The first time someone told me that metformin depletes B12, I thought they were describing a bug in a system that should have been caught. Someone is prescribing a medication for insulin resistance — one of the most commonly prescribed drugs in the world — and that medication, over time, progressively reduces absorption of a vitamin required for mood, cognition, and nerve function. And the conversation about this is happening mostly in nutritional medicine, not in the standard prescribing workflow.

B12 deficiency looks like depression. It looks like fatigue. It looks like cognitive fog and poor concentration and low energy. If you are on metformin and have been for years, and you are experiencing these things, and no one has tested your B12, there is a conversation that should be happening that may not be.

This is not a reason not to take metformin. It is a reason to eat eggs regularly, to eat animal protein, and to talk to your prescriber about annual B12 testing.

Every medication that changes how your body processes or absorbs things changes the nutritional math. Valproate depletes carnitine and folate — and folate depletion from valproate is particularly serious for anyone who might become pregnant, because folate deficiency and neural tube defects have a documented relationship. The prescription should come with the supplement recommendation. Often it doesn't.

SSRIs and 5-HTP: SSRIs work by blocking serotonin reuptake. Adding a serotonin precursor in supplemental doses — 5-HTP, St. John's Wort — stacks serotonergic activity in a way that can trigger serotonin syndrome. This is documented. It is a real risk. Most people don't know it because they found 5-HTP on a wellness website that didn't mention it.

Stimulants and vitamin C: Amphetamines are excreted more rapidly in acidic urine. Vitamin C acidifies urine. If you take Adderall in the morning with orange juice, the orange juice is reducing the efficacy of the medication. The prescriber increased the dose. You take the larger dose one day without the juice. The dose is now too high.

Lithium and sodium: These two compete for reabsorption in the kidneys. When sodium intake drops — whether from a low-salt diet, heavy sweating, vomiting, or the first weeks of a ketogenic diet — the kidneys compensate by reabsorbing more lithium. Blood lithium levels rise. This can tip from therapeutic to toxic rapidly. The symptoms of lithium toxicity are serious. This is not a theoretical risk. It is basic renal physiology, and it is the most important reason that anyone on lithium needs to discuss any significant dietary change with their psychiatrist before making it.

I am not telling you these things to frighten you away from medication. Medication works. For a lot of people, medication is the reason they can function. What I'm saying is that medication does not operate in a nutritional vacuum, and the food you eat is part of how your medication does or doesn't work. That relationship deserves to be managed, not ignored.

Beckie knows these interactions. They are the first layer she checks when you tell her what you're on.