Overloading syndrome

Kollef MH, McCormack MT, Caras WE, Reddy VV, Bacon D. The fat overload syndrome successful treatment with plasma exchange. Ann Intern Med 1990 112(7) 545-6. 

Under normal circumstances, transferrin is one-fourth to one-third saturated with iron. The level of saturation may decrease in systemic infection or cancer and in iron deficiency anemia, the most common nutritional deficiency in the United States. In individuals with iron deficiency anemia, transferrin levels are increased. The level of saturation with iron increases in iron overload syndromes such as hereditary hemochromatosis or as a result of repeated blood transfusions, as is the case in thalassemia patients. Determinations of total plasma iron (TI) and plasma total iron binding capacity (TIBC) are routinely performed in the clinical biochemistry laboratory. The TIBC value reflects transferrin levels in plasma the amount of iron that can be bound by transferrin is equal to TIBC x 0.7. Total plasma iron levels in iron deficiency anemia become abnormal before hemoglobin levels show any change. 

Common problems in the past were fat overload syndrome, metabolic acidosis, hyperglycemia, and hypertriglyceridemia (6). These problems are now rare. Increasing efforts have been made to avoid adverse effects such as central venous catheter infection and hepatic dysfunction. Major developments in the future are likely to be achieved with the identification of nutrients, hormones, or other active compounds that can positively influence outcome beyond the safe provision of 40 essential nutrients in proper amounts, which is what principally has been achieved to date (7). Liver damage is still a major problem. The most common micronutrient deficiency is of thiamine. 

Infection has long been recognized as a risk of parenteral nutrition and it has proved impossible to eliminate it (SEDA-22, 379). Once established, sepsis can increase the risk of fat overload syndrome. In an extensive study in Taiwan there was sepsis with positive blood cultures in 56 of 378 children receiving parenteral nutrition the risk factors were longer duration of parenteral nutrition, age under 3 months, the use of central venous catheters, gastrointestinal disease as an indication for parenteral nutrition, low birth weight, and short gestational age in prematurity (128). 

Acute hepatitis mimicking iron overload syndrome was reported in a 35-year-old man who had been taking fo-ti (dose and duration unspecified). Laboratory studies included alanine transferase 2714 U/1 (normal <50 U/1), aspartate aminotransferase 1170 U/1 (normal <50 U/1), AP 137 U/1 (normal <130 U/1), total bilirubin 4.6 mg/dl (normal <1.4 mg/dl), direct bilirubin 3.0 mg/dl (normal <0.4 mg/dl), and ferritin 13,862 ng/ml (normal 8 to 282 ng/ml) and a fasting transferrin saturation of 86% (normal 20% to 60%). Analysis of the herbal supplement identified extracts from fo-ti including the anthraquinones emodin and physcion. The patient recovered after cessation of the herbal products, and liver function tests 4 months after hospitalization were normal (Laird et al. 2008). 

Laird, A.R., N. Ramchandani, E.M. Degoma, et al. 2008. Acute hepatitis associated with the use of an herbal supplement (Polygonum multiflorum) mimicking iron-overload syndrome. /. Clin. Gastroenterol. 42(7) 861-862. 

In dog toxicity tests over a four-week period with a dose of fat of 9 g kg day" S the following adverse signs were observed marked anemia and leukocytosis, hypertriglyceridemia, vomiting, diarrhea, and blood in urine and faeces (Jacobson and Wretlind 1970). This clinical picture may be explained by extensive and disseminated fat embolism (Obel 1970). These adverse reactions, which are reversible up to a certain grade of severity, would correspond to the late reactions or fat overloading syndrome observed in humans. 

While chemical principles can be used to design chelators that form stable and specific Fe chelates, uncertainty about the nature and location of the chelatable iron pool and constraints on delivery of suitable chelators to the site of action have determined that iron chelator design is still dominated by empirical testing of structure-function relationships. This in itself adds a new challenge in that there is no perfect animal model for the human iron overload syndromes. Pitt (1981) has pointed out that rodents Fe-loaded with heat-damaged erythrocytes have been used most frequently to assess the ability of chelators to remove iron by the fecal (biliary) and urinary routes and lower parenchymal (liver) and RES (splenic) stores. He reviews LD50 and iron-removal data on many natural and synthetic hydroxa-mates, phenols, catechols, tropolones, salicylates, benzoates, azines, and carboxylates. No clear picture emerges and the search for the ideal iron chelator continues. 

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