Why Do TTR Silencers Require Vitamin A Supplements?

If you are taking a TTR silencer therapy—such as patisiran, inotersen, vutrisiran, or eplontersen—you are required to take a daily Vitamin A supplement because these medications inadvertently remove your body’s natural transportation system for Vitamin A ^[1][2][3].

The Biology: Transthyretin and Vitamin A

To understand why this happens, it helps to look at the name of the protein itself. Transthyretin (TTR) gets its name from its main job in the body: it Transports thyroxine (a thyroid hormone) and retinol (Vitamin A). Under normal circumstances, the TTR protein safely carries Vitamin A through your bloodstream so it can be delivered to tissues that need it, like your eyes.

TTR silencer medications are designed to drastically reduce the liver’s production of the TTR protein, which is necessary to stop the toxic amyloid buildup that causes ATTRv amyloidosis ^[4][5]. However, by severely reducing the amount of TTR in your blood, the medication also eliminates the primary carrier for Vitamin A ^[1][2][3]. Without its dedicated transport protein, Vitamin A is quickly lost from the bloodstream, leading to a significant drop in Vitamin A levels ^[2][6].

The Risk: Night Blindness and Eye Health

Without consistent supplementation, the sharp drop in Vitamin A puts you at a high risk for developing a deficiency ^[2]. Vitamin A is absolutely essential for maintaining healthy vision, particularly the cells in the retina that allow you to see in low-light conditions.

A severe deficiency can lead to ocular issues, most notably nyctalopia (night blindness), which makes it difficult or impossible to see in the dark ^[7][8]. It can also cause severe dry eyes and physical damage to the structures of the retina ^[7][9]. Fortunately, if these vision issues occur, they are often reversible when caught early and treated with proper Vitamin A supplementation ^[10][11]. If you notice any changes in your low-light vision, tell your doctor or ophthalmologist right away.

Managing Your Supplementation Safely

Because the risk to your vision is significant, clinical guidelines mandate daily Vitamin A supplementation for anyone on a long-term TTR silencer (often around 2,500 to 3,000 IU/day, depending on the specific drug) ^[2][6].

When managing your supplements, keep the following safety guidelines in mind:

• Do not rely on blood tests: It is incredibly important to stick to the exact daily dose recommended by your doctor, and to avoid taking more. Blood tests to check Vitamin A levels are unreliable while on these medications. Because you are missing the transport protein, your blood levels of Vitamin A will always appear artificially low on lab tests, even if your body’s tissues have plenty.
• Avoid overdosing: Trying to raise your blood levels by taking higher doses of Vitamin A can lead to toxic and dangerous overdoses. Always follow your medical team’s specific dosing instructions and report any vision symptoms rather than relying on blood work.
• Take with food: Vitamin A is a “fat-soluble” vitamin. This means it requires dietary fat to be absorbed properly by your body. You should take your supplement with a meal or snack that contains some fat.
• Check your multivitamins: Because Vitamin A is stored in the body, taking too much can cause harm, particularly if you are pregnant or planning to become pregnant. Check the labels of any daily multivitamins you take, as they often contain additional Vitamin A, and discuss the total amount with your doctor.