Iron, calcium and levothyroxine: the medications food and supplements interfere with

Drug interaction warnings tend to focus on the dramatic — the combinations that cause bleeding, arrhythmia or serotonin syndrome. Those matter. But a quieter category causes a great deal of avoidable trouble: interactions that simply prevent a drug from being absorbed.

These produce no symptoms of their own. What they produce is an apparent treatment failure, and the usual response to apparent treatment failure is to increase the dose.

Levothyroxine

The clearest example. Absorption is impaired by a long list of common items, and the effect is substantial rather than marginal.

Calcium and iron supplements bind levothyroxine in the gut. So do some antacids and phosphate binders.

Proton pump inhibitors reduce absorption by raising gastric pH.

Coffee reduces absorption measurably — studies have found reductions of around 30 per cent when taken together, which is not trivial.

Soy products and high-fibre meals also interfere.

The practical rule: take levothyroxine on an empty stomach with water, at least 30 to 60 minutes before food or coffee, and separate calcium and iron by at least four hours. Consistency matters as much as timing — taking it the same way every day produces stable levels even if the way is imperfect.

An unexplained rise in TSH in a stable patient is more often an absorption problem than a thyroid one, and is worth investigating before increasing the dose.

Bisphosphonates

Oral bisphosphonates such as alendronate have famously poor bioavailability — under 1 per cent absorbed under ideal conditions, and essentially zero if taken with food, coffee, juice or mineral water.

They must be taken on waking, with a full glass of plain tap water, remaining upright and taking nothing else by mouth for at least 30 minutes. The upright requirement is about oesophageal irritation rather than absorption, and it is not optional — bisphosphonate-induced oesophagitis can be severe.

The regimen is demanding enough that adherence is poor, which is part of why intravenous zoledronic acid once a year is an attractive alternative for many older patients.

Antibiotics

Tetracyclines and fluoroquinolones both chelate divalent cations. Taking ciprofloxacin with a glass of milk, an antacid or a calcium supplement can reduce absorption enough to cause treatment failure — which then looks like antibiotic resistance.

Separate by two hours before or four to six hours after.

Levodopa

Levodopa competes with dietary amino acids for the same transporter across the gut wall and the blood-brain barrier. A high-protein meal can therefore blunt or delay the effect of a dose, producing fluctuations that patients experience as unpredictable off periods.

Taking levodopa 30 to 60 minutes before meals helps. In more advanced disease, protein redistribution — shifting most protein intake to the evening — is sometimes used, though it needs dietetic supervision because older adults with Parkinson's are already at risk of undernutrition and sarcopenia.

The interactions that are dangerous rather than merely ineffective

Grapefruit juice inhibits intestinal CYP3A4, raising blood levels of a range of drugs — some statins (simvastatin and atorvastatin particularly), some calcium channel blockers, some immunosuppressants. The effect can last more than a day, so separating the timing does not help.

Vitamin K and warfarin. The issue is not that green vegetables are forbidden; it is that intake should be consistent. A sudden change in either direction destabilises the INR.

St John's wort induces liver enzymes and reduces levels of a long list of drugs, including warfarin, some antidepressants, digoxin and several cardiac drugs. It is bought without prescription and rarely disclosed.

Potassium-based salt substitutes with ACE inhibitors, ARBs, potassium-sparing diuretics or aldosterone antagonists — risk of dangerous hyperkalaemia.

NSAIDs with an ACE inhibitor or ARB plus a diuretic — the triple whammy, a well-recognised cause of acute kidney injury in older adults, and easily triggered by ibuprofen bought for a sore knee.

What to do

Take everything to your next review — prescriptions, over-the-counter medicines, herbal preparations and supplements, in their actual boxes. Pharmacists are the best-placed professionals for this and are consistently under-used; in many countries a medicines-use review is free and can be requested directly.

And if a medication seems to have stopped working, consider whether anything about how you take it has changed before assuming the dose is wrong. The answer is quite often a new supplement, a new antacid, or a change in when the morning coffee happens.