Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare form of heart failure caused by the misfolding of the transthyretin (TTR) protein, which normally functions as a transport vehicle for vitamin A in the bloodstream. This protein accumulation stiffens the heart muscle, impairing its ability to pump blood effectively. Because certain ATTR-CM treatments—specifically TTR-silencing medications—work by reducing the liver’s production of TTR, patients often face a secondary risk of vitamin A deficiency, requiring clinical monitoring and, in many cases, daily supplementation.
How TTR-Silencing Medications Impact Vitamin A
Vitamin A (retinol) does not travel through the blood independently; it must bind to a transport molecule. "Vitamin A (retinol) does not circulate freely in the blood," explains Julia Zumpano, RD, a specialist in metabolic and clinical nutrition at the Cleveland Clinic. "Instead, retinol binds to a carrier protein called retinol-binding protein (RBP), and this combination then connects to TTR, which facilitates the body’s use of vitamin A."
When patients are treated with TTR-silencing medications, the overall concentration of TTR in the body drops. This reduction is intentional to slow the progression of amyloidosis, but it creates a functional deficit in vitamin A transport. Drugs categorized as TTR silencers include:
- Patisiran (Onpattro)
- Inotersen (Tegsedi)
- Vutrisiran (Amvuttra)
According to Dr. Albert Hicks, medical director of cardiac transplantation at the University of Maryland School of Medicine, these silencers can cause a functional vitamin A deficiency because they deplete the primary transporter protein required for the vitamin to reach target tissues.
Identifying Signs of Vitamin A Deficiency
Because vitamin A is essential for immune function, reproductive health, and vision, a deficiency can lead to systemic symptoms. Patients undergoing TTR-silencing therapy should monitor for:
- Night blindness: Difficulty seeing in low-light environments due to a lack of rhodopsin, a protein in the eye that requires vitamin A.
- Dermatological changes: Thick, rough skin patches, particularly on the elbows, knees, or buttocks.
- Increased infection risk: More frequent occurrences of respiratory, gastrointestinal, or urinary tract infections.
- Ocular symptoms: Spots or abnormal wrinkling on the whites of the eyes.
Laboratory blood tests for vitamin A can be misleading in patients on these medications. As Zumpano notes, the medication fundamentally alters how vitamin A is transported, making standard lab values difficult to interpret compared to the general population. Providers typically rely on a combination of clinical symptoms and consistent monitoring rather than just blood test results.
Safe Supplementation Guidelines
For patients prescribed TTR-silencing drugs, clinical experts often recommend a daily vitamin A supplement to maintain healthy levels. Dr. Jacqueline Dowe, a cardiologist at the Orlando Health Heart and Vascular Institute, advises that patients should generally begin supplementation at the same time they start their TTR-silencing medication to preemptively avoid a deficiency. A common clinical recommendation is 3,000 international units (IU) of vitamin A daily.
However, excess vitamin A is toxic. Dr. Dowe warns that high levels can lead to severe headaches, vertigo, blurred vision, nausea, muscle aches, and loss of coordination. Because the U.S. Food and Drug Administration (FDA) does not regulate the safety or efficacy of over-the-counter supplements, patients should prioritize products with third-party testing certifications, such as USP, NSF, or ConsumerLab labels.
Questions to Discuss With Your Healthcare Team
Managing nutritional intake alongside complex cardiac therapy requires clear communication with a medical provider. Patients may consider asking the following:
- What is the specific frequency for monitoring my vitamin A levels?
- Are there specific dietary sources, such as beef liver, sweet potatoes, or spinach, that I should emphasize in my meal planning?
- Can you provide a recommendation for a specific, third-party tested supplement brand?
- Which symptoms of either deficiency or toxicity should prompt an immediate call to your office?
Consistency is critical. Dr. Tadeo Diaz Balderrama, a cardiologist at SSM Health, emphasizes that while the time of day is less important than the regularity of the dose, patients must remain consistent with their supplementation regimen to ensure their body has the necessary building blocks for organ health and vision stability.