Health

New UK Study Reveals Alarming Connection Between Low Transthyretin Levels and Major Health Risks

2025-05-19

Author: Ming

A Shocking Discovery in the UK Biobank Data

A groundbreaking analysis of the vast UK Biobank database has revealed a troubling link between low levels of transthyretin (TTR) and a heightened risk of severe and potentially fatal diseases, including Alzheimer's disease (AD) and stroke. This extensive study involved data from nearly half a million participants, shedding light on a crucial health marker.

What They Found

Among the examined subjects, 234 were diagnosed with transthyretin amyloidosis (ATTR), a progressive illness marked by the destabilization of TTR and the harmful deposition of amyloid proteins. The findings illustrated that individuals with ATTR had significantly lower TTR and APOA1 levels, while showing alarming increases in comorbid conditions such as AD, dementia, rheumatoid arthritis, chronic obstructive pulmonary disease, and many others (all P < .05).

Deeper Implications of Low TTR Levels

In a subset of 24,296 unrelated Caucasian participants, similar associations were found. Lower TTR levels correlated strongly with a higher incidence of AD, osteoporosis, and chronic obstructive pulmonary disease (all P < .05). A Mendelian randomization analysis indicated that reduced TTR may actually precede and worsen the risk of various diseases, including chronic kidney disease and cataracts. Researchers are alarmed at this potential causality.

Presenting the Findings to the World

The striking results were recently shared at the 2025 Peripheral Nerve Society Annual Meeting in Edinburgh, Scotland, by Dr. Sami Khella, chief of neurology at Penn Presbyterian Medical Center. His presentation emphasized the long-standing belief in the protective importance of TTR against serious diseases.

Prior Studies Reinforce the Concerns

Further linked to this topic, an earlier analysis highlighted in Nature Communications indicated that decreasing TTR levels are also significantly tied to increased heart failure and mortality rates. This consistent theme underscores the urgent need to understand TTR stabilizers and their potential therapeutic benefits further.

The Genetics Behind TTR Levels

Past studies have shown that various factors influence TTR levels, including sex and inflammation. Notably, carriers of the pathogenic V142I TTR variant exhibit markedly lower TTR levels compared to non-carriers, raising crucial questions about genetic predispositions and their ramifications. Specifically, each standard deviation decrease in TTR was found to correlate with a 17% greater risk of heart failure and an 18% increased risk of overall mortality.

What Next?

With the clarity brought by these findings, researchers are calling for more investigations into the impact of TTR stabilization therapies on these diseases, especially given their potential role in disease prevention and progression. As the conversation around TTR continues to grow, the health implications remain profoundly significant.