Wednesday, May 21, 2008

NUTRITIONAL PROFILE: Glutathione Depletion and Blocked Methylation Cycle (Post 10)

Remember that this is juat a post of my blog, and it evolves, so to see the full story go to: (English) or (Spanish)
My current doc: Josepa Rigau Av Catalunya, 12, 3º, 1ª 43002 Tarragona Spain +34977220358 (I do recommend! hoeopathy and biological medicine, significant improvement)
My previous docs: De Meirleir (, Dra Quintana (CMD), (Lots of medication, antibiotics etc... no significant improvement)

These are my preliminary results on the lab test I did in European Laboratory of Nutrients. What is noticeable is the lack of Vitamin D, the glutathione depletion and the blockage of the methylation cycle. Nevertheless a more descriptive interpretation of these results will follow...

I will update this post with the conclusion in the coming days...

HPU Test Keac Laboratories
Carlos Gonzalez
Date 29/04/08
Value Reference Value
Hemopyrrollactamcomplex 0,9 < 1 uMol/L
Slightly Positive in Urine=> (Deficiency of P5P, manganese and Zinc)

ELN European Laboratory of Nutrients
Lab results 6/5/2008
Carlos Gonzalez

Value Reference Units
Elements in hair:

Calcium 1330 200-2000 mg/l
Magnesium 47 25-150 mg/l
Zinc 181 140-240 mg/l
Copper 17 12-60 mg/l
Manganese *0.10 0.15-2.30 mg/l
Selenium 0.66 0.40-2 mg/l
Chromium *0.10 0.15-1.40 mg/l
Cadmiun 0.10 0-0.5 mg/l
Lead 2.90 0-7 mg/l
Mercury *5.2 0-2 mg/l
Nickel 0.4 0-2.1 mg/l
Selenium 0.66 0.40-2 mg/l
Silver 1.57 1-1.9 mg/l
Aluminium 1 0-10 mg/l
Sulphur 49700 40000-60000 mg/l
Phosfor 148 90-180 mg/l
Iron *4.9 5-15 mg/l
Silicium *75.6 4-20 mg/l
Sodium *2 18-90 mg/l

Vanadium 31 9-80 mg/l


Calcium / Magnesium *28.3 5-18
Zinc / Copper *10.6 4-10

Zinc / Cadmium 1810 >400

Saliva tests

Morning cortisol *7 13-24 n/mol
Noon Cortisol *11 5-10 n/mol
Afternon Cortisol 8 3-8 n/mol
Midnight Cortisol 4 1-4 n/mol
DEHA-S *17 3-10 ug/l
Cortisol burden 30 23-42 (in a later analisys fell to 22)

Organic Acids in urine

Lactic acid 42.65 0-10 mmol/mcr
Pyruvic acid 1.24 0-50 mmol/mcr
2-hydroxybutyric acid 0.83 0-2 mmol/mcr
Glyceric acid 1.42 0-10 mmol/mcr


2-hydroxysovaleric acid 0.61 0-2 mmol/mcr
2- Oxoisovaleric acid 0 0-2 mmol/mcr
3-methyl 2- Oxoisovaleric acid 1.96 0-2 mmol/mcr
Hydroxyisovaleric acid 1.07 0-2 mmol/mcr
2- Oxoisocaproic acid 0 0-2 mmol/mcr
2-Oxo 4-Methybutyric acid 0 0-2 mmol/mcr
Mandelic acid 0 0-5 mmol/mcr
Phenyllactic acid 0.20 0-2 mmol/mcr
Phenypyruvic acid 0.42 0-5 mmol/mcr
Homogentisic acid 0.06 0-2 mmol/mcr
4-Hydroxyphenyllactic acid 0.47 0-50 mmol/mcr
Pyroglutamic acid *13.19 20-115 mmol/mcr
3-Indoleacetic acid 3.83 0-10 mmol/mcr
Kynurenic acid 0.46 0-2 mmol/mcr


3-Hydroxybutyric acid 1.21 0-10 mmol/mcr
Acetoacetic acid 0 0-10 mmol/mcr
Ethylmalonic acid 0.92 0-10 mmol/mcr
Methylsuccinic acid 0.96 0-5 mmol/mcr
Adipic acid 0.52 0-12 mmol/mcr
Suberic acid *3.22 0-2 mmol/mcr
Sebacic acid 0.09 0-2 mmol/mcr


Glutaric acid 0.26 0-2 mmol/mcr
Methylmalonic acid *5.49 0-5 mmol/mcr
N-Acetyl-Aspartic acid 0.43 0-3.5 mmol/mcr
Orotic acid 1.64 0-36 mmol/mcr
3-hydroxy-3-methyglutaric acid 1.82 0-20 mmol/mcr
Hydroxyhippuric acid


Cittramalic acid 0.84 0-2 mmol/mcr
5-Hydroxymethyl-2-furoic acid 17.25 0-80 mmol/mcr
3-Oxoglutaric acid 0 0-0.5 mmol/mcr
Furan-2,5-dicarboxylic acid 9.57 0-50 mmol/mcr
Furancarbocinglycine 0 0-60 mmol/mcr
Tartaric acid *30.56 0-16 mmol/mcr
Arabinose 17.65 0-47 mmol/mcr
Carboxycitric acid 0 0-46 mmol/mcr


2-hydroxyphenylacetic acid 0.55 0-10 mmol/mcr
4-hidroxyphenylacetic acid 9.28 0-50 mmol/mcr


DHPPA-analog 19.10 0-150
VMA-analog 2.45 0.31


Succinic acid 3.29 0-20 mmol/mcr
Fumaric acid 0.07 0-10 mmol/mcr
2-oxo-glutaric acid *11.68 15-200 mmol/mcr
Anconitic acid 14.70 0-25 mmol/mcr
Citric acid 518.05 180-560 mmol/mcr


HVA acid 2.12 0-3.5 mmol/mcr
VMA acid *3.69 0-3.5 mmol/mcr
5-hydroxindoleacetic acid 1.04 0-20 mmol/mcr


Uracil 5.89 0-22 mmol/mcr
Thymine 0.31 0-2


Glycolic acid 14.35 0-100 mmol/mcr
Oxalic acid 2.90 0-100 mmol/mcr
Malonic acid 5.67 0-10 mmol/mcr
Methylglutaric acid 0.63 0-10 mmol/mcr
Hyppuric acid 360.89 10-400 mmol/mcr
4-hydroxybutyric acid 1.58 0-5 mmol/mcr
Phenylcarboxylic acid 0.50 0-15 mmol/mcr
Indol-like-compound 0.24 0-60 mmol/mcr

Urine Analysis:

Volume 1850 600-2500 ml
T3 *669 800-1800 pmol/24h
T4 *1664 1800-3000 pmol/24h
T3%mean ref. value 51.5
T3%mean ref. value 69.3
T3/T4 ratio *0.40 0.63-1
Reversed T3 *131 46-130 pmol/24h
T3/RT3 ratio *5.1 10-20
17-ketoSteroid 8.9 7-20 mg/24h
17-OH Steroid 10.4 6-21 mg/24h

Clinical Chemistry:

Malondialdehyde 0.71 <1.75 umol/l
Total homocysteine 5.8 4.5-12.4 umol/l
Lipoprotein A 99 0-300 mg/dl
DHEA Sulphate 3.96 0.94-11.7 umol/l

Glutathione Oxidized 0.49 0.16-0.50 nmol/l
Glutathione reduced 4.2 3.8-5.5 umol/l
Ratio Reducido/Oxidado 6.57 = (4,2-2x(0,49))/0,49


Viatmin A 95 63-115 ug/100ml
Pantotenic Acid (B5) 1056 592-1842 ug/l
Vitamin B6 act (P-5-P) *33.8 13-30 ug/l
Vitamin C 1.36 0.9-2.1 mg%
Viatmin E 1.4 1.3-3.7 mg%
Vitamin D *25.2 32.8-86.8 ug/l

Vitamins: mol/l

Viatmin A 3.3 2.2-4 umol/l
Pantotenic Acid (B5) 4.8 2.7-8.4 umol/l
Vitamin B6 act (P-5-P) *137 48.6-121.4 umol/l
Vitamin C 77 50-120 umol/l
Viatmin E 33 30-87 umol/l
Vitamin D *63 82-217 umol/l

Elements in whole blood:

Sodium 1820 1820-2050 mg/l
Potassium 1860 1670-1970 mg/l
Calcium 51 48-61 mg/l
Magnesium 40.9 34-48 mg/l
Zinc 6 5.3-6.5 mg/l
Copper 0.9 0.8-1.3 mg/l
Selenium 0.139 0.12-0.41 mg/l
Manganese 17.2 14-37 ug/l

Sodium levels are quite low... sodium is involved in carrying nutrients across the cell membrane, neurological signalling and is controlled by adrenal hormones. Low sodium to potassium will create depression, paranoia and other nuerological issues. Low sodium is generally the result of an adrenal situation

Elements in serum:

Magnesium 21.3 19-24 mg.l
Zinc 0.9 0.8-1.4 mg/l
Copper 1 0.7-1.4 mg/l

Intracellular concentration:

Zinc 12 10.5-13.7 mg/l
Magnesium 63.9 52-80 mg/l
Copper 0.8 0.7-1.3 mg/l
Zinc/Copper ratio 15 9-16

Biological Amines:

Serotonin 40.8 30-400 ng/10E10

Miscellaneous: (Methylation panel)

S-Adenosylmethionine (plasma) 93.4 82.7-156 nmol/l
S-Adenosylmethionine (RBC) 241 221-256 umol/dl
S-Adenosylmethionine (WBC) *3.7 3.9-8 cells
S-Adenosylhomocisteine (plasma) *39.7 21-35 nmol/l
S-Adenosylhomocisteine (RBC) *52.3 38-49 umol/dl


5-CH3-THF 8.7 8.4-72.6 nmol/l
10-FORMIL-THF *1 1.5-8.2 nmol/l
5-FORMIL-THF *0.83 1.2-11.7 nmol/l
THF 0.76 0.6-6.8 nmol/l
Folic Acid 10.2 8.9-24.6 nmol/l
Folinic Acid (WB) *1.4 9-35.5 nmol/l
Folic Acid (RBC) *305 400-1500 nmol/l

Plasma Nucleoside
Adenosine *37.5 16.8-21.4 10^-8M

Aminoacids Urine 24h

Phosphoserine 55 28-91 umol/24h
Taurine 905 220-1292 umol/24h
Phosphoethanolamine 40 19-55 umol/24h
Aspartic Acid *153 29-149 umol/24h
Hydroxyproline 32 0-54 umol/24h
Threonine 153 83-321 umol/24h
Serine 382 132-580 umol/24h
Asparagine 130 66-306 umol/24h
Glutamic Acid 29 10-58 umol/24h
Glutamine 455 109-551 umol/24h
Sarcosine <1 0-2 umol/24h
α amino adipic Acid *57 9-51 umol/24h
Proline 14 0-35 umol/24h
Glycine 1429 380-2432 umol/24h
Alanine 355 141-491 umol/24h
Citrulline 5 0-28 umol/24h
α aminobutyric acid 19 11-35 umol/24h
Valine 46 10-54 umol/24h
Cystine 30 21-83 umol/24h
Methionine 51 16-62 umol/24h
Cystathione 19 15-75 umol/24h
Isoleucine 14 5-33 umol/24h
Leucine 39 11-51 umol/24h
Tyrosine 95 40-168 umol/24h
B Alanine *61 0-51 umol/24h
Phenylalanine 37 31-95 umol/24h
Beta Aminoisobutyric Acid 63 0-208 umol/24h
Homocystine (free) 3 0-4 umol/24h
Gamma-Aminobutyric Acid 11 7-35 umol/24h
Ethanolamine 277 146-352 umol/24h
Hydroxylisine 18 0-22 umol/24h
Ornithine 19 6-38 umol/24h
Lysine 99 76-336 umol/24h
1 Methylhistidine *504 128-392 umol/24h
Histidine 805 103-1207 umol/24h
Tryptophane 55 31-101 umol/24h
3 Methylhistidine 253 73-301 umol/24h
Anserine *48 0-46 umol/24h
Carnosine 70 0-98 umol/24h
Arginine 22 7-39 umol/24h
Volume 1850 600-2500 ml

Klinische Chemie:

DHEA Sulphate 3.99 0.94-11.7 umol/L
Cortisol 0.28 0.14-0.69 umol/L

Inhalent panel IgE

TREE / SHRUB (*Out of reference range)
Alder White
American Beech
American Hazel Nut
Elm mix
Oak Black
Sycamore Eastern

Bermuda grass
Jhonson grass
Rye grass
Timothy grass
Ragweed western


Ragweed, western

Cockroach german

Food Intolerances IgG

No apparent food intolerances on the test! In the past I had many... probably because I killed all the parasites: Giardia, Entamoeba hystolitica, etc... I only have blastocystis Hominis at the moment.

S-adenosylhomocysteine is a more sensitive indicator of renal insufficiency than homocysteine; also appears to be a more sensitive indicator of the risk for cardiovascular disease than is homocysteine.

Based on the results of this Nutritional Profile, the supplements recommended are the following:

Suprasquash 2-3 capsules/day
Glutathion 150 mg or increase NAC dose 1-2 capsules/day
Magnesium taurate Plus (incl.B6) 2-3 capsules/day
Vitamin B2 - active 1 capsule/day
GTF chromium 50mcg 2 tables/day
Multivitamin 2 capsules/day
Manganese 1 tablet/day
Folinic/Folic acid 0.8-2 mg/day
B6/12/folic acid formula 1 capsule/day
Maybe also TMG/Bataine/Choline or lecithine: omnicholine 2-3 capsules/day

Apply with meals divided over the day. Start each product in lowest dose. Gradually increase on daily basis until the above mentioned rage has been reached. Consider testing vitamins and minerals 4-6 months after start supplements.

Supplements available at vital cell life, ask for 25% price reduction
Phone +31302871008

This supplements still have to be approved by my immunologist Josepa Rigau.



Manganese (Mn)

Adequacy assessment: RBC Mn; BUN, urinary ammonia markers, arginine/ornithine ratio
Optimal forms: Sulfate, lactate, succinate, gluconate and citrate salts
Clinical indications: Deficiency: increased oxidative activity, Toxicity: neurotoxicity, including parkinsonism
Food sources: Tea, whole grains, legumes, nuts, green vegetables

The average adult contains 10 to 12 mg total-body manganese (Mn),32 primarily concentrated in tissues requiring high energy, including brain, and also found in liver, pancreas and kidney.432 Manganese is a group VII transition metal, existing in a number of different oxidation states, but in biological systems, the most prevalent are +2 and +3.

Chemically, manganese is similar to iron, so an imbalance in one may induce imbalance in the other. For example, iron deficiency may increase manganese transport, both in the GI and CNS, creating the potential for a toxic manganese burden.

Manganese is a cofactor for enzymes involved in metabolism of amino acids, lipids and carbohydrates. Manganese-dependent enzyme families include oxido-reductases, transferases, hydrolases, lyases, isomerases and ligases. Examples of manganese-containing enzymes are arginase, glutamine synthase and mitochondrial superoxide dismutase (referred to as SOD2 or MnSOD).

Physiological activities include immune function, regulation of blood sugar and cellular energy, reproduction, digestion, bone growth, and protection from oxidative challenge. Manganese with vitamin K supports blood clotting and hemostasis.

Clinical Associations of Manganese

Change in CNS manganese tissue concentration may be accompanied by convulsions. Both high and low blood manganese has been associated with seizure disorders. In one reported case, a 3-year-old child presented with idiopathic seizure disorder.

The only abnormal findings were elevated blood manganese and encephalopathy on EEG. The patient, who was non-responsive to antiepileptic medication, deteriorated to status epilepticus. Immediate resolution was attained upon administration of IV Ca-EDTA therapy. Exposure to welding done by her father over 1 month was the reason for the child’s manganese burden.

Increased activity in MnSOD with concurrent reduction in cytosolic SOD (which is copper and zinc dependent) was demonstrated in vitro after cellular gamma ray irradiation exposure, demonstrating that MnSOD assessment may be a biomarker of radiation sensitivity, as well as illustrating the import of MnSOD in radiation-induced tissue damage.
Iron overload disorders such as Friedreich’s ataxia (FA), sideroblastic anemia (SA) and hemochromatosis demonstrate reduced activity of MnSOD.

Both FA and SA present with increased iron deposition in mitochondria. FA, a neurodegenerative and myocardial disease, is caused by decreased expression of the iron-regulating mitochondrial protein, frataxin. Low frataxin causes iron overload and manganese depletion, greatly reducing MnSOD activity. In a frataxin-deficient yeast model, manganese was shown to increase MnSOD, whereas a MnSOD mimetic showed little effect. These iron-overload conditions require increased antioxidative support as afforded by MnSOD.437-441 Manganese may be a worthy treatment consideration in such disorders.

High doses of N-acetylcysteine was shown to induce formation of manganese superoxide dismutase in vitro, thereby preserving its activity. Women demonstrate increased absorption of manganese and increased MnSOD activity mediated by estrogen, which may exert antioxidant effects by this mechanism.

All forms of SOD are down-regulated in estrogen deficient mice that also show increased vascular free radical activity. Progesterone has been shown to reduce SOD activity, and thus antagonize the vasoprotection induced by estrogen. These findings may in part explain why hormone replacement therapy with estrogen plus progesterone displayed no beneficial effect on cardiovascular event rates in prospective clinical

Frank manganese deficiency in humans to date has been studied only by chemically induced manganese depletion. However, individuals with low manganese intake have impaired growth, poor bone formation and skeletal defects, reduced fertility and birth defects, abnormal glucose tolerance, and altered lipid and carbohydrate metabolism. Men experimentally placed on manganese-depleted diets developed a rash on their torsos, and women consuming < 1 mg manganese/d in
their diet developed altered mood and increased pain during premenstruation.

Arginine converts to either ornithine or citrulline, producing urea or nitric oxide (NO), respectively. Inhibition of arginase reduces conversion of arginine to ornithine and promotes conversion into citrulline, thereby increasing NO production (and decreasing urea production). Because manganese is the cofactor for arginase, lowered plasma manganese correlated with lower arginase activity and corresponding increased nitric oxide production in patients with childhood asthma.

Similarly, manganese deficiency in rats enhances endothelium-dependent vasorelaxation of aorta. Arginase inhibitors are being considered as potential interventions for increasing nitric oxide.

Toxic effects of inhaled manganese in dust or aerosols have been reported from occupational exposure in welding or steel alloy production. Toxicity via ingestion, primarily from water sources, has also been reported.

Total parenteral nutrition is a potential iatrogenic route of toxic exposure to manganese. Manganese is being considered as an additive for gasoline, as a lead replacement. Although it has been shown to greatly improve oil combustion, attention must be given to the potential for increased exposure.

Vegetarianism may increase manganese body burden via increased dietary consumption and/or iron deficiency-induced increased manganese absorption. Soy beverages, including infant formula, have been shown to contain 100-fold greater amounts of manganese than human milk, and 10-fold greater amounts than bovine sources. Studies using soybased formulas in primates show increased incidence of behavioral disorders. However, soy is rich in phytates that inhibit absorption of manganese as well as other elements. Thus, vegetarians eating large amounts of soy may, paradoxically, develop manganese deficiency. Since bile is the main route of manganese elimination, individuals with liver disease frequently present with higher levels of manganese, and therefore are at greater risk of toxicity.

The organ most vulnerable to manganese toxicity is the brain. Manganese concentrates in areas with high iron, including the caudate-putamen, globus pallidus (GP), substantia nigra and subthalamic nuclei. The neurotoxicity of manganese appears to be mediated by the oxidation of divalent to highly oxidative trivalent manganese via superoxide, inducing a cascade of oxida-
tive mediators damaging cellular components, primarily in the mitochondria. Chronic, low-level exposure to manganese has been implicated in neurologic changes, decreased learning ability in school-aged children, and increased propensity for violence in adults.

Frank manganese toxicity, “manganese madness,” presents similarly to schizophrenia. Symptoms include compulsive or violent behavior, emotional instability, hallucinations, fatigue and sexual dysfunction.Mechanistically, this initial presentation is likely due to lesions in the GABAergic neurons of the globus pallidus.

As the condition progresses, damage to the dopaminergic neurons in the substantia nigra causes a clinical presentation similar to parkinsonism, but differentiable by the presense of dystonia induced by GP lesions. Furthermore, manganese-induced dopaminergic neuronal oxidation caused general derangements in the hypothalamic-pituitary-adrenal (HPA) axis, including abnormal serum prolactin, TRH, FSH and LH. Additionally, excess manganese can inhibit astrocyte glutamate reuptake, thereby increasing glutamate’s excitotoxic potential, and its time in the synapse.

Clinical efficacy has been demonstrated for EDTA chelating therapy in a case of occupational parkinsonism due to manganese exposure. Improved clinical pattern due to reduction of heavy metal deposition in basal ganglia was confirmed by MRI.

Occupational exposure to manganese compounds in this case resulted in high blood and urinary levels of the metal.
Manganese enters the CNS and is absorbed along the length of the small intestine through the divalent metal transporter 1 Maximal GI absorption is about 3%. Since iron shares the same transporter, increased manganese GI absorption and CNS delivery has been shown to occur in iron deficiency states, contributing to increased manganese burden.

Conversely, manganese absorption is decreased in the presence of iron. Excretion is primarily via bile to feces, with minimal elimination in urine. Phytates may inhibit absorption, and reducing dietary manganese and increasing biliary elimination further decrease manganese in the body.32, 100 Given the similarity manganese has with iron, it may be that similar counter-ions would increase GI bioavailability, including sulfate, gluconate and citrate.

Manganese is rapidly cleared from blood and stored in liver and other organs.32 In plasma, manganese is largely bound to gamma-globulin and albumin, with a small fraction of trivalent manganese bound to the iron-carrying protein, transferrin.
Assessing Manganese Status Some review articles have concluded that there is no reliable index or biomarker for evaluating manganese insufficiency. Others have concluded that of the direct biomarkers used, RBCs are best associated with long-term levels and are considered to be a good index of manganese status. Manganese is frequently measured in profiles of trace elements in RBCs or whole blood where low levels are found in manganese-depleted individuals.

A number of studies examining normal or deficient manganese in a variety of human populations have relied on erythrocyte measurements. Such findings may be combined with other functional markers known to appear abnormal when manganese insufficiency is affecting metabolic activity. Altered plasma concentrations of ammonia and urea are found in association with decreased hepatic manganese concentration in young growing rats.465 Thus, serum BUN and sensitive urinary markers of urea cycle activity may be helpful along with demonstration of an elevated plasma arginine-ornithine ratio to achieve an assessment of low manganese effects.

Hair manganese is a valid indicator of toxicity in cases of manganese excess, but there is controversy over its use for deficiency states.Inconsistent results have been reported from studies using plasma, serum or urine to evaluate manganese status.Because of its strong paramagnetic quality and primary site of toxicity in the CNS, manganese toxic burden is readily assessed using T1-weighted MRI. RBC manganese demonstrates a high correlation with MRI (r = 0.55, p = 0.02) in manganese-exposed workers prior to onset clinical symptoms. Additionally, RBC manganese was shown to correlate specifically with CNS globus pallidus burden. RBC and MRI manganese assessment also correlated in liver cirrhosis patients.

Manganese Repletion Dosing Bioavailable forms of managnese include sulfate, lactate, succinate, gluconate and citrate. Dosing range is 5 to 13 mg/d for adults residues on thyroglobulin and is responsible for phenoxy-ester bond formation between the rings of monoiodo-L- tyrosine (MIT) and diiodo-L-tyrosine (DIT) to form T3 and T4 on Tgb. Afterwards, lysozome-mediated hydrolysis liberates the iodinated compounds from Tgb. MIT and DIT are recycled and T3 and T4 are released into the bloodstream. Peripheral conversion of T4 to the metabolically active T3, and subsequent breakdown of T3, requires the selenoproteins476 iodothyronine deiodinases (D1 and D2).32 Similarly, the deiodinases work inside the follicular cell to recycle tyrosine and iodine.

Chromium (Cr)

Adequacy assessment: RBC, whole blood, urine, hair; Insulin, blood glucose
Optimal forms: Nicotinate, chloride, histidine or picolinate salts
Clinical indications of deficiency: Blood sugar dysregulatory conditions
Food sources: Whole grains, legumes, nuts, yeast, meats

Unlike most essential elements that have multiple metabolic functions, the only known role for chromium
(Cr) is in potentiating insulin receptor tyrosine kinase This autoamplification allows chromium to exert broad influence on carbohydrate, lipid and protein metabolism. Total-body chromium concentration is only about 4 to 6 mg, and decreases with age.

There are small chromium storage pools in the testes, kidneys and spleen. Trivalent chromium is the only oxidation state required in biological systems. Hexavalent chromium is a well-known carcinogen that is particularly associated with lung tumor induction.

Clinical Associations of Chromium
Chromium and insulin work in tandem. When insulin is released into circulation, chromium transport to insulin-sensitive cells is increased. Once inside the cell, chromium acts as an autoamplifier of the insulin receptor tyrosine kinase. However, chromium is a nutritional double jeopardy. It is known to be removed from some carbohydrates during the refinement process,
making it less available during the insulin rise. It has also been demonstrated that increased urinary wasting of chromium occurs in conditions of elevated blood glucose and insulin. Thus, consuming refined carbohydrates exacerbates losses of chromium and induces insulin resistance.

In the 1950s, rats on a chromium-deficient diet were found to have reduced ability to remove glucose from blood. Subsequent research demonstrated that chromium transport and cellular uptake is stimulated by the presence of insulin. Chromium is delivered to insulin-sensitive cells on the iron-binding transport protein transferrin. In the cytosol, it is theorized that chromium complexes with apochromodulin, inducing a conformational change, which creates active chromodulin.

Chromodulin is a protein that is rich in cysteine, glycine, glutamate and aspartate residues and tightly binds four ions of trivalent chromium. It is also referred to as low-molecular-weight chromium-binding substance (LMWCr), and is similar in structure to yeast glucose tolerance factor (GTF). Chromodulin dramatically increases the tyrosine kinase activity of the insulin
receptor, thereby inducing downstream events stimulated by insulin. For example, chromium supplementation enhanced translocation to the plasma membrane of glucose transporter 4 protein in insulin-resistant animals. Once blood insulin levels drop, the insulin receptors undergo a conformational change that allows for the release of chromodulin, which is then apparently expelled from the cell and eliminated in urine. However, in cases of insulin resistance, with increased concentra-
tion of blood glucose and insulin, there is a paradoxical urinary wasting of chromium, most likely in the form of chromodulin.
Since chromium is integral to insulin signaling, all insulin-mediated metabolic events improve with identification and correction of chromium insufficiency.

Chromium-induced improvements have been demonstrated in type 2 diabetes, including improved lipid and carbohydrate metabolism, reduced blood insulin and glucose, and reduced body weight.607 Chromium supplementation has shown efficacy with atypical depression, illustrating a link between blood sugar, insulin and mood. Both gestational and steroid-induced diabetics have demonstrated positive response to chromium supplementation. Chromium use in individuals exhib-
iting no blood sugar irregularities has no demonstrated beneficial effect.Hexavalent chromium (Cr VI) is 1,000 times more
toxic than trivalent chromium (Cr III). In addition to its carcinogenicity, topically, hexavalent chromium is an irritant, causing severe dermatitis. Cr VI is still widely used in industry, and is present in cigarette smoke, paint pigment, chrome plating, leather tanning, metal pros-theses and copy-machine toner.609 Microflora appear to participate in the reduction of hexavalent chromium to trivalent chromium, minimizing the effects of toxic exposure.

Contamination of ground water with hexavalent chromium, and the associated morbidity and mortality to residents of the area resulted in the largest settlement paid in a direct action lawsuit in US history and was the subject of the film Erin Brockovich.
Jejunal absorption is inversely related to dietary intake, but is generally quite low, ranging from 0.5 to 2%. Similar to iron, chromium absorption is inhibited by phytates and enhanced by ascorbic acid. There appears to be competition by other elements, including iron, zinc, manganese and vanadium. Excretion is via both renal and fecal routes.

Chromium appears in urine primarily as chromodulin. There is a lag time between oral ingestion of chromium and appearance in urine, indicating incorporation into chromodulin prior to excretion. Elevation of glucose and insulin lead to increased excretion of chromium, as chromodulin. The Fe-transport protein, transferrin, appears to maintain Cr3+ levels in the blood plasma and to transport Cr to tissues in an insulin-responsive manner.

Assessing Chromium Status
Total-body chromium is so low that analytical issues have limited accurate direct measures of the element. However, instrumentation advances such as the addition of the dynamic reaction cell (DRC) filters for inductively coupled plasma mass spectrographic (ICP-MS) methods allow accurate detection of chromium in urine, serum and whole blood. The DRC adaptation removes interfering argon carrier gas atomic species, largely eliminating interferences that have compromised chromium
measurements in the past. While methodology has improved, chromium levels in states of insufficiency differ depending on matrix and physiological conditions, resulting in inconsistencies that appear to greatly complicate interpretation.

Erythrocyte chromium has been used to assess excessive levels of exposure in workers exposed to chromate. When exogenous chromium contaminationis limited, hair continues to be a viable specimen option for establishing long-term chromium status.
Given the difficulties with interpretation of direct chromium concentration measurements, functional evidence for dysglycemia, such as elevated blood glucose and insulin levels, or an abnormal glucose-insulin tolerance test can provide a functional assessment of chromium insufficiency. Thus far, the reversal of symptoms with chromium supplementation is currently
the only generally accepted indicator of chromium deficiency.

Since chromium is excreted as the insulin-stimulated metalloprotein chromodulin, urinary chromium presents a special situation, where levels may provide a type of functional assessment because of the high percentage that is excreted in the form of chromodulin.

Further research into the interpretation of fasting and non-fasting urinary chromium levels is warranted. When exogenous chromium contamination is limited, hair continues to be a viable specimen option for establishing long-term chromium exposure. An abnormal glucose-insulin tolerance test may provide a functional assessment of chromium insufficiency.

Chromium Repletion Dosing
Chromium picolinate (200–100 µg) is an effective supplementation for treating diabetes and weight gain from insulin insensitivity. Chromium picolinate may function similarly to chromodulin. The form derived from yeast called chromium-glucose tolerance factor (GTF), the glutathione-dinicontinate complex similar to the chromodulin complex, is not effectively
absorbed. The chromium-histidine complex appears to be highly bioavailable.

Mercury (Hg)

Toxicity symptoms: Mental symptoms (erethism, insomnia, fatigue, poor short-term memory), tremor, stomatitis, gingivitis, GI and renal disturbances, decreased immunity Body burden assessment: Whole blood, erythrocyte, serum, hair, urine, urinary porphyrins
Protective measures: Selenium (protects against cellular toxic effects)
Chelating agent: DMSA, DMPS
Common sources: Dental amalgams, fish consumption, preservatives (esp. thimerosal), industrial relaease

Mercury (Hg) as a neurotoxin has an intriguing history. The phrase “mad as a hatter” has its origins with the seventeenth and eighteenth century hat makers who suffered from mercurialism due to their use of liquid mercury in the manufacture of the popular felt-brimmed hats. Sir Issac Newton, the famous seventeenth century physicist, experienced a year of dark moods and marked personality change that puzzled friends and close associates.

Posthumous analysis of archived samples of Newton’s hair revealed highly elevated concentrations of mercury, which is evidence that supports the historical hypothesis that Issac Newton’s “madness” was a result of his exposure to the toxic metal while he was conducting experiments to study its properties. The human population is exposed daily to naturally occurring mercury. The earth’s crust releases approximately 30,000 tons of mercury per year as a product of natural outgassing from rock. Mining, smelting and combustion of fossil fuels, particularly coal, are a primary source of anthropomorphic mercury exposure.

Approximately 6,000 tons/year of mercury are used in the manufacture of electrical switches, for electrolysis, and as a fungicide. Ninety tons of mercury are used each year for making dental amalgams. According to the CDC, mercury released from amalgams may comprise up to 75% of an individual’s mercury exposure.

The amount of mercury released from amalgams ranges between 1.2 to greater than 27 µg/d. Toxicity associ- ated with mercury amalgams continues to be a serious concern, particularly in regard to pregnant women, as mercury is a known neuroteratogen.

In its elemental form, mercury (Hg0) is non-toxic. However, once chemically or enzymatically altered to the ionized, inorganic form (Hg2+), it becomes toxic. Thus, bioconversion of mercury to its organic alkyl forms renders some forms such as methyl mercury highly toxic with great avidity for the nervous system.

Another commonly encountered organomercury compounds is ethylmercury that is released from thimerosal. Microorganisms in the environment and in the human intestinal tract can bioconvert non-toxic elemental mercury to inorganic Hg2+ and organic mercurous alkyl compounds.

Methylmercury is highly water soluble and readily enters aquatic food chains, accumulating at higher concentrations in the tissue as it moves up the food chain of marine organisms. Bioaccumulation of methylmercury in organisms at the top of the aquatic food chain is on the order of 10,000 to 100,000 times greater than concentration in the ambient waters.Indeed, methylmercury from seafood is considered to be the most important source of non-occupational human mercury exposure.

Analysis of commercial fish in New Jersey markets found bioaccumulation to be the highest (in descending order of magnitude) in yellow fin tuna, Chilean sea bass, bluefish and snapper.

Thimerosal has been widely used to preserve vaccines used for immunizations. The mercury thioether structure of thimerosal can be metabolized or chemically degraded to release the much more toxic ethylmercury.

Although lack of data makes precise comparisons of safe levels of exposures to different forms of mercury difficult, we may gain insight about the potential for toxic effects from the available data on mercuric chloride, ethylmercury and methlmercury. Thimerosal, a mercury-containing preservative used in vaccines, has been a common source of mercury exposure for children.

In the human body, thimerosal releases ethylmercury. In 2002, it was demonstrated that the mean total mercury dose in vaccines received by 6-month-olds was 111.3 µg (range 87–175 µg).In a 6.2 kg infant, 111.3 µg translates to 18 µg/kg/d or about 2.6 times the adult minimal risk level (MRL) of 7 µg/kg/d for acute mercuric chloride exposure.

The US Environmental Protection Agency (EPA) sets a reference dose (RfD) of 0.1 µg/kg body weight/d for chronic exposure to methylmercury, at which there are no recognized effects. Using the EPA’s RfD, a vaccination containing 111.3 µg mercury would expose a 6.2 kg infant to 29 times the safe level for chronic methylmercury exposure. Based on such inferences, governmental health authorities now advocate removal of thimerosal-containing childhood vaccines.

Clinical Associations of Mercury Toxicity
There are three known ways by which toxic effects are produced by mercury: (1) It reacts with sulfhydryl groups impairing the activity of enzymes, (2) it generates protein adducts that are immunogenic, and (3) its highly lipophilic alkyl forms alter nerve membrane function.Autoimmune glomerulonephritis in mercury-exposed individuals has suggested an association between exposure and autoimmunity in humans.

Mercury intoxication, in turn, can produce a triad of symptoms: (1) mental changes, (2) spontaneous tremor and deficits in psychomotor performance, and (3) stomatitis and gingivitis. The mental effects include erethism (excessive irritability, excitability or sensitivity to stimulation), depression, short-term memory loss, difficulty concentrating, insomnia and fatigue. Additional signs of neurotoxicity include loss of vision, hyperreflexia, sensory disturbances, imparement of speech and hearing, hyperhidrosis and muscular rigidity. Signs and symptoms of mercury intoxication involving other organ systems include renal and gastrointestinal disturbances, pain in joints and limbs, weight loss, metallic taste in the mouth and increased susceptibility to infections.

Mercury released from dental amalgams, which are composed of as much as 50% mercury, can have a negative impact on an individual’s health. Although mercury-containing amalgams have been in use for over 100 years, their use was intensely debated at the turn of the century and again in the 1930s. Small yet measurable amounts of mercury are continuously released from the amalgam surface; the rate of release is accelerated by hot liquids and chewing. Normal bacterial flora converts a fraction of the released elemental mercury to its toxic forms, Hg2+ and alkyl mercury. A portion of the elemental mercury released from amalgams is unavoidably inhaled into the lungs, where it can be biotransformed to its toxic forms. Studies have suggested that chronic mercury exposure in amounts released by amalgams provokes an increase in both mercury- and antibioticresistant strains of bacteria in the oral and intestinal flora.

Such mercury-induced aquired resistance to antibiotics has been found worldwide in fish and soil bacteria. Epidemiologic data from the US EPA and CDC have led to estimates that more than 300,000 newborns each year may have increased risk of learning disabilities associated with in utero exposure to methylmercury.

Chinese children with both inattentive and combined attention deficit hyperactivity disorder (ADHD) have blood mercury levels higher than controls. Risk of ADHD was found to be nearly 10 times higher when blood mercury was above 29 nmol/L. With the pronounced rise in the incidence of autism over the last decades, much debate continues regarding mercury’s role in the pathogenesis of this neurodevelopmental condition. Although research does point to the eitiology of autism being multifactorial, numerous reports demonstrate that aspects of mercury toxicity appear similar to autism symptomatology.

In 2002, thimerosal was phased out of some vaccines, as recommended by the US Public Health Service and the American Academy of Pediatrics. Data from the Vaccine Adverse Event Reporting System (VAERS) reported a significant reduction in the proportion of neurodevelopmental disorders, including autism, mental retardation and speech disorders, as thimerosal was removed from childhood vaccines in the United States from mid-1999 onward. As of the date of this writing, since regulations do not govern all sources, vaccines must still be verified as thimerosal free.

In addition to the previously discussed nutritional factors, gender and age can also influence mercury status and toxic consequences. In an Austrian population with generally low levels of mercury, values in males were influenced by fish intake, amalgam fillings, age and education level, whereas those for females varied only with dietary fish intake, indicating gender-specific effects. In older Americans, visual memory ability declines as blood mercury levels rise, although other neurological tests such as finger tapping were uaffected.867

Assessing Mercury Body Burden and Toxic Effects
A primary function of the clinical laboratory is to assist clinicians in making decisions about when to treat a patient for heavy metal toxicity. However, there is considerable debate over how to establish reference limits for mercury (and other toxic metals) on clinical laboratory reports. The US EPA RfD for chronic mercury exposure of 0.1 µg/kg/d is equivalent to a total exposure of 7 µg/d in a 70 kg adult. If the amount of mercury absorbed from dental amalgams is combined with all other sources of mercury (e.g., fish, environmental, occupational and medicinal), the daily exposure to mercury is expected to exceed the RfD for some individuals.In populations such as occupationally exposed workers and the elderly, the percentage of mercury-threatened individuals can be much higher.

Based on a study of normal, presumably healthy populations, mean wholeblood mercury concentration was found to be < 5 µg/L. About 1% of this population had whole-blood levels of mercury greater than 5 µg/L. Individuals with occupational exposure to mercury, such as dentists and dental technicians, may routinely have whole-blood mercury up to 15 µg/L. Significant exposure is evident when whole-blood alkyl mercury is greater than 50 µg/L, or when Hg2+ exposure is greater than 200 µg/L. Based on the first German Environmental Survey on Children, lowering of reference values for whole-blood mercury from 1.5 to 1.0 µg/L has been proposed.

Consumption of large amounts of fish by pregnant women in Hong Kong results in prenatal exposure to moderately high levels of mercury shown by finding cord-blood mercury levels above 29 nmol/L (5.8 µg/L) in newborn infants. A separate study found that, compared with the national average, women who ate fish were 3 times more likely to have elevated cord-blood levels. Of the 275 women who completed the study, 28.3% had cord-blood mercury above the 5.8 µg/L reference level set by the EPA. In a random sample of 474 subjects in Baltimore, Maryland, 9% had blood mercury levels above the 5.8 µg/L limit. However, elevated levels (> 5.8 µg/L) are found in 16.5 % of women in populations with high fish consumption.

Blood mercury has revealed low level chronic and acute exposure from work environments, whereas elevations of mercury have been reported as high as 16,000 µg/L in blood and 11,000 µg/L in urine. At massive elevation levels, interpretation is straightforward, allowing assessment of patient exposure factors and clinical consequences. As with most tests performed on a broadly varying outpatient population, interpretation of results from measurements of mercury in blood or urine become more difficult as concentrations approach the population norms of 10 to 20 µg/L.

Concurrent or follow-up testing of biomarkers that show toxic consequences, such as elevated porphyrins, beta-2-microglobulin or N-acetyl-beta-D-glucosamine can be very helpful.

The level of mercury in urine is a reliable way to assess exposure to inorganic mercury. Daily urinary levels greater than 50 µg indicate a Hg2+ overload. Hair levels of mercury greater than 1 µg/g also indicate mercury toxicity. The quantity of mercury assayed in blood and hair, but not urine, correlates with the severity of toxicity symptoms.

Erythrocyte mercury shows a strong relationship with erythrocyte selenium, suggesting a chemical linkage between the two elements. Erythrocyte mercury was strongly correlated with plasma mercury, and both mercury and selenium levels were strongly correlated with fish intake.Hair has been a frequently used specimen by CDC and EPA for accurately assessing mercury exposure in selected populations.A number of studies have shown positive associations between mercury concentrations in blood and hair. Hair to blood ratios ranging from 200 for maternal hair-cord blood to 360 for hair-blood values in 7-year-old children have been reported. Populations of Brazilian communities showed a positive correlation of blood pressure with levels of hair mercury. At levels above 10 µg/g, the odds ratio for elevated systolic blood pressure was 2.9.

Both blood and hair mercury levels drop between the second and third trimesters of pregnancy. Maternal hair correlates with cord blood, both levels being related to fish intake. Measurement of mercury concentrations in body tissues or fluids provides evidence of exposure, but it does not answer the question of toxic effects that are dependent on many other factors. Variations in status of thiols such as glutathione, cysteine or lipoic acid shift the dynamics of mercury’s effects, as do the levels of metallothionein, zinc and selenium, or even glutamine. Specific patterns of urinary porphyrin abnormalities have been clearly associated with mercury, providing a convenient and sensitive biochemical marker of metabolic toxicity.

Management of the Mercury-Toxic Patient
Removing the source and optimizing routes of mercury elimination should be the first treatment for mercury toxicity. Antioxidant intervention may be helpful for mitigating the oxidative damage caused by mercury toxicity. Some antioxidants such as N-acetyl- cysteine, alpha-lipoic acid and glutathione may posess chelative effects. Selenium has been demonstrated to effectively bind mercury, rendering the mercury ineffective (see the section “Selenium” above). More aggressive treatment for mercury toxicity calls for chelation therapy.

Administration of BAL, penicillamine, EDTA, DMSA or DMPS will mobilize mercury and cause a rise in the daily urinary mercury excretion rate. The preferred chelation agents, based on their affinity for mercury and low toxicity, are DMSA or DMPS.2 All of these agents should be used with monitoring of mercury metabolic toxicity, since they can mobilize relatively inert bound forms of mercury. If porphyrin profile signs start to worsen, treatment may need to be suspended until newly mobilized mercury reaches equilibration with metallothionein and other routes of binding for excretion.

Removing brain accumulations of mercury is a challenge. DMSA and DMPS may not be effective agents for removing toxic metals found in the CNS, as they are very unlikely to cross the blood-brain barrier. It has been suggested that alpha-lipoic acid may cross the blood-brain barrier, and combinations of ascorbic acid and glutathione may help to allow mercury transport away from tissues by altering the ionic form. However, when combinations of these interventions were tested in mercury-exposed rats, no reduction in brain mercury was found.

Of Further Interest…

Toxic element accumulation is dependent on route and duration of exposure, form of toxic element and presence of protective measures. For example, rats maintained for 18 months on low-selenium diets and consuming drinking water containing 5.0 ppm of mercury as methylmercury had 10-fold higher mercury in brain compared with those given water with 0.5 ppm mercury. However, brain mercury increased only slightly in similarly exposed rats fed diets with high selenium content (0.6 vs. 0.06 ppm), and no increase was seen at lower levels of exposure, showing the protective effect of dietary selenium.

Another important observation from these experiments was that mercury was higher in neonatal rats that also had lower retention of selenium, and blood and brain mercury levels fell with age as selenium levels stabilized. Such results raise timing issues and possible protective measures. Administration of vitamin C, glutathione or lipoic acid in combination with DMPS or DMSA to young rats for 7 days following a 7-day exposure to elemental mercury vapor had no effect on brain mercury.

Here, the toxic element form was elemental versus methyl mercury, and administration was by inhalation for 7 days rather than ingestion for 18 months. The protective measures were administered for only 7 days and only after exposure had occurred. Longer-term administration of the protective nutrients might produce quite different results, especially if tissue levels are raised before exposure. Kidney mercury in the rats exposed to mercury vapor was lowered by DMPS and DMSA, but no combination was found to affect levels in brain.

These results provide insight about differences in tissue distribution and ligand character. In metallothionein-rich kidney tissue, bound mercury is more dissociable than that bound to enzymes in the brain. Such differences among tissues in their sequestration tendencies leads to concern about potential redistribution induced by therapies that cause mobilization of toxic metals. Thus mercury released from extrahepatic tissues might transfer to brain as a result of chelation therapies. Very little is known about how much such redistribution actually occurs for any given chelator. Such effects may account for the suggestions that treatments of past mercury exposures with N-acetylcysteine or reduced glutathione may be counterproductive.

For toxic elements other than mercury, the constant redistribution over time produces an accrual in bone, where they are bound in the hydroxyappetite matrix. These forms are of lower concern (and low contribution to laboratory element testing) until they are remobilized during bone resorption. Such issues complicate the evaluation and treatment of patients with toxic element effects.

Sodium (Na)

Sodium (Na) along with chloride comprise the major electrolytes of the body’s extracellular fluid (ECF). Sodium deficiency is rarely considered outside of unusual circumstances of losses due to vomiting and diarrhea or sweating. In such cases, the imbalance in ECF and intracellular fluid (ICF) allow water to pass into the cells in excess, leading to symptoms of water toxicity, including apathy, muscle twitching and loss of appetite. When both sodium and water are lost, total blood volume decreases, causing hypotension, tachycardia and other heart disturbances. Prolonged imbalances in ECF and ICF can become serious emergencies.

Excessive sodium intake is widely considered to be a risk factor in certain cases of hypertension, and frequent monitoring with 24-hour urinary sodium measurements is recommended to help educate patients who need to lower sodium intake. Magnesium deficiency has been demonstrated to impact electrolytes, including sodium, potassium and calcium.

Iron (Fe)
Adequacy assessment: Ferritin, hemoglobin, hematocrit, total iron binding capacity, transferrin saturation
Iron excess: Transferrin saturation
Optimal forms: Ferrous gluconate, fumarate, and citrate salts; combine with ascorbate
Clinical indications of deficiency: Fatigue, delay in growth or cognitive development, weakness, arthralgias, organ damage
Food sources: Organ meats, brewer’s yeast, wheat germ, egg yolk, oyster, dried beans, and some fruits

It has been estimated that 6 of 100 Americans are in negative iron balance, whereas 1 of 100 have iron (Fe) overload. Iron overload can be caused by a common genetic disorder in the United States. There are only about 2.5 to 4 grams of iron in the healthy human body, yet this element has critical functions, and the human body has an intricate system of maintaining homeostasis.

Human understanding of iron and anemia has a long history, and therefore a wealth of information is available on its absorption, transport, storage and biochemical roles, as well as appropriate laboratory evaluation.

Hemoglobin contains 70% of total-body iron. Another 3.9% is found in myoglobin and in mitochondrial proteins involved in energy metabolism and respiration such as cytochromes, catalase, peroxidase and metallo-flavoprotein enzymes. Plasma iron is largely bound to transport proteins (mainly ferritin, transferrin and albumin), leaving only 0.1% of total-body iron as free
iron in plasma.

Dietary sources of iron include heme iron (meat) or non-heme iron (iron-rich plants), which is less bioavailable. Homeostasis of iron is carried out by up- or down-regulation of transferrin and ferritin receptors on cell surfaces to balance absorption, storage, circulation and excretion of iron. Absorption of non-heme iron is mediated by the divalent metal transporter 1 DMT1, among others. This transporter is up-regulated in iron deficiency.

Toxic elements such as cadmium and lead share the same transporter, and it may be the reason that iron deficiency predisposes humans to cadmium and lead toxicity. By the same token, an iron-replete diet may protect from other element toxicities. There is no mechanism to excrete excess iron by the body, though small amounts of iron are lost through urine, bile and sloughing of intestinal mucosal cells in the feces. This loss amounts to less than 1 mg/d, so the daily need of iron is about 1 to 1.5 mg for healthy adults. The RDA is much higher, reflecting low GI absorption of iron in healthy individuals. Premenopausal women are subject to a much greater loss of iron during menstruation.

Toxic elements can “piggy back” on the homeostatic mechanisms for iron regulation and can pose a second adverse consequence for the patient with either extremely high iron stores or for the patient with iron deficiency.

DMT1 mediates absorption of iron, manganese, cadmium, and lead,98 and some toxic elements use transferrin as their carrier protein (e.g., aluminum). Iron Deficiency Anemia Iron deficiency anemia (IDA) has effects on tissue and cardiac health, physiological growth, productivity, maternal and fetal mortality, cognitive development, and attention span. Although hemoglobin (Hb) is routinely measured to monitor the critical stages of anemia, Hb is not the most sensitive marker of iron deficiency which advances in stages, starting with decreased iron stores (ferritin) and ultimately ending in effects on erythrocytes.

β-Amino Acids
β-Amino acids are so named because their amino groups are attached to the beta carbon. These com- pounds are not found in proteins. They serve physiological functions ranging from bile acid precursor and antioxidant to neurotransmitter and metabolic control.
They can be acquired from the diet or synthesized de novo. Taurine is a β-amino acid, but was also discussed under the sulfur amino acids. Taurine and the other β-amino acids use the same carrier-mediated active transport into cells.


β-Alanine is released from skeletal muscle during strenuous exercise and it occurs in food mainly as carnosine in red meats or anserine in poultry. The pyrimidines cytosine and uracil from DNA and RNA are degraded to β-alanine.

β-Alanine can become elevated in plasma or urine due to enzyme deficiency, dietary intake, intestinal microbial overgrowth, or high turnover of muscle tissue

β-Alanine has been used as an index of carnosine catabolism. Deficient activity of the enzyme β-alanyl-a-ketoglutarate transaminase in a 4-year-old girl was corrected by oral pyridoxine therapy in one reported case. Intermittent seizures and lethargy were reduced. The biochemical pathway involved in this case is the conversion of β-alanine to a-ketoglutarate
Vitamin B deficiency generally causes lowered activity of the enzymes that degrade β-alanine, resulting in high urinary excretion. High β-alanine is frequently associated with generalized β-aminoaciduria and concomitant loss of other amino acids such as taurine, due to impairment of renal tubular resorption. Low taurine levels may indicate taurine depletion by this
mechanism. High levels of β-alanine are frequently accompanied by increases in 1- and 3-methyl-histidine, carnosine and anserine.

Uptake of taurine occurs by a carrier-mediated active transport process specific for β-amino acids. Because there is transporter competition for β-amino acid entry into cells, excessive taurine administration may cause elevated carnosine (resulting in muscle weakness) or elevated β-alanine.486 Therefore, monitoring β-alanine levels can help the clinician appropriately adjust taurine supplementation. Use of taurine should be decreased when β-alanine is elevated. Excess excretion of taurine may indicate β-aminoaciduria. β-Alanine impairs renal tubular resorption of a variety of amino acids, including taurine, thus propagating amino acid deficiencies

The origins and dispositions for β-alanine are quite different from those for alanine discussed previously. At cell death, DNA
catabolism releases β-alanine from breakdown of cytosine. Dietary carnosine and anserine are normally hydrolyzed rapidly
with release of β-alanine. β-Alanine is used for synthesis of muscle carnosine and for ubiquitously distributed coenzyme A that is required for multiple central energy pathways. Excess β-alanine is oxidized via conversion to acetate.

Epileptic patient treatment with the GABA transaminase inhibitor, vigabatrin, produces elevated β-alanine because the drug also blocks its breakdown.I did take Gabapentine in high dose 3 years ago, I wonder if that matters.

Intestinal bacteria and/or Candida albicans can also make β-alanine, which can raise plasma levels of β-alanine. With high β-alanine, check urinary indican or other dysbiosis markers as a measure of bowel dysbiosis. A bowel detoxification program may be appropriate with supplementation of a high-potency Lactobacillus acidophilus and L. bifidus products along with prebiotics and a high-fiber diet to support growth of the favorable organisms. Because of the competition of β-alanine for the taurine transporter, a bowel detoxification program to remove a major source (microbial overgrowth) of β-alanine can help to raise the kidney threshold to taurine spill and, therefore, help raise plasma taurine levels.

Suplements taken during the last 4 months (not the week previous to blood and urine test)

2LCMV (Antiviral Homeopatico para el CMV) daily only first 10 days of the month
2LEBV (Antiviral homeopatico para el EBV) daily

Glutamine: Every Morning
L-Glutamine 5,000 mg **
N-Acetyl D Glucosamine 200 mg **
Gamma Oryzanol 125 mg **
Proprietary Herbal Blend 75 mg **
Cranesbill Root (Geranium maculatum) **
Ginger Root (Zingiber officinale) **
Marigold Flower (Calendula officinalis) **
Marshmallow Root (Althaea officinalis) **

Citrobiotic: Grape Fruit seeds extract every morning

B6+Magnesio (Oral Flash): daily in the morning
B6 1,5mgr
Magnesio 250mgr

Body Bio Balance Oil: with meals
Linoleic omega 6 8,3gr
Linoleic omega 3 2,1gr
Linoleic omega 9 1,9gr

Probiotics: a lot, changing brands every month

Antibiotics: in the last 4 months before this test was done, only once cefalosporina for a Haemofilus Parainfluenza infection.

5-HTP: just occasionally
Magnesium 50mg
5HTP (L-5 Hydrotryptophan from griffonia simplicifolia seed extract) 100mgr
Valerian Root podwer extract 100mgr
Vitamin B6 (as Pyridoxine hydrochloride P-5-P) 10mgr

Ergytaurina: once a day with meals

Taurina 120mgr
Glutation 3mgr
Metionina 30mgr
Zinc 3,5mgr
Sulforafano 150 ug
B6 800 ug
B9 100 ug
Selenio 25 ug

MVM-A: twice a week a multivitaminic ( Dr. Pall supplements)

Vitamin C 67 mgr
Vitamin D3 267 IU
Vitamin K1 25 mcg
Thiamin 8mgr
Riboflavin 10 mgr
Niacin 18 mgr
B6 8 mgr
Folic Acid 400 mcg
B12 30 mcg
Biotin 100 mcg
Panthotenic Acid 20 mg
Calcium 83 mg
Iodine 50 mg
Zinc 40 mg
Selenium 67 mcg
Copper 0,4 mg
Manganese 1,5 mg
Chromium 50 mcg
Glycine 8 mg
Strontium 7 mg
Taurine 83 mg
Aceyil L Carnitine 100 mg
Lipoic Acid 40 mg

CoQ Gamma E: Daily ( Dr. Pall supplements)
Vitamin A 6980 IU
Vitamin C 34 mg
Vitamin E 47 IU
Mixed Tocotrienols and Tocopherols 20mg
DeltaGold Tocotrienols 80mg
Gamma Tocopherol 200mg
Mixed Carotenoids 6mg
Lycopene 6mg
Lutein 6mg
Coenzyme Q10 150 mg
Alph Lipoic Acid 18mg

NAC: Daily ( Dr. Pall supplements)
N-Acetyl L-Cyseine 200mg
Trimethylglycine 300mg
Ribonucleic Acid 120mg
Alpha Lipoic Acid 100mg

FlaviNox: Daily ( Dr. Pall supplements)
Milk Thistle 80mg
Bilberry 100mg
Ginko 40mg
Grape Seed Extract 100mg
Green tea extract 80mg
Cranberry Juice 100mg
Hawthorn extract 100mg

Carnitine 1gr daily, before the test, and currently 3 gr daily after seeing Dr. Kurk and getting prescription.

L'equilibre Vital: only when my PH is unbalance
Citrato de potasio 65mg
Citrato de sodio 40mg
Citrati de Calcio 23,3mg
Citrato de hierro 1,16 mg
Citrato de manganeso 0,16 mg

Candi Bactrin: Only 21 days durin March to try to get rid of Blastocystis Hominis (did not work)
Coptis Root (Containing berberine) & Rhizome 30mg
Oregon Grape Root 4:1 Extract (Berberis aquifolium) 70mg
Berberine Sulfate 400mg

For digestions:
Artichoke extract 400gr
Cardo Mariano (Milk Thistle)
Enzymes: amilasa, lipasa, lactasa, etc...