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Consulting Pathologist: Dr D. Dean FUNCTIONAL LIVER DETOXIFICATION PROFILE (FLDP) Reference Ref. Range Ref. Range % Recovery RESULTS LEGEND
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FUNCTIONAL LIVER DETOXIFICATION PROFILE (FLDP) INTERPRETIVE GUIDE Phase 1 Interpretation (Caffeine Clearance) The Cytochrome P450 enzymes are the predominant enzyme system involved in Phase I liver detoxification. Their role is to convert toxic substances into more water soluble molecules, so they can be further metabolised in Phase II. Result Possible Cause Treatment Considerations
Excessive cytochrome P450 induction from exposure to: Alcohol, nicotine, caffeine, stress
Drugs - steroids, sulphonamides, barbiturates, HRT
High Phase 1
Toxins - exhaust fumes, paint fumes, dioxin and
Reduced activity of cytochrome P450 from
Low Phase 1
Drugs - benzodiazepines, antihistamines, ketoconazole,
fluconazole, erythromycin, SSRIs, H2 blockers
Glutathione & its precursors (glycine,
Intermediate Phase Interpretation When Phase I activity is high, there is increased metabolic activity at the intermediate phase (before the molecules are presented to Phase II for conjugation). This results in an increased production of free radicals and the potential for secondary tissue damage. It is therefore essential that adequate antioxidants are available to counteract this high free radical activity. Treatment Considerations for the Intermediate Phase Vitamins A, C and E, Co-Enzyme Q10, Zinc and Selenium Phase II Interpretation Phase II reactions involve the addition of a small polar molecule to the substance, a conjugation step that may or may not be preceded by Phase I. Several types of conjugation reactions occur in the body, including glutathionation, sulphation, glucuronidation and glycination conjugation. These reactions require nutrient cofactors, which are essential for proper detoxification.
Prolonged stress on a particular Phase II pathway will cause an increase in free radical damage which, in turn, will reduce liver function in the long term. Low Phase II - indicates down regulation of one or more conjugation pathways resulting in inadequate Phase II conjugation reactions. High Phase II - indicates excessive conjugation of individual or all biochemical pathways, resulting in an increased concentration of metabolic products.
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FUNCTIONAL LIVER DETOXIFICATION PROFILE (FLDP) Pathway Responsible for Conjugation of Treatment Considerations Glutathionation
dependant on the tripeptide glutathione Paracetamol
Individuals with diagnoses of arthritis,
diabetes or heart disease may have lower Tetracycline
Sulphation
Sulphation is ‘rate limited’ by the amount
(aromatic hydroxyl groups including histamine,
Catecholamines (adrenalin, noradrenalin)
Glucuronidation
Estimated to account for 33% of all drugs
Vitamin B complex Essential Fatty Acids
Glycination
*Calcium d-glucurate is metabolised to d-glucaro-1, 4-lactone (glucaro lactone GL). GL is a direct inhibitor of beta-glucuronidase, an enzyme found in the gut that cleaves bound oestrogens and carcinogens from their Phase II conjugates and permits reabsorption through the entero-hepatic circulation. By inhibiting beta-glucuronidase activity, GL increases the net elimination of carcinogens, toxins and steroid hormones via glucuronidation. Sulphate:Creatinine This reflects the level of sulphur available from dietary sources and should be considered in conjunction with the Phase II sulphation result. Phase I:Glycination and Phase I:Glucuronide These two ratios reflect the relationship between Phase I and these conjugation pathways and will demonstrate whether the biochemical load from Phase I is high or low. Sulphate:Glucuronide This ratio reflects the relationship between sulphate and glucuronide. Sulphate is often up regulated to compensate for low glucuronide. Phase I:Sulphation This reflects the relationship between Phase I and the sulphation pathway and demonstrates whether the biochemical load from Phase I is too high.
Note: When all the ratios are high in an FLDP report, this commonly reflects a patient who is highly sensitive and may have multiple food and chemical sensitivities.
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Department of Strategy and PolicyNational University of Singapore15 Kent Ridge DriveSINGAPORE, 119245Ph.D. (Economics), Indiana University, April, 2005M.A. (Economics), Indiana University, February, 2003M.Sc (Management), National University of Singapore, September, 2000B.E. (Management), Peking University, 1998Associate Professor (with tenure), Department of Strategy and Policy, National Uni
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F S C I E N C E SIssue: Cooley’s Anemia: Ninth Symposium Treatment options for thalassemia patients with osteoporosis Evangelos Terpos1 and Ersi Voskaridou21Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. 2Thalassemia Center, LaikonGeneral Hospital, Athens, GreeceAddress for correspondence: Evan