Tetracycline Antibiotics Are Strong Iron Chelators

haidut

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Excess iron is implicated in virtually all chronic pathologies as well as a number of acute infections. Ray has written about this and mentioned that phlebotomy is one good way to reduce iron overload. He also mentioned that coffee is another good method. However, one of these methods is impractical (phlebotomy) for most people and the other (coffee) is not very effective as chlorogenic acid has relatively weak iron chelating activity.
It appears that the tetracycline family of antibiotics, and especially doxycycline, are very strong iron chelators. According to this study, this chelating ability explains at least in part their antibiotic activity. Given the prominent role of iron in cancer, the iron chelation ability would also explain some of the benefits of tetracyclines in cancer. Peat wrote that W. Koch considered tetracyclines a viable approach in treating/managing cancer.
Anyways, if this is true then it should be a good method for people to lower iron load.

http://aac.asm.org/content/44/3/763.full

"...A strong iron-chelating activity for doxycycline and minocycline and a less pronounced one for tetracycline were detected using a siderophore colorimetric assay. Ferrichrome, the positive control, reduced the initial absorbance by approximately 50% when used at a concentration of 25 μg/ml, while doxycycline and minocycline reached a comparable decrease at 250 μg/ml and tetracycline reached a comparable decrease at a concentration of >1,000 μg/ml. Penicillin G, gentamicin, clindamycin, spiramycin, and metronidazole did not show any iron-chelating activity."

"...In this study, we showed that tetracyclines possess a strong iron-chelating activity. This property appears to be unique, since none of the other antibiotics tested showed this capacity to chelate iron. Previous reports have indicated that tetracyclines form complexes with metallic cations, including iron (20, 25, 26). A number of studies have also revealed that tetracyclines possess a strong capacity to inhibit the activity of matrix metalloproteinases (MMPs) (5, 8,9). This inhibition appeared to be related to a chelating property, since it could be reversed by the presence of an excess of calcium. "
 

jyb

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But wouldn't they chelate other importance things like zinc too? For antibtiotics I think I worry more about effects on the gut flora.

A number of studies have also revealed that tetracyclines possess a strong capacity to inhibit the activity of matrix metalloproteinases

Could that be a bad thing? At least, not as bad as broader MMP inhibitors:

Wikipedia: Matrix metalloproteinase
Pharmacology

Doxycycline, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. It is used clinically for the treatment of periodontal disease and is the only MMP inhibitor that is widely available clinically. It is sold under the trade name Periostat by the company CollaGenex. Minocycline, another tetracycline antibiotic, has also been shown to inhibit MMP activity.

A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies that MMPs are suspected to be involved in (see above). However, most of these, such as marimastat (BB-2516), a broad-spectrum MMP inhibitor, and cipemastat (Ro 32-3555), an MMP-1 selective inhibitor, have performed poorly in clinical trials. The failure of Marimastat was partially responsible for the folding of British Biotech, which developed it. The failure of these drugs has been due largely to toxicity (in particular, musculo-skeletal toxicity in the case of broad spectrum inhibitors) and failure to show expected results (in the case of trocade, promising results in rabbit arthritis models were not replicated in human trials). The reasons behind the largely disappointing clinical results of MMP inhibitors is unclear, especially in light of their activity in animal models.
 

haidut

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jyb said:
But wouldn't they chelate other importance things like zinc too? For antibtiotics I think I worry more about effects on the gut flora.

A number of studies have also revealed that tetracyclines possess a strong capacity to inhibit the activity of matrix metalloproteinases

Could that be a bad thing? At least, not as bad as broader MMP inhibitors:

Wikipedia: Matrix metalloproteinase
Pharmacology

Doxycycline, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. It is used clinically for the treatment of periodontal disease and is the only MMP inhibitor that is widely available clinically. It is sold under the trade name Periostat by the company CollaGenex. Minocycline, another tetracycline antibiotic, has also been shown to inhibit MMP activity.

A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies that MMPs are suspected to be involved in (see above). However, most of these, such as marimastat (BB-2516), a broad-spectrum MMP inhibitor, and cipemastat (Ro 32-3555), an MMP-1 selective inhibitor, have performed poorly in clinical trials. The failure of Marimastat was partially responsible for the folding of British Biotech, which developed it. The failure of these drugs has been due largely to toxicity (in particular, musculo-skeletal toxicity in the case of broad spectrum inhibitors) and failure to show expected results (in the case of trocade, promising results in rabbit arthritis models were not replicated in human trials). The reasons behind the largely disappointing clinical results of MMP inhibitors is unclear, especially in light of their activity in animal models.

Yeah, I think there is a concern that tetracyclines will chelate not just iron but many other metals as well. When I was prescribed doxycycline years ago, the doctor told me to drink trace mineral solution and an electrolyte drink like Gatorade.
 

Fletcher

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Can anyone help me with what a dose of 250 μg/ml of doxycycline would be in mg?
 

paymanz

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Yeah, I think there is a concern that tetracyclines will chelate not just iron but many other metals as well. When I was prescribed doxycycline years ago, the doctor told me to drink trace mineral solution and an electrolyte drink like Gatorade.
But that lowers tetracyclines bioavailability.
 

paymanz

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Maybe if your forced to eat a high iron food and you have excess iron in your body then tetracyclines are good tools to prevent iron absorption ,if taken with meal.

But otherwise, as @jyb mentioned ,it can chelate other minerals too ,which sounds bad.

I would like to know what minerals binded to tetras the most? With what dosage and to what degree?

Also does tetracycline metal complex still has antibiotic function?!
 
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