Japanese study reveals arginine can reduce Alzheimer’s disease markers

Japanese researchers from Kindai University have found that oral arginine, a naturally occurring amino acid, may significantly reduce a precursor to Alzheimer’s disease. In their experiment involving mice and fruit flies, arginine lowered amyloid β (Aβ) plaque formation in vitro and in vivo. 

Arginine supplementation also supported broader neuroprotective and anti-inflammatory effects.

“What makes this finding exciting is that arginine is already known to be clinically safe and inexpensive, making it a highly promising candidate for repositioning as a therapeutic option for AD,” explains project lead, professor Yoshitaka Nagai, department of Neurology, Kindai University Faculty of Medicine.

“Our findings open up new possibilities for developing arginine-based strategies for neurodegenerative diseases caused by protein misfolding and aggregation,” he notes. “Given its excellent safety profile and low cost, arginine could be rapidly translated to clinical trials for Alzheimer’s and potentially other related disorders.”

The researchers note that while arginine is sold as a dietary supplement, the dose and routine used in their study were designed for research and do not match those of commercial products. 

However, they believe their findings point to a cost-effective, readily available strategy that may one day support Alzheimer’s patients globally.

Supplementing for prevention

Current treatments cannot cure Alzheimer’s disease. It is a progressive disorder that damages nerve cells in the brain and is one of the main causes of dementia around the world.

While antibody-based drugs targeting amyloid β have recently become available, the researchers note their benefits have been modest. These therapies can also be expensive and may cause immune-related side effects, emphasizing the need for safer, low-cost options that are more accessible.

The new paper published in Neurochemistry International tested oral arginine in two widely used Alzheimer’s disease models: a Drosophila (fruit fly) model, expressing Aβ42 with the Arctic mutation (E22G); and a mouse model, carrying three familial Alzheimer’s disease mutations.

In both cases, arginine treatment led to a significant drop in Aβ buildup and reduced the harmful effects associated with Aβ exposure, according to the paper.

Mice receiving arginine also performed better in behavioral assessments and showed decreased expression of pro-inflammatory cytokine genes linked to neuroinflammation, a key contributor to Alzheimer’s disease progression. 

Arginine is already approved for clinical use in Japan and shows good brain permeability, which means the amino acid may bypass multiple early hurdles that often slow traditional drug development, note the scientists.

They stress that additional preclinical and clinical studies are needed to confirm if these effects will translate to humans and to determine appropriate dosing strategies.

“Even so, the results present strong proof of concept that basic nutritional or pharmacological supplementation could reduce amyloid pathology and improve neurological health,” they conclude.

Tackling Alzheimer’s through diet

In other Alzheimer’s dietary research, a UK study found that omega-3 fatty acids may help protect women against Alzheimer’s disease, potentially more than men. It uncovered a noticeable loss of unsaturated fats, such as those containing omega fatty acids, in the blood of women with the disease.

Another recent paper revealed that people with the highest genetic risk for Alzheimer’s disease tend to benefit more from following a Mediterranean-style diet, having a greater reduction in related dementia risk compared to those at lower genetic risk.