A recent study exploring the effects of antioxidants on Alzheimer’s disease (AD) has yielded unexpected results, raising concerns about the use of a specific vitamin combination. Researchers found that while a combination of vitamin E, vitamin C, and alpha-lipoic acid (ALA) appeared to reduce oxidative stress in the brain, it was also associated with accelerated cognitive decline in patients with mild to moderate AD.
The 16-week, double-blind, randomized study, published in Archives of Neurology, investigated the impact of this antioxidant combination, as well as high-dose coenzyme Q (CoQ), on cerebrospinal fluid (CSF) biomarkers related to AD pathology. Seventy-eight participants were divided into three groups: one receiving the vitamin E, C, and ALA combination (E/C/ALA); one receiving CoQ; and a placebo group.
While the E/C/ALA combination did lead to a reduction in CSF F2-isoprostane levels, a marker of oxidative stress, it also resulted in a more rapid decline in cognitive function as measured by the Mini-Mental State Examination (MMSE). This unexpected finding contrasted with the lack of any significant change in CSF biomarkers related to amyloid and tau, the hallmark proteins of AD. CoQ, on the other hand, showed no beneficial effects on CSF biomarkers whatsoever.
“It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD,”1 the authors caution. The more concerning finding, they add, is the accelerated cognitive decline observed in the E/C/ALA group, which “raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered.”2
Experts in the field have weighed in on the study’s implications. Dr. Nikolaos Scarmeas, of Columbia University Medical Center, described the study as “extremely useful,” despite its negative results. He emphasized the complexity of AD and the importance of considering multiple biomarkers and mechanisms alongside clinical outcomes. The disconnect between the apparent reduction in oxidative stress and the observed cognitive decline highlights this complexity, suggesting that the mechanisms underlying cognitive decline in AD are not fully understood.
The study’s authors suggest that the accelerated cognitive decline in the E/C/ALA group may not be directly related to AD pathology, as it wasn’t reflected in changes in amyloid or tau CSF biomarkers. However, they stress the need for careful monitoring of cognitive function in any future studies involving this antioxidant combination. The lack of benefit observed with CoQ also suggests that further investigation of this compound in AD is unlikely to be fruitful.
This study serves as a reminder that while antioxidants hold promise for various health conditions, their effects in complex diseases like Alzheimer’s are not always predictable. Further research is crucial to fully understand the role of oxidative stress and the potential benefits and risks of antioxidant therapies in AD.
2 Responses
The fact that the cognitive decline in the E/C/ALA group wasn’t accompanied by changes in amyloid or tau biomarkers is intriguing. It suggests that this particular antioxidant cocktail might be impacting cognitive function through a pathway independent of the classic AD pathology. This warrants further investigation to understand what’s happening at a mechanistic level and whether there are specific subgroups of patients who might be more vulnerable to this effect.
This study highlights the crucial need for rigorous, double-blind, randomized trials even for seemingly innocuous supplements. The unexpected negative outcome with the vitamin E, C, and ALA combination underscores how complex Alzheimer’s disease is and that reducing oxidative stress doesn’t necessarily translate to improved cognitive function. It’s a reminder that we need to be cautious about extrapolating from presumed mechanisms to clinical benefits.