This podcast is part of our October 2023 Cognition and Mental Health special issue. Download the full issue here.
Reference
Ostfeld I, Ben-Zeev T, Zamir A, et al. Role of β-alanine supplementation on cognitive function, mood, and physical function in older adults; double-blind randomized controlled study. Nutrients. 2023;15(4):923.
Study Objective
To determine if supplementation with beta-alanine (β-alanine) affects cognition, mood, or physical function in an elderly population
Key Takeaway
β-alanine did not improve physical function in older adults compared to placebo; however, it may have had some benefit for depression and cognitive dysfunction, especially in those with borderline or below-normal cognitive function at baseline.
Design
Randomized, placebo-controlled study
Participants
Original recruitment garnered 100 volunteers from various clinics across Israel (aged 60–80 years; 15 men and 35 women in the β-alanine group and 14 men and 36 women in the placebo). Twenty-one participants dropped out, leaving 79 participants for final analysis (38 in the intervention group; 41 in the placebo group).
Exclusion criteria included any supplementation with β-alanine in the 6 months prior to the study and any neurological condition (eg, dementia, movement disorders).
Intervention
Participants took 2.4 g of slow-release β-alanine orally in 2 600-mg tablets twice daily for 10 weeks. The placebo was identical and contained hydroxypropyl methylcellulose in lieu of β-alanine. Natural Alternatives International (Carlsbad, California) provided the tablets and placebo.
Investigators made all assessments at 3 separate time points:
- PRE-test
- MID-test (week 5)
- POST-test (week 10)
Study Parameters Assessed
- Montreal Cognitive Assessment (MoCA) detects mild cognitive impairment in adults.
- Stroop test, which measures cognitive and executive function
- Profile of Mood States (POMS), measuring tension, depression, anger, vigor, fatigue, and confusion
- Geriatric Depression Scale (GDS)
- Geriatric Anxiety Scale (GAS)
- Hand-grip dynameter
- Sit-to-stand test
Primary Outcome
Do 10 weeks of slow-release β-alanine supplementation affect cognitive function and improve executive function in older adults?
Key Findings
MoCA: Both groups improved MoCA (F=5.4, P=0.005). Pre to post hoc analysis revealed MoCA scores were significantly greater for β-alanine (BA) than for placebo (PL) at both MID (P=0.009) and POST (P=0.016) time points. When MoCA scores were examined in participants with borderline or below-normal MoCA scores (ie, ≤26), a significant interaction was found (F=3.37, P=0.042).
Stroop: All groups improved in time (F=8.83, P<0.001). Reaction times also improved from PRE to MID (P=0.027) and from PRE to POST (P<0.001).
However, no significant interactions between BA and PL were noted for reaction time (F=0.343, P=0.711). Both groups improved in speed accuracy (F=15.1, P<0.0001).
Behavioral measures: There were no differences between groups in tension (P=0.571), depression (P=0.559), anger/hostility (P=0.103), vigor (P=0.101), fatigue (P=0.164), or confusion (P=0.131). In addition, no differences between BA and PL were noted in total mood score.
There was a significant group difference in Geriatric Depression Scale (P=0.037) but only a trend toward a difference in Geriatric Anxiety Scale (P=0.096). Post hoc analysis for Geriatric Depression Scale indicated that the mean rank for depression scores was significantly lower at MID (P=0.012) and POST (P=0.002) compared to PRE in the BA group. No significant differences from PRE were noted in the PL group.
There were no differences noted between groups for total mood score (P=0.131).
Hand/grip strength: Analysis of changes in hand grip strength revealed a trend toward an improvement with both groups combined (F=2.933, P=0.66) but no significant interaction (F=0.258, P=0.773).
Sit to stand: Examination of performance in the sit-to-stand test revealed a significant main effect for time (F=22.1, P<0.001) with both groups combined but no significant interaction (F=0.320, P=0.727). Improvements were observed from PRE to MID (P<0.001) and from MID to POST (P=0.005). Although no significant main effect was noted for peak power during the sit-to-stand assessment (F=1.103, P=0.335), a trend for an interaction was observed (F=2.554, P=0.093). No main effects for time or interactions were observed in mean power output (F=1.46, P=0.235 and F=1.312, P=0.272, respectively) or fatigue rate (F=0.326, P=0.723 and F=1.081, P=0.342, respectively) during the 5 sit-to-stand repetitions.
Transparency
This research was funded by Natural Alternative Inc (Carlsbad, CA, USA), a manufacturer of the supplement used in the study. However, the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Practice Implications & Limitations
Strength loss, cognition changes, and mood changes are all concerns of aging. These aging processes can be exacerbated if individuals are inactive as they age. More rapid progression of these symptoms can be caused by sarcopenia (muscle loss)1,2 and/or brain-function loss secondary to oxidative stress and brain atrophy.3
It seems reasonable to consider β-alanine as a supplement to address these concerns in aging populations.
β-alanine is a nonessential amino acid naturally present in the body. It combines with L-histidine to form the dipeptide beta-alanyl-L-histidine, aka carnosine. This reaction is catalyzed by carnosine synthase. L-histidine is an essential amino acid present in the serum only after consumption.4 Carnosine accumulates in its highest concentrations in the skeletal muscle.5
Many trials have investigated the effects of β-alanine supplementation on muscle carnosine content and exercise performance.6 In one study, oral BA supplementation increased muscle carnosine content and improved anaerobic exercise performance in rowers. Improved performance was attributed to the buffering capacity of carnosine, which helps to reduce the accumulation of lactic acid during high-intensity exercise.5
A meta-analysis by Hobson et al further supported the positive effects of BA supplementation on exercise performance. The analysis included multiple studies and found that β-alanine supplementation improved exercise lasting 60 to 240 seconds and exercise lasting more than 240 seconds but did not provide benefits for exercise lasting less than 60 seconds.6
It is most helpful to create a concerted exercise program alongside the supplementation of β-alanine rather than provide the dietary supplement alone.
Further, BA has been studied for its enhancement of combat-specific performance in military subjects, showing benefits in 50-meter casualty carry time and cognitive performance.7
The Ostfeld et al study under review here was helpful in addressing 2 commonly overlapping scenarios in aging populations: strength decline and cognitive changes.8 Cognitive decline, when progressive, is a major cause of morbidity in aging populations.9 Sarcopenia can also be a significant cause of morbidity, especially in aging orthopedic patients.10
It is most helpful to create a concerted exercise program alongside the supplementation of β-alanine rather than provide the dietary supplement alone. It is possible that the study end points (in particular, strength) may reflect improvements not seen in the current study design.
While the addition of exercise may improve results, it is important to note that studies have shown that BA supplementation can improve exercise performance in inactive 60- to 80-year-olds.11
Of note, 21 patients dropped out of the study, but the paper gives only an annotation saying that “participants were no longer interested in participating.” Precisely why they dropped out was not mentioned. This implies inconvenience of the intervention at the very least. Paresthesia (tingling of the skin) and temporarily increased alanine aminotransferase (ALT) have been described in the medical literature as possible side effects. There was no indication of these or any other untoward effects in this study.
Finally, it would be interesting to see if a higher dosage might have been more effective. Doses as high as 6.4 g/day have been used for 24 weeks safely.12 Future studies may also look at increased dosing, as many studies have used 4.8 g/day of BA for physical performance enhancement.5 Perhaps this is needed in older populations due to generally poorer absorption with advanced age.
