normal water balance between the cells and body fluids. Muscle contractions, nerve impulses and blood pressure rely
on availability of potassium. Excessive potassium levels in blood interfere with normal heart and nervous function and could
be caused by tissue damage. Low red blood cell potassium is rare and can result from poor dietary intake, diarrhea, disease or
certain medications.

Selenium

Erythrocytes are heavily loaded with protective selenium enzymes. Measuring erythrocyte selenium content is the best way to
check selenium status. Selenium is required for the production of glutathione, an important antioxidant. High Pyroglutamate
or low Sulfate levels in your urine indicate decreased levels of glutathione, which reveals a functional need for selenium.
Functioning synergistically with Vitamin E, selenium protects against cellular damage from oxygen radicals. Thyroid hormone
activation relies on the presence of sufficient selenium.

Zinc

Approximately 100 enzymes that support biochemical reactions in the body rely on zinc. Zinc is needed for wound healing, a
healthy immune system, a healthy sense of taste and smell, and for sexual maturation and development in children. The fatty
acid LA/DGLA and ALA/EPA ratios are markers that indicate functional zinc deficiency. Zinc also provides protection against
the toxic metal Cadmium.

Sudhakar, K., et al., Serum and erythrocyte magnesium levels in hypertensives and their first degree relatives. J Indian Med Assoc, 1999.
97(6): 211-3.

Paraskevopoulos, A., et al., Changes in erythrocyte calcium and potassium in patients during HD and CAPD. Int J Artif Organs, 2000.
23(11): 750-3.

Yegin, A., et al., Erythrocyte selenium-glutathione peroxidase activity is lower in patients with coronary atherosclerosis. Jpn Heart J, 1997.
38(6): 793-8.

Neggers, Y.H., et al., Plasma and erythrocyte zinc concentrations and their relationship to dietary zinc intake and zinc supplementation
during pregnancy in low-income African-American women. J Am Diet Assoc, 1997. 97(11): 1269-74.

Amino Acids
When dietary protein is digested and absorbed, amino acids flow into the blood stream. Amino acids have many important
functions in the body including the regulation of muscle and hormone activity and the formation and maintenance of every
tissue in your body (i.e., bone, ligaments, tendons, muscle). Conditions like chronic stress, depression, and toxic chemical
exposure increase your need for essential amino acids. Essential amino acids are those that must be provided by the diet because
the body cannot make them.

Essential Amino Acids

Supplementing essential amino acids can greatly benefit people who have low protein diets, have trouble adequately digesting
protein or who have increased demand for specific amino acids to maintain body processes. Between meals, amino acids supply
energy to keep cells functioning. There are certain situations where specific amino acids are recommended to supplement based
on particular metabolic needs.

For most people, the safest and most effective way of supporting your diet with amino acids is to take a balanced formula based
upon your amino acid profile. The table that follows your vitamin and mineral recommendations describes a formula that
can help meet your special needs. This table is based on your levels of essential amino acids in blood plasma. The following
essential and conditionally essential amino acids are measured: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine,
Phenylalanine, Threonine, Tryptophan, and Valine. The additional 10 amino acids that are measured, can be produced in
your body if the essential amino acids are adequately supplied.

7.
 The energy pathways in your cells require the key compounds Citrate, α-Ketoglutarate, and Succinate, which are formed from
essential amino acids. Low levels of Citrate, α-Ketoglutarate, and Succinate may indicate amino acid imbalances that can affect
your energy pathways. (see Figure 1). Another marker for potential amino acid supplementation is 5-Hydroxyindoleacetate
(5-HIA), the by-product of serotonin metabolism. The essential amino acid Tryptophan builds serotonin.

Teplan, V., Schuck, O., et al., Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving
a low-protein diet and recombinant human erythropoietin--a randomized controlled trial. Wien Klin Wochenschr, 2001 113(17-18): 661-9.

Arginine

Arginine is a conditionally essential amino acid that is critical for your cardiovascular health and detoxification functions.
The amino acid arginine is used to make the powerful blood vessel regulator nitric oxide. Nitric oxide acts to lower blood
pressure. Too little arginine can lead to high blood pressure. Too much arginine can lead to increased aging from oxidative
damage. Arginine is measured in blood, and markers of arginine insufficiency are measured in urine. High Citrate, Isocitrate,
Cis-aconitate, or Orotate can indicate arginine insufficiency. The essential amino acid Lysine needs to be present in amounts
balanced with arginine to ensure healthy immune system function.

Sass, J.O. and D. Skladal, Plasma concentrations and renal clearance of orotic acid in argininosuccinic acid synthetase deficiency. Pediatr
Nephrol, 1999. 13(9): 912-6.

Carnitine

Although not an essential amino acid, carnitine helps your body use fatty acids for energy. The body makes small amounts
of carnitine, but if it is not enough, fatty acids are not processed normally. Urinary excretion of the by-products Adipate and
Suberate increases (see Figure 1). Ethylmalonate, which comes from a different carnitine-dependent pathway, would also
accumulate with carnitine insufficiency.

Bohles, H., Z. Akcetin, et al. (1988). “The influence of i.v. MCT and carnitine on the excretion of dicarboxylic acids.” Beitr Infusionther Klin
Ernahr 20: 69-74.

5 – Hydroxytryptophan

Tryptophan is an essential amino acid required for the production of the neurotransmitter serotonin. 5-Hydroxytryptophan
(5-HTP) is an intermediate amino acid derivative in this synthetic process. Acting as a neurotransmitter, serotonin controls
functions relating to mood, behavior, appetite, and sleep. The compound 5–Hydroxyindoleacetate (5–HIA) is measured in
urine as a marker of serotonin metabolism. When this compound is elevated it indicates higher than normal turnover of
serotonin with potential depletion of tryptophan as a result. 5-HTP can be used as a dietary supplement to increase production
of serotonin as therapy for individuals who are depressed, have sleep problems, or chronic pain such as fibromyalgia. Serotonin
re-uptake inhibitors (Prozac, Zoloft etc.) often lead to elevated 5–HIA.

Birdsall, T.C., 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev, 1998. 3(4): 271-80.

Glycine

Glycine is an amino acid serving several important purposes within the body, including detoxification, DNA formation, the
synthesis of hemoglobin, and as a part of brain neurotransmission pathways. Glycine and serine are interchangeable. Low
plasma levels of Glycine and Serine can serve as markers for long term repletion of essential amino acids. In the liver, glycine
helps to convert many potentially harmful substances, including toxic materials such as benzoic acid (benzoate) into harmless
forms. If urinary Benzoate levels are elevated, it suggests you may benefit from extra glycine. A second detoxification role of
glycine is to serve as a necessary part of glutathione, a compound needed by the liver. Urinary Pyroglutamate levels reflect loss
of glutathione available to the body that improves when extra glycine is provided.

Temellini, A., Megarero, S., et al., Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual
variability. Xenobiotica, 1993. 23(12): 1427-33.

Persaud, C., T. Forrester, et al. (1996). Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased during recovery from severe
childhood malnutrition and responds to supplemental glycine. J Nutr 126(11): 2823-30.

8.
N-Acetyl Cysteine

Glutathione is constantly used up in the

removal of toxic molecules and prevention of
oxidative damage. Elevated levels of the marker
Pyroglutamate reveal that glutathione is being
lost at a high rate. Sulfate excretion is another
way to check your total body sulfur-containing
amino acid status. Low urinary Sulfate is an
indication that total body glutathione is low and
sulfur-containing amino acids are needed. The
amino acid N-Acetylcysteine is one agent for
effectively raising your glutathione and sulfate
levels.

Kim, H. J., J. H. Cho, et al. (1995). Depletion of

hepatic 3’-phosphoadenosine 5’-phosphosulfate
(PAPS) and sulfate in rats by xenobiotics that
are sulfated. J Pharmacol Exp Ther 275(2): 654-8.

Lykkesfeldt, J., T. M. Hagen, et al. (1998). Age-

associated decline in ascorbic acid concentration,
recycling, and biosynthesis in rat hepatocytes-
reversal with (R)-alpha-lipoic acid
supplementation. Faseb J 12(12): 1183-9.

Fatty Acids
Fat is necessary for every cell membrane, for nerve coverings, for hormone production, for vitamin absorption, and more.
Most of us get a lot of fat in our diet, but it usually is not the quality fat we should be getting. We need to eat more “good” fats
from fish, flax seed, olive, vegetable, and nut oils (omega 3, 6, and 9 fats respectively) and less saturated oils and trans fats (or
hydrogenated oils) contained in processed foods. Elevations in Palmitelaidic and/or Total C:18 Trans indicate excessive intake
of foods containing trans fats. Palmitic and Stearic acids are significant markers for high consumption of saturated fats. The
families of healthy fats called omega-3, omega-6, and omega-9 protect against heart disease and help skin and joints stay young
and supple. Hydrogenated and partially hydrogenated oils often contained in shortening, margarine, and many baked goods,
as well as excessive dietary saturated fats from animal products, can cause health problems on a cellular level and increase heart
disease risk. The fatty acid profile shows the balance of fats and their metabolites in plasma. Your overall balance of omega-3 and
omega-6 fats is represented by the ratios of AA/EPA (arachidonic acid/eicosapentaenoic acid) and EPA/DGLA (Eicosapentaenoic
acid/Dihomogammalinolenic acid). Overall need for polyunsaturated fatty acids is represented by Mead acid and the Triene/
Tetraene ratio. This ratio is calculated by dividing Mead acid by arachidonic acid values. The Saturated/Unsaturated ratio
shows the overall balance of these classes of fatty acids. It can help give a more complete picture of essential fatty acid status.
How healthy is the fat you’re giving your body?

Fish Oil and Flaxseed Oil (Polyunsaturated Omega-3 Fatty Acids)

This family begins with Alpha linolenic acid (ALA). ALA is an “essential” fatty acid (EFA), meaning that your body cannot
make it and you must obtain it from your diet. ALA may be converted into Eicosapentaenoic acid (EPA), a longer fatty acid
that is involved in regulation of inflammatory processes and prevention of platelet “stickiness.” Diminished platelet aggregation
reduces the blood clotting that can lead to heart attack or stroke. Your body can make the other polyunsaturated omega-3 fatty
acids from ALA. However, many things can interfere with this process including zinc deficiency, alcohol, obesity, and aging.
Docosapentaenoic acid (DHA) is another omega-3 fatty acid and that is integral to brain development in fetuses and infants.
The best-known sources of omega-3 fatty acids are cold-water fish, flaxseed, soybean, walnuts and their oils.

Thies, F., et al., Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids,
decreases natural killer cell activity in healthy subjects aged >55 y. Am J Clin Nutr, 2001. 73(3): 539-48.

9.
 Black Currant Seed Oil (Polyunsaturated Omega-6 Fatty Acids)

Linoleic acid (LA) is another “essential” fatty acid (EFA). It is used to make the major membrane polyunsaturated fatty acid
Arachidonic acid (AA). High LA relative to other essential fatty acids leads to products that favor inflammatory processes and
excessive amounts can lead to cardiovascular disease. Your body can make other omega-6 fatty acids from LA, like Gamma
linoleic acid (GLA), but this process can be blocked by nutrient deficiencies, alcohol abuse, obesity, and aging similarly to
omega-3 production pathways mentioned above. One of the best overall markers of EFA insufficiencies is the ratio of Mead to
Archidonic acids called the Triene/Tetraene ratio.

Suresh, Y. and U.N. Das, Protective action of arachidonic acid against alloxan-induced cytotoxicity and diabetes mellitus. Prostaglandins
Leukot Essent Fatty Acids, 2001. 64(1): 37-52.

Olive Oil (Monounsaturated Fatty Acids)

These fatty acids are found in foods such as nuts, olives, and their oils. You may eat Oleic acid by using olive oil or your body
will produce it from saturated fatty acids. Either way, you need this type of fat to build cell membranes that function properly.
The several other monounsaturated fatty acids measured are usually minor components. They may reveal metabolic imbalances
that affect nerve function and cellular energy production.

Ferrara, L.A., et al., Olive oil and reduced need for antihypertensive medications. Arch Intern Med, 2000. 160(6): 837-42.

Environmental Toxin Exposure Markers

One of the most common organic compounds in our environment is xylene. Produced from coal tar or crude oil, xylene is used
as a solvent for paints and paint thinners, and its vapors are released from many building and decorating materials such as
varnishes and new carpets. Excretion of 2-Methylhippurate is a sensitive and specific marker for xylene exposure. Glucarate, on
the other hand, serves as a biomarker for your exposure to a wide array of potentially toxic chemicals. High urinary Glucarate
suggests above normal exposure to pesticides, herbicides, fungicides, petrochemicals, alcohol, pharmaceutical compounds, or
toxins produced in the gastrointestinal tract.

Heavy metals that can be toxic to the body include Aluminum, Cadmium, Lead, and Mercury. As mentioned earlier, the
minerals Zinc and Selenium offer protection against cadmium and mercury respectively. Your healthcare provider may discuss
options with you for heavy metal removal if deemed necessary.

Ferreira, M., Jr., Buchet, J. P., et al., Determinants of urinary thioethers, D-glucaric acid and mutagenicity after exposure to polycyclic aromatic
hydrocarbons assessed by air monitoring and measurement of 1-hydroxypyrene in urine: a cross-sectional study in workers of coke and
graphite-electrode-producing plants. Int Arch Occup Environ Health, 1994. 65(5): 329-38.

Intestinal Microbial Balance Markers

The compounds listed below normally appear in urine only at low levels. With the exception of Hippurate, the compounds
are not normally produced in the cells of your body. However, unfriendly intestinal microorganisms can manufacture them in
relatively high quantities. The compounds are then absorbed into the blood from the intestines and eventually appear in the
urine. Microbial overgrowth can lead to a wide variety of symptoms due to reactions to the toxic products produced by bacteria,
parasites, or fungi. Various patterns of the compounds reported appear elevated in conditions of general intestinal microbial
overgrowth.

Probiotics and Antibiotics

In health, the intestinal tract contains large amounts of beneficial bacteria that produce some B vitamins and provide stimulus
for proper immune function. However, if your stomach acid is not adequate, if you fail to digest protein, or if your diet does
not supply sufficient fiber, the resulting overgrowth of unfavorable bacteria can release toxic products that your body must
remove. These toxic products include: Benzoate, Hippurate, Phenylacetate, Phenylproprionate, p-Hydroxybenzoate, p-
Hydroxyphenylacetate, Indican, and Tricarballylate. Your potential to benefit from consuming extra sources of favorable
organisms (called probiotics) may go up as the number of toxic compounds and their concentrations increase.

10.
 Valkova, N., F. Lepine, et al. (2001). Hydrolysis of 4-hydroxybenzoic acid
esters (parabens) and their aerobic transformation into phenol by the resistant
Enterobacter cloacae strain EM. Appl Environ Microbiol 67(6): 2404-9.

Tohyama, K., Y. Kobayashi, et al. (1981). Effect of lactobacilli on urinary indican

excretion in gnotobiotic rats and in man. Microbiol Immunol 25(2): 101-12.

Lactobacillus Acidophilus
D-Lactate elevation is an exception to the use of probiotics just described.
Lactobacillus acidophilus is widely considered a favorable bacterium to
colonize the human gut. It has beneficial effects in many individuals.
However, if you have any tendency for carbohydrate malabsorption, even
favorable organisms (e.g., L. acidophilus) can grow so fast that your blood
becomes highly acidic due to the formation of D-Lactate. This condition is
revealed by high D-Lactate in urine. Discontinuing all probiotic intervention
while considering antibiotic therapy may be warranted when D-Lactate is
high.

Vella, A. and G. Farrugia, D-lactic acidosis: pathologic consequence of saprophytism.

Mayo Clin Proc, 1998. 73(5): 451-6.

Godey, F., A. Bouasria, et al. (2000). Don’t forget to test for D-lactic acid in short
bowel syndrome. Am J Gastroenterol 95(12): 3675-7.

Saccharomyces boulardii
It is difficult to know the exact identification of organisms that may be producing the compounds found in your urine.
However, one specific compound, Dihydroxyphenylpropionate seems to be strongly associated with a particularly troublesome
type of bacteria called Clostridia. This organism is frequently the cause of travelers diarrhea, but its by-products may
produce other symptoms. Species of Clostridia are particularly susceptible to displacement by the favorable organism called
Saccharomyces boulardii that is available in capsules.

Schwarz, G., R. Bauder, et al. (1989). Microbial metabolism of quinoline and related compounds. II. Degradation of quinoline by
Pseudomonas fluorescens 3, Pseudomonas putida 86 and Rhodococcus spec. B1. Biol Chem Hoppe Seyler 370(11): 1183-9.

Anti-fungals
Yeast is another class of microbes that can chronically grow in the intestinal tract and cause health effects through the release
of toxic metabolites. Because of the multiple, non-specific symptoms that they can produce, doctors have searched for ways to
know when yeast overgrowth is a problem. Tartarate, Citramalate, and Arabinitol are uniquely produced by intestinal yeast,
and the degree of elevation is a useful marker of their growth. Favorable organisms and herbal or pharmaceutical antifungal
agents suppress intestinal yeast.

Christensson B. Sigmundsdottir G, and Larsson L, D-arabinitol-- a marker for invasive candidiasis. Med Mycol 1999; 37(6): 391-6.

Glossary

11.
 Glossary
Amino Acids-Essential
Arginine: Essential for the body’s processing of nitrogen,
arginine is found in all proteins and is vital for muscle
metabolism and liver function. It can inhibit tumor growth,
promote wound healing and lower cholesterol in experimental
animals. Low levels often reflect poor digestion of protein or
increased demands for detoxification.
Histidine: Histidine can indicate the status of protein
metabolism in the body, and during stress it is the most
essential amino acid. Low levels of histidine are often
associated with rheumatoid arthritis and poor dietary protein;
high levels may indicate excessive protein intake.
Isoleucine: Similar to leucine, isoleucine is handled through
carbohydrate and fat metabolism. Studies have shown that
low levels of isoleucine in plasma indicate an increased need
for niacin. Chronic deficiency can cause hypoglycemia, loss of
muscle mass, or inability to build muscle.
Leucine: Abundant in muscle tissue, leucine stimulates
insulin production and promotes protein synthesis, like
valine. Leucine cannot substitute for glucose in the fasting
state, but it is converted into other compounds called “ketone
bodies” that serve as an alternate source of energy for the
body.
Lysine: Found in great quantities in muscle tissues, Iysine is
well known for its use in treating and even preventing herpes
infections. Prolonged stress results in low levels of this amino
acid. Lysine can help fight lead toxicity and can help treat
osteoporosis by reducing calcium loss.
Methionine: Methionine is extremely important in the
body’s synthesis of many vital compounds. It helps neutralize
toxins, donates sulfur when dietary supply is inadequate, and
is instrumental against depression. Low levels may indicate a
poor-quality protein diet.
Phenylalanine: A precursor for the catecholamine
neurotransmitters, the chemicals that communicate between
nerve cells, phenylalanine can relieve pain, alleviate
depression, and suppress the appetite. Low levels may indicate
a stressful lifestyle, leading to memory loss, fatigue, and
depression.
Threonine: Threonine is an immune system stimulant
that can promote the growth of the thymus gland, help
with depression, and improve spasticity in legs. It is used in
multiple sclerosis treatment.
Tryptophan: Tryptophan has special functions in brain
chemistry and is the precursor to the brain chemical serotonin
and the vitamin niacin in the body. Low levels of tryptophan
are correlated with the degree of depression in patients.
Tryptophan has been shown to help induce sleep in those
12.
with insomnia. Foods high in tryptophan include turkey,
bananas, low fat milk, lentils, and eggs.
Valine: Found in high concentrations in muscle tissue,
valine is vital for protein synthesis. Low levels may indicate a
potential muscle loss; high levels may indicate B6 deficiency.
Taurine: An antioxidant, taurine is a neurotransmitter
with anticonvulsant properties. It can improve symptoms of
depression, stimulate insulin release, and enhance cholesterol
excretion. Taurine is used to treat heart disease, hypertension,
and epilepsy.
Amino Acids-Non-Essential
Asparagine: Found in asparagus, asparagine is closely related
to aspartic acid and is required for protein synthesis and for
peptide hormone production. Low levels may indicate a need
for magnesium.
Aspartic acid: A precursor of nucleic acids in DNA and RNA,
aspartic acid can be used as an energy source and aids in the
detoxification of ammonia. Aspartic acid supplementation
has been shown to increase stamina. High levels may
indicate an energy problem that would respond to B-vitamin
supplementation.
Citrulline: High levels of citrulline may indicate the
potential for the build-up of toxic ammonia in the system. A
low protein diet and/or supplementation of magnesium and
aspartic acid can help control ammonia.
Glutamic acid: Glutamic acid functions as an excitatory
neurotransmitter in the central nervous system and is
important in removing ammonia from the brain. Low
glutamic acid levels and high glutamine levels often indicate
mild hyperammonemia conditions, with symptoms including
headache, irritability, and fatigue.
Glutamine: Glutamine is the most abundant amino acid
in the blood and is an important source of energy for many
tissues in the body. It is derived from the amino acids histidine
and glutamic acid. Low levels may reflect insufficient essential
amino acid dietary intake. See Glutamic acid.
Glycine: Glycine is used in the body as an energy source,
to detoxify, and for brain function. High levels may indicate
deficits in brain chemistry associated with behavioral or
emotional disturbances. Glycine is used in the synthesis
of hemoglobin, creatine, DNA and RNA and is involved in
maintaining blood sugar levels. Low levels may produce
hypoglycemic-like symptoms.
Homocysteine: The normal route by which methionine
is broken down leads to the intermediate formation of
homocysteine. Enzymes in this pathway require vitamin B12,
folic acid, and vitamin B6 to allow this pathway to function
normally. If the vitamins are inadequate, the enzyme step
falls behind and homocysteine builds up. High homocysteine
indicates deficiencies of these vitamins, and is a risk factor for
heart disease independent of high cholesterol risk.
Ornithine: Ornithine can stimulate the release of growth
hormone and is important for building body tissues.
Ornithine elevation may indicate a higher body burden of
ammonia. Alpha-ketoglutaric acid and vitamin B6 are useful in
clearing chronic minor excesses of ammonia.
Serine: Serine can be used as an energy source. Formed from
threonine and phosphoserine (requiring B6, manganese,
and magnesium), serine is necessary for the biosynthesis
of acetylcholine, a neurotransmitter used in memory
function. Low serine may lead to problems with methionine
metabolism.
Tyrosine: Tyrosine serves as a precursor for thyroid hormone,
the catecholamine neurotransmitters, and melanin. Low
levels of tyrosine have been associated with hypothyroidism,
depression and blood pressure disorders. High levels may
indicate an inability to utilize tyrosine properly, perhaps
because of low levels of iron, copper, iodine, B6, and vitamin C.
Antioxidant Protection
8-Hydroxy-2’-deoxyguanosine: See under Organic
Acids
of vitamin E. It plays a large role in the defense against age-
producing oxygen free radical attacks. Vitamin E protects
polyunsaturated fatty acids, proteins and DNA from damage.
Fatty Acids
Alpha linolenic acid: Abbreviated as ALA or LNA; this is
one of the least abundant of the essential fatty acids in most
diets. It is found in flax, hemp, rape (canola) seed, soybean,
walnut, and dark-green leaves. The wide range of symptoms
associated with ALA deficiency is due to the function of this
fatty acid in critical cell processes such as maintaining cell
membranes.
Arachidic acid: This saturated fatty acid can be utilized
as an energy source, but it serves no other known special
function. High levels can interfere with the reactions needed
to produce DGLA, EPA and AA, important metabolites of
common dietary fatty acids.
Arachidonic acid (AA): AA is converted into various
compounds for local control of many tissue responses; several
of these compounds have potent pro-inflammatory and blood
clotting activity. Because of the prevalence of corn and corn
oil products in feed for cattle and hogs, diets high in these
meats are rich in AA. High AA promotes gall stone formation
by stimulating mucin production.

ß-Carotene: Carotenoids serve as antioxidants in the

body. As their name implies, carrots are rich sources of these
nutrients. ß-Carotene can be changed to vitamin A and thus
serves two roles. The total additional antioxidant protection
that it affords is very significant.

Coenzyme Q10: The main reason that coenzyme Q10

(CoQ10) is an effective antioxidant is that it helps reduce the
formation of damaging oxygen radicals in the cells of your
body. Control of the final phase of the oxidation pathway
for food components is dependent on CoQ10. Individuals
frequently need extra CoQ10 for proper energy production,
especially when conditions of heart disease or muscle
cramping are present.

Lipid Peroxides: This test actually measures the rate at

which oxidative damage is currently proceeding in your
tissues. Some level of ongoing damage is inevitable and is
reversed by the production of fresh new cells and tissues. If
your level of lipid peroxides is high, you may need to increase
the various nutrients that afford antioxidant protection.
Factors that lead to higher lipid peroxidation are smoking,
chronic inflammatory disease, and high polyunsaturated fat
intake with inadequate vitamin E.

Vitamin A: This vitamin has many essential functions

involving vision, reproduction and skin health in addition to
its antioxidant role. It is one of the fat soluble nutrients that
helps protect cell membranes from the destructive effects of
oxygen products.

Vitamin E: Antioxidant protection is the primary function

13.
 also requires the action of an enzyme that may be low due to
inadequate zinc, magnesium, or vitamins B3, B6, and C. High
levels of saturated, monounsaturated, trans-fatty acids, and
cholesterol also slow the conversion of ALA to EPA.

Erucic acid: This fatty acid is found in rape/mustard

seed (canola) oil. It is helpful in individuals with
adrenoleukodystrophy.

Gamma linolenic acid (GLA): This fatty acid is found in

hemp, borage, black currant, and evening primrose oils. It can
be produced in human tissues by the action of enzymes on
linoleic acid. Because of interferences with this production,
however, many people are deficient in this important fatty
acid. GLA is used to create DGLA (above).

Linoleic acid (LA): Linoleic acid is the starting point for

the production of local hormones known as prostanoids,
including the prostaglandins, and it serves a role in the
structural integrity of the cells. It is the most abundant
polyunsaturated fatty acid in most human tissues. Low levels
indicate dietary insufficiency which leads to a variety of
Behenic, lignoceric & hexacosanoic acids:
symptoms.
Accumulation of these fatty acids is associated with
degenerative diseases of the central nervous system and with
Mead acid: Chronic deficiency of essential fatty acids causes
adrenoleukodystrophy. They are very long chain saturated
the body to produce higher levels of Mead acid to help take
fatty acids that are used to build sphingolipids of nerve
the place of the normal products. Thus, elevated levels of
membranes. Several genetic disorders involve accumulation of
Mead acid indicate long-term essential fatty acid deficiency.
sphingolipids, usually due to a lack of the enzymes necessary
to maintain the turnover of membrane components.
Oleic acid: Oleic acid is present in all foods that contain fat
and is easily produced by the fatty acid synthetic pathways
Dihomogammalinolenic acid (DGLA): DGLA is critical
present in normal human liver cells. It helps govern the
for a large number of tissue controls. Low levels of DGLA
fluidity of cell membranes. A diet rich in oleic acid reduces
result from diets low in the essential fatty acid LA. Deficiency
foam cell accumulation rates on the arterial wall and thereby
leads to problems with blood vessels, blood pressure, immune
lowers the chances of atherosclerosis. Olive oil is a quality and
and reproductive functions. Supplementation with borage or
easily consumed source of oleic acid.
black currant oils should be considered.
Palmitic acid: High levels of palmitic acid lead to increased
Docosahexaenoic acid (DHA): The growth and
serum cholesterol levels and thus, to increased risk of
development of the central nervous system is dependent
atherosclerosis, cardiovascular disease, and stroke. Palmitic
upon an adequate amount of the highly unsaturated fatty
acid is high in palm kernel and coconut oils.
acids, docosapentaenoic (DPA) and docosahexaenoic acid
(DHA). Deficiencies can lead to ADD/ADHD and failures in
Penta-, Hepta-, and Nonadecanoic Acids (odd-chain
development of the visual system.
fatty acids): When the body is supplied with adequate
amounts of vitamins, the fatty acids that are produced by the
Docosatetraenoic acid (DTA): This fatty acid accumulates
tissues all contain even numbers of carbon atoms. Deficiency
in adipose tissue from which it is mobilized in the fasting
of vitamin B12 results in accumulation of the odd numbered
state. The level of DTA may have usefulness in monitoring the
long chain fatty acids.
metabolic aspects of weight control and especially in avoiding
the risk of essential fatty acid deficiencies while maintaining
Palmitelaidic and elaidic acids: The trans fatty acids,
a very low fat diet. When an obese person on a weight loss
elaidic and palmitelaidic, are prevalent in most diets because
program shows the level of DTA beginning to fall, they may
of the widespread use of hydrogenated oils in margarines,
be entering a state of essential fatty acid deprivation.
bakery products, and peanut butters. They behave like
saturated fats on the one hand, leading to higher cholesterol
Eicosapentaenoic acid (EPA): Insufficiencies of EPA are
levels. They mimic unsaturated fats on the other hand,
likely the most prevalent fatty acid abnormality in western
interfering with the normal production of necessary products.
societies. Arthritis, heart disease, and aging result from the
The net effect is to raise LDL (bad) cholesterol and lower
effects of unchecked inflammatory response. Although EPA
HDL (good) cholesterol. The consensus among experts is that
can be produced from the essential fatty acid ALA, dietary
hydrogenated oils should be avoided.
intake of this fatty acid is generally poor, and the conversion

14.
Stearic acid: Stearic acid is a saturated fatty acid that can
lead to higher cholesterol, so high levels in plasma are a risk
factor in atherosclerotic vascular disease. (See palmitic acid
above.)
Minerals (Elements)-Nutrient
Chromium: Found in liver, brewer’s yeast, black pepper, and
whole grains, chromium aids in lowering LDL cholesterol and
raising HDL cholesterol. Some studies have found lowered
chromium in subjects with adult diabetes. Sugar metabolism
was improved in over 80% of individuals who have a slight
glucose intolerance by using 200 mcg/d of a chromium
supplement.
Copper: Copper serves as a cofactor in lipid metabolism,
liver detoxification and neurological control. Extreme copper
deficiency can lead to anemia, neurological disorders, bone
disturbance, cardiovascular degeneration and accelerated
aging. High copper levels have been associated with elevated
systolic blood pressure and learning and other mental
disorders. Food sources include shellfish, nuts, miso, northern
and navy beans.
Magnesium: The magnesium content of red blood cells is a
good indicator of long-term magnesium status, and low levels
indicate nutritional deficiency. Because many of the enzymes
of energy transfer require magnesium, a deficiency affects
all tissues. Nervous tissue demonstrates deficiency with the
appearance of nausea, dullness, listlessness, loss of appetite,
and rapid hair loss. Magnesium is found in nuts, beans, and
dark green vegetables.
Manganese: Individuals demonstrate large variations in
manganese retention, indicating wide ranging requirements
for this trace element. Disorders known to be associated with
manganese deficiency include impaired growth, skeletal
abnormalities, disturbed or depressed reproductive function
and defects in lipid and carbohydrate metabolism.
Selenium: Selenium affords protection against the damaging
effects of oxygen. Because red blood cells transport oxygen,
the threat of oxidative damage to these cells is very great. They
survive their normal 120 days only because of the protective
effects of antioxidants, among which glutathione, and thus
selenium, is quantitatively the most important.
Zinc: Zinc is the activating factor in any tissue replacement
process. Low zinc levels have been associated with chronic
skin disorder, slow wound healing, poor growth, reproductive
dysfunction, and low immune response. Problems that may
arise from high zinc include iron non-responsive anemia
due to relative copper deficiency, increased vascular disease
risk due to lowered HDL levels, and reduced protection from
oxidant damage.
Minerals (Elements)-Toxic
Aluminum: Deodorants, toothpaste, and aluminum pots
and pans are all potential sources of increased exposure to
aluminum. The toxic effects of aluminum accumulation are
mainly associated with impaired bone growth and brain cell
development.
Cadmium: Airborne particles from engine exhaust or
tobacco smoke are one route of exposure to the toxic element
cadmium. The essential element zinc can protect against toxic
effects of cadmium, which include impaired kidney function
and hypertension.
Lead: Monitoring of blood lead levels in school children is
mandated by law in some counties and locales in the U.S.,
because of the high prevalence of toxic lead levels and the
associated learning impairment. In addition to central nervous
system effects, lead can impair function in bones, joints, and
muscles.
Mercury: Mercury is in the amalgam fillings for dental
cavities. Mercury also is used as a preservative (thimerosol)
for most vaccinations given to children. Additionally, it is
used by the ton in industries that process chemicals and
make batteries. Individuals vary in their tolerance for low-
level mercury exposure. Some organic forms of mercury are
extremely toxic.
Organic Acids
2-Methylhippurate: This compound is a metabolite of the
detoxification of the common solvent, xylene. Elevations
indicate an exposure to this potentially toxic compound
found in paint, paint thinners, and varnishes.
5-Hydroxyindolacetate (5-HIA): Breakdown of
the neurotransmitter serotonin leads to excretion of 5-
hydroxyindoleacetate. Inadequate production of serotonin
has been associated with constipation, depression, fatigue,
insomnia, suicide, attention deficit and behavioral disorders.
Dietary therapy should focus on protein digestion via stomach
acid and pancreatic enzymes and consumption of foods high
in tryptophan.
8-Hydroxy-2’-deoxyguanosine (8-OHdG): Urinary
levels of 8-OHdG are used as a non-invasive marker of DNA
damage or oxidative stress. Under normal conditions, DNA
damage always takes place, but is kept to a minimum by
the cell’s protective mechanisms that include a suite of
antioxidant species as well as efficient repair enzymes. Under
certain circumstances, the fine balance between pro-oxidant
species and protective mechanisms can be upset, resulting in a
condition termed “oxidative stress.” Although numerous DNA
damage products can be formed, the one most often studied
is 8-OHdG. When oxidative damage occurs to DNA, repair
mechanisms remove this product as the marker, 8-Hydroxy-
2’-deoxyguanosine (8-OHdG), which is excreted unchanged in
the urine.
15.

Adipate, Suberate, and Ethylmalonate: Adipate and
suberate are short chain dicarboxylic fatty acids. Low levels
of carnitine cause inadequate transfer of fatty acids into the
cell’s energy production processes, producing excess amounts
of adipate, suberate, and ethylmalonate. Supplementation of
carnitine and other supportive nutrients is indicated when
these substances are elevated.
α-Ketoisovalerate, α-Ketoisocaproate & α-Keto-ß-
methylvalerate: These compounds are derived from the
branched chain amino acids, isoleucine, leucine and valine,
respectively. The B-complex vitamin cofactors, B1, B2, B3, B5
and lipoic acid, are required to metabolize these keto acids.
Elevations of these indicate the insufficiency of these vitamins,
especially thiamin.
ß-Hydroxybutyrate: This compound is elevated in
conditions where blood sugar cannot supply energy or where
utilization or mobilization of carbohydrate stores is inefficient.
Chromium and vanadium supplementation may support
carbohydrate utilization by improving the action of insulin.
ß-Hydroxyisovalerate: This compound is elevated in
biotin deficiency. Biotin deficiencies develop in a substantial
minority of normal pregnancies and in people on long-term
anticonvulsant therapy. Symptoms can include hair loss, skin
rash, dermatitis, immune deficiencies and muscle weakness.
Citrate, Isocitrate, α-ketoglutarate, cis-Aconitate,
Succinate, and Fumarate: These components are citric acid
cycle (CAC) intermediates in the body’s metabolic pathway
that generate cellular energy. The Krebs or CAC is the source
of basic structural or anabolic molecules that feed and support
organ maintenance and neurological cofactors and minerals
16.
for their function. Higher levels of CAC intermediates in urine
indicate inefficiencies in energy production in the cells.
Creatinine: This compound is excreted in urine at a
relatively constant rate, depending on total lean muscle mass.
It is measured in order to better standardize the amounts
of other compounds measured in urine. You will see the
concentration unit of mcg/mg creatinine indicating that the
total amount of compound found has been divided by the
creatinine concentration.
D-Lactate: Under conditions of carbohydrate malabsorption
or sudden suppression of other bacteria in the small intestine,
D-lactate can be produced in large quantities by Lactobacillus
acidophoillus and a few other organisms. The compound
reported as simply “Lactate” is largely the L-lactate form that
is produced by metabolic activity in muscle and other tissues,
not by L. acidophilus.
Hydroxymethylglutarate (HMG): HMG is the metabolic
precursor of cholesterol and coenzyme Q10 (CoQ1O). Low
levels may reflect inadequate synthesis and possible deficiency
of CoQ1O. CoQ1O is required for cellular energy production,
is a vital cofactor in active tissue like heart muscle, and is a
potent antioxidant.
Indican: Indican is a by-product from breakdown of dietary
protein in the upper bowel. Bacteria are responsible for the
production of indican. Indican is present only at low levels
in a healthy person. An elevated level of urinary indican is an
indication of upper bowel bacterial overgrowth or dysbiosis.
Indican excretion is reduced when the intestines are populated
with strains of lactobacillus.
Kynurenate: Early in the same pathway described under
xanthurenate, this compound may be formed through
oxidation of kynurenin. In the brain, this pathway helps to
control the sensitivity of neuronal responses. Kynurenate
elevations tend to accompany quinolinate as a kind of
balancing of the strong effects of that compound. Vitamin B6
can help support metabolism of kynurenate.
Lactate & Pyruvate: The metabolism of these two
compounds requires cofactors derived from thiamin,
riboflavin, niacin, lipoic acid, and pantothenic acid. Elevated
levels of pyruvate may reflect metabolic failure due to a need
for increased B vitamins, particularly thiamin and pantothenic
acid. Lactate accumulates when coenzyme Q10 is insufficient.
Decreased lactate is seen in people with very little physical
activity or in highly trained athletes, who have such efficient
conversion of lactate to glucose that they also demonstrate
lower lactate levels.
Methylmalonate: The metabolism of this compound
requires a vitamin B12-dependent enzyme; the lack of vitamin
B12 impairs this conversion, leading to accumulation of
methylmalonate. High levels indicate a functional deficiency
of vitamin B12.
Orotate: Orotic acid accumulation is a sensitive marker
of ammonia build-up and consequently of arginine
availability. Most of the symptoms of arginine deprivation
can be accounted for by decreased efficiency of ammonia
detoxification. Supplementing alpha-ketoglutarate,
magnesium, aspartic and glutamic acids can help.
p-Hydroxybenzoate, p-Hydroxyphenylacetate
and Tricarballylate: These compounds are produced by
microbial action on tyrosine and phenylalanine and are
markers of bacterial growth in the gut. Small amounts are
present normally. Use of antibiotics can encourage the growth
of bacteria that produce greater amounts of these compounds.
p-Hydroxyphenylactate (HPLA): HPLA is a carcinogenic
metabolite of tyrosine that increases lipid peroxidation in the
liver. HPLA is an important regulator of normal and malignant
cell growth and it appears to mediate the cancer-promoting
effects of estrogen. High doses of vitamin C have been shown
to inhibit the excretion of HPLA in people with some forms of
cancer.
Vanilmandelate (VMA) & Homovanillate (HVA):
These two compounds are metabolites of epinephrine and
norepinephrine. Low urinary levels have been associated with
low central nervous system levels of these neurotransmitters.
Symptoms associated with this condition are depression,
sleep disturbances, inability to deal with stress, and fatigue.
Treatments to improve digestion and supplementation of
amino acid precursors can help.
Xanthurenate: Xanthurenate is produced as a by-product
of the pathway that converts L-tryptophan into niacin. When
vitamin B6 (or pyridoxal-5-phosphate) is abundant, very little
xanthurenate is formed. Insufficiency of B6, however, causes
much higher excretion of xanthurenate.

Pyroglutamate: Pyroglutamate is a form of the amino acid

glutamic acid. Small amounts are always present, but higher
amounts mean the kidney is conserving amino acids at the
expense of glutathione, which is important for protection of
every cell from oxidation. Glutamic acid, α-KG, methionine,
and glycine can help rebuild total body glutathione.

Quinolinate: The NMDA receptors that are activated by

glutamate to increase our awareness of pain and other body
signals are highly sensitive to the toxic effects of quinolinate.
With chronic production of quinolinate by macrophages
in the brain, the NMDA receptor-containing neurons can
degenerate and be lost. Many (if not all) inflammatory brain
degenerative conditions are accompanied by elevation of
quinolinate produced by macrophages. Urinary quinolinate
can also be formed in the liver where the kynurenin pathway
is used to clear excess L-tryptophan and to form nicotinate
(vitamin B3).

Sulfate: Sulfation pathways are important for the body’s

transformation of many drugs, steroid hormones, and toxic
compounds. The ratio of sulfate to creatinine is used to assess
the body’s reserve of sulfur-containing compounds (especially
glutathione) for these detoxifications. When the ratio of
sulfate to creatinine is low, these stores need replenishment.
Cysteine, taurine, and salts of sulfate are used to replenish
sulfur pathways and restore the liver’s supply of sulfate.

Tartarate & Citramalate: These compounds are called

anti-metabolites and they impact pathways of central
energy production. They have been found to be elevated in
children who began to display autistic traits after repeated
treatment with broad spectrum antibiotics. Elevations of
these compounds suggest treatment with bowel detoxification
regimens to normalize the microbial flora of the gut.

17.
Figure 1. Central Energy Pathways

Digestion FATS CARBOHYDRATES PROTEINS

and
STAGE I

Assimilation

Fatty Acids, Gycerol Glucose & Other Sugars Amino Acids

Cholesterol
Keto Acids
Adipate Carnitine Pyruvate Lactate
B1, B2, B3, B5, Lipoate
Suberate B1, B2, B3, B5, Lipoate
Ethylmalonate
Intermediary Acetyl CoA
Metabolism ß-Hydroxybutyrate

Asp Oxaloacetate Citrate

Citric Acid Cycle
B3 cis-Aconitate
STAGE II

Malate Cysteine, Fe ++ Glu

His
Isocitrate Arg
Tyr Pro
Fumarate B3, Mg, Mn Gln
Phe
B2 α-Ketoglutarate
Succinate B1, B2, B3, B5, Lipoate
Mg Succinyl-CoA
Ile
Val
Electron Transport NADH Met
and
Oxidative
STAGE III

NADH
Phosphorylation Dehydrogenase

Coenzyme Q10 ADP + Pi

Cytochromes
Hydroxymethylglutarate ATP Energy for muscle and
nerve function and for
O2 H2O building new tissue
Note: Vitamin & mineral requirements for
cofactors are shown in light blue box. Compounds Reported in IONTM Profile are Printed in Red
Elevations of metabolites before these steps
indicate functional deficit of the nutrients.