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A new study suggests that an oral medication, sodium benzoate, may reduce the levels of disease-related proteins in the blood of patients with mild Alzheimer’s disease. The research also indicates that patients who had higher initial levels of a specific protein, called amyloid-beta 1–42, experienced greater cognitive benefits from the treatment. These findings, published in the journal Translational Psychiatry, point toward a potentially safe and convenient therapeutic option for individuals with Alzheimer’s disease.
Alzheimer’s disease is a progressive brain disorder that gradually diminishes memory and other important mental functions. For decades, a leading theory has suggested that the buildup of proteins called amyloid-beta peptides in the brain is a primary cause of the nerve cell damage and cognitive decline seen in the disease. This idea has gained support with the recent approval of new treatments that directly target and remove these amyloid-beta proteins.
These therapies, which are administered through intravenous infusions, have shown an ability to slow cognitive decline. However, they can be associated with side effects, including brain swelling or bleeding, and they present logistical challenges for patients and healthcare systems due to their high cost and the need for regular hospital visits for infusions and monitoring.
This situation has prompted a search for safer and more accessible treatments that can also address the amyloid-beta buildup. One candidate is sodium benzoate, a compound that is a metabolite of cinnamon and is widely used as a food preservative. It is also approved as a treatment for certain metabolic disorders.
Previous research provided early hints of its potential. Studies in animal models of Alzheimer’s disease showed that oral sodium benzoate could reduce the amyloid protein load in the brain and improve learning and memory. Clinical trials in humans subsequently found that daily doses of 750 milligrams or 1000 milligrams improved cognitive function in patients with mild Alzheimer’s disease, with a safety profile comparable to a placebo.
The current investigation was designed as a secondary analysis of a previous trial to explore two key questions: can oral sodium benzoate lower the levels of amyloid-beta peptides in the blood of people with Alzheimer’s, and is there a connection between a patient’s initial amyloid-beta levels and their cognitive response to the treatment?
To answer these questions, Chieh-Hsin Lin of Chang Gung University and Hsien-Yuan Lane of China Medical University Hospital in Taichung City analyzed data from a previously conducted clinical trial. The original study was a 24-week, randomized, double-blind, placebo-controlled trial involving 149 patients from three medical centers in Taiwan. The double-blind design means that neither the participants nor the investigators knew who was receiving the active treatment versus an inactive placebo, which helps prevent bias in the results.
Participants were individuals between 50 and 100 years old who had been diagnosed with probable mild Alzheimer’s disease. They were generally in good physical health and had cognitive scores within a specific range that indicated a mild stage of the disease. The patients were randomly assigned to one of four groups for the 24-week period. One group received a placebo, while the other three groups received different daily doses of sodium benzoate: 500 milligrams, 750 milligrams, or 1000 milligrams.
Throughout the study, researchers assessed the cognitive function of each participant using a standard test called the Alzheimer’s Disease Assessment Scale-cognitive subscale. This is a common tool used in clinical trials for Alzheimer’s disease, and on this scale, a lower score indicates better cognitive performance. Before the trial began and after it concluded at 24 weeks, blood samples were collected from the participants.
The research team used these samples to measure the plasma concentrations of two specific amyloid-beta peptides: amyloid-beta 1–40 and amyloid-beta 1–42. The analysis focused on whether the levels of these proteins changed after treatment and if these changes related to cognitive outcomes. The study combined the data from the two higher dose groups, 750 and 1000 milligrams per day, as these were the dosages that showed cognitive benefits in the original trial.
The analysis revealed that sodium benzoate had a noticeable effect on amyloid-beta levels. When combining the data from the two effective dose groups, the treatment led to a significant reduction in the levels of amyloid-beta 1–40 in the blood compared to the placebo group. A similar significant reduction was seen in the total amount of amyloid-beta, which is the sum of both the 1–40 and 1–42 peptides. While there was a trend toward lower amyloid-beta 1–42 levels in the treatment group, this change was not statistically significant on its own. The 500-milligram dose did not produce significant changes in amyloid levels when analyzed separately.
The study also uncovered a predictive relationship between initial amyloid-beta levels and the treatment’s cognitive benefits. Among patients receiving the effective doses of 750 or 1000 milligrams of sodium benzoate, those who started the trial with higher levels of amyloid-beta 1–42 in their blood showed greater cognitive improvement over the 24 weeks. This improvement was measured as a larger decrease in their cognitive assessment scores.
This connection between higher baseline amyloid-beta 1–42 and better cognitive outcomes was not observed in the group that received the placebo, suggesting the effect was specific to the sodium benzoate treatment. The study also looked at other biological markers related to antioxidants but found no correlation between them and the changes in amyloid-beta levels.
The researchers identified some limitations to their work that suggest areas for future inquiry. The sample size was moderate, which might mean that some real but smaller effects were too subtle to be detected with statistical confidence. The 24-week duration of the trial is also relatively short, so it is unknown if the cognitive and biological benefits would persist or grow over a longer period.
Additionally, the participants were of Han Taiwanese descent, and more studies would be needed to confirm if the results apply to people of other ethnic backgrounds. Future research could also explore if different dosages, perhaps even higher ones, might produce different or stronger effects. A significant question that remains is how changes in amyloid-beta levels in the blood relate to the amount of these proteins in the brain and cerebrospinal fluid, where they are thought to cause the most damage.
Future studies could incorporate brain imaging techniques to directly observe the treatment’s impact on the brain, providing a more complete picture of its mechanism. Despite these limitations, the findings suggest that sodium benzoate, an oral medication with an excellent safety record, has the potential to become a new therapy for Alzheimer’s disease that works by reducing amyloid-beta proteins.
The study, “Sodium benzoate treatment decreased amyloid beta peptides and improved cognitive function among patients with Alzheimer’s disease: secondary analysis of a randomized clinical trial,” was authored by Chieh-Hsin Lin and Hsien-Yuan Lane.
