Exercise is often described as the best medicine, yet for many older adults it can be a difficult prescription to follow. Age-related physical and cognitive challenges often make it hard to sustain regular activity.

A study published in Dietetics (August 2025) by researchers at UT Health San Antonio the clinical enterprise of The University of Texas at San Antonio examined whether combining exercise with branched-chain amino acid (BCAA) supplementation could improve outcomes in older adults. In a small, randomized, double-blind, placebo-controlled trial, they found that BCAAs enhanced performance, lowered fatigue, and eased symptoms of depression in many participants.

Inflammation and amino acids

“For years, we’ve been investigating how inflammation drives functional decline with aging and disease,” said study co-author Jason O’Connor, PhD, associate professor of pharmacology with a joint appointment at the Veterans Administration’s Geriatric Research Education and Clinical Center. “Among the many factors, amino acid metabolism appears to play a key role.”

His work focuses on how inflammation impairs the central nervous system. BCAAs leucine, isoleucine, and valine are not only building blocks for protein and muscle but also seem to influence inflammation and brain health.

“During inflammation, amino acid metabolism changes in ways that ripple through other biological systems. We want to better understand the brain’s role in fatigue compared with physical contributors,” O’Connor explained.

The complexity of fatigue

Fatigue is not just tiredness; it is a multifaceted, often debilitating condition. It can arise from muscle weakness (motor fatigue) or from the brain (central fatigue), where perception of exhaustion originates. Central fatigue, influenced by poor sleep, cardiovascular disease, or chronic inflammation, is not well understood. While exercise is a proven strategy against fatigue, many older adults struggle to keep up, especially when other health issues are present.

“Fatigue can spiral,” O’Connor said. “Someone may be capable of cleaning out the garage, but if they feel drained or unmotivated, they avoid it. Then guilt sets in, they ask for help, and feel guilty again. This cycle is hard to break. What if we could interrupt it and give people a way to reclaim quality of life?”

Short- and long-term benefits

BCAAs may provide benefits on multiple levels. In the short term, they appear to support brain pathways linked to reduced mental fatigue and improved mood, while also limiting muscle breakdown. Over the long term, they activate muscle-building processes such as the mTOR signaling pathway, helping preserve strength.

Why focus on older adults?

Past research on BCAAs in younger populations has shown mixed results. O’Connor emphasized the importance of testing them in older adults, who are more susceptible to both physical and mental fatigue.

“Our earlier studies suggest that aging and inflammation disrupt amino acid balance in the brain. Low levels of these amino acids are often tied to fatigue, particularly central fatigue,” O’Connor said. “We wanted to see if supplementation could restore balance and reduce this burden, while also amplifying the benefits of exercise.”

Study design

The pilot study, supported by the San Antonio Claude D. Pepper Older Americans Independence Center, enrolled 20 men and women with obesity, averaging 70 years old. Participants completed eight weeks of moderate aerobic and strength training. One group drank a placebo beverage, while the other consumed a BCAA drink (2:1:1 ratio, with leucine emphasized).

“These amino acids are more than protein precursors,” O’Connor noted. “Leucine directly affects skeletal muscle and interacts with other amino acids in the brain that may influence mental fatigue.”

Results

After eight weeks, the outcomes were striking.

“We expected exercise alone to improve outcomes, with supplementation offering an extra boost. Instead, exercise by itself showed only modest effects,” O’Connor said. “This may help explain why many people struggle to stick with exercise if they don’t feel benefits quickly, motivation fades.”

The placebo group experienced minimal gains in strength and endurance, along with a 5% rise in fatigue and worsening depression scores. By contrast, the BCAA group showed modest improvements in strength and endurance, a 45% reduction in fatigue, and a 29% drop in depressive symptoms.

Source: https://news.uthscsa.edu/pilot-study-branched-chain-amino-acids-may-help-physical-mental-fatigue-in-older-adults/