Same as for my last post, I will simply give quotes from the article below (PDF)1. Also, the article is from 2007 so I will repeat a more in-depth search in a second post.
Repleted iron stores and preceding high iron intakes reduce intestinal iron absorption which, however, offers no reliable protection against oral iron overload.
Iron-related harm can be due to direct intestinal damage, to oxidative stress, or to stimulated growth of pathogens.
With regards to iron, intestinal barrier function exceeds absorptive functions, so that the major fraction of ingested iron remains in the intestinal lumen. Intracellular labile iron concentration in different tissues is also homeostatically regulated. Labile iron (which in some related publications is termed ‘‘free iron’’) in this context encompasses all iron species that are not firmly bound to ligands with a high complex formation constant and, therefore, may participate in undesired redox processes with a potential to cause harm.
Moreover, iron deficiency compromises cellular immunity. Neutrophilic function decreases with decreasing activity of iron-dependent myeoloperoxidase, so that intracellular bactericidal activity is impaired. Proliferative response and the number of T lymphocytes are decreased and natural killer cell activity, lymphocyte IL-2 production and macrophage migration factors are impaired, while humoral defence is not affected.
Excessive intracellular iron is taken up into ferritin, an oligomeric protein of 24 identical (or similar) subunits with a molecular weight of approx. 500 kDa that can sequester up to 4500 iron ions per molecule in a nontoxic but bioavailable form. The function of ferritin is to limit the size of the potentially harmful intracellular ‘‘labile iron pool’’ ( ¼ LIP) and, in parallel, to store iron in a form that can be mobilised in situations of scarcity to replace losses and, thus, to reduce the risk of iron deficiency.
High iron status was related to a plasma-lipid composition with an unfavourable cardiovascular risk profile.
Moreover, the capacity of the regulatory mechanisms iron absorption to prevent iron overload is overwhelmed, e.g. at iron intakes over 30 mg Fe/d in the elderly.
Therefore, the US-FNB proposed to base dietary iron requirements on a well-defined iron status and to choose 15 mg/L as the lower cut-off point for serum ferritin concentrations. Iron stores above this value are regarded as sufficient to guarantee adequate iron supply to erythropoiesis and were also used by FAO/WHO and the EU Scientific Committee for Food (SCF). The RDA thus derived is not meant to build up iron stores. Explicitly, the US Food and Nutrition Board (FNB) attributed no physiological benefits to iron stores higher than the minimum. to guarantee adequate iron procurement to the functional compartmentsFood ligands like ascorbic acid, polyoxycarbonic acids such as citrate and malate, and the digestion products of meat, fish or poultry enhance iron absorption, while, e.g. phytic acid in grains and legumes, polyphenols in tea and coffee, or calcium inhibit it.The interaction between iron and food ligands seemed to be lesser when studied over extended periods than in single meal studies, this review, however, is not shared by all researchers, and was not adopted by FAO/WHO. The absorption of haem iron from meat, fish, and poultry is much less affected by dietary components with the exception of calcium.To estimate the average response of iron bioavailability to all these factors, a number of algorithms was developed and iron bioavailability was set as 5% for a strict vegetarian diet, as 10% when some meat and ascorbic acid was added, and as 15% for diets rich in meat and fruitsIron was classified with the nutrients in the high risk group by the German Federal Institute for Risk Assessment. Iron has a potential to cause direct erosion and irritation of the gastrointestinal mucosa, to cause oxidative damage of lipid membranes, proteins or DNA (see section ‘‘Iron homoeostasis and the potential of iron to cause harm’’). In addition, iron can stimulate inflammation or, as an essential nutrient, fertilise the growth of pathogens Due to this potential, iron may mediate damage in the intestinal lumen, the vascular compartment, the cells, and the interstitial space.LD50 ( ¼ median lethal dose) values for Fe (II)-sulphate, -succinate and -gluconate after single oral doses in mice are 560, 320 and 230 mg Fe/kg body weight, respectively. A similar ranking of iron-induced damage by compounds was observed in male rats after repeated oral application of 50 and 100 mg Fe/kg body weight for 12 weeks, and for the emetic impact and gastrointestinal damage in cats and rabbits. The mechanisms of iron homoeostasis and the kind of damage observed in rodents and men are similar. However, considerable differences were found in the quantitative aspect of iron kinetics between men, rats and mice, and even between different stains of mice. This makes quantitative extrapolation of animal data to humans difficult if not impossible.Fractional iron absorption after oral intake amounts to 10–20% or less. Thus, 80–90% of ingested iron remains in the gut lumen and may cause considerable harm by different mechanisms at toxic and therapeutic dose levels.Overdoses of oral iron preparations cause mucosal erosions in stomach and intestine. Blood-containing vomiting and diarrhoea are the first symptoms of acute iron intoxication, followed by a ‘‘silent interval’’ of up to 24 h. Gastrointestinal strictures are possible long-term sequels of such damage and may require surgical intervention. Oral doses of 180–300 mg Fe/kg body weight can be lethal to humans; oral doses below 10–20 mg Fe/kg body weight do not cause acute toxicity and seem to present a NOAEL for these effects.The discussion on possible iron effects on cardiovascular risk is highly controversial which, in part, is due to the difficulty to differ between cause and effect in the underlying pathogenic feed-back cycles. Even a significant correlation between atherosclerosis and serum ferritin leaves open whether ferritin represents high iron stores, or if it is increased in response to the inflammatory impact of atherosclerosis. Thus, a cause–effect relationship can neither be proven nor rejected.The discussion started with the observation of a 2.2-fold increase in relative risk for acute myocardial infarction ( ¼ AMI) in East Finland at serum ferritin concentrations above 200 mg/L. Such ferritin levels are found in approx. 18% of males in the US and Europe. Follow-up studies showed conflicting outcomes.In most subsequent studies cardiovascular risk correlated with body iron stores, though significance was frequently not reached, not even when corresponding data were subject meta-analysisThe growth of pathogenic bacteria depends on the ability to acquire iron from their hosts. Conversely, one of the host’s defence strategies is to limit iron availability, e.g. by binding iron tightly to transferrin and lactoferrin. This reduces labile iron in the plasma to a concentration below 1018, which is insufficient for bacterial growth. Moreover, haemopexin and haptoglobin limit the availability of haem and haemoglobin as an alternative iron source for extracellular bacteria.