L-Threonine for ALS: No Proven Benefits

observational-study PMID: 18425887

L-Threonine for ALS: No Proven Benefits

Quick Summary: A major review of clinical trials looked at whether L-threonine, an amino acid supplement, could help people with amyotrophic lateral sclerosis (ALS), also called motor neuron disease (MND). The research found no evidence that L-threonine improves survival, muscle strength, or daily function. It also checked branched-chain amino acids (like leucine, valine, and isoleucine) and got similar results—safe but not effective.

What the Research Found

This systematic review combined data from multiple trials to test amino acid treatments for ALS, a tough disease that weakens muscles and shortens life. Researchers hoped these supplements might slow things down, but the results were clear: no real benefits.

Survival rates stayed the same: People taking L-threonine lived about as long as those on placebo (fake treatment). The hazard ratio—a math way to measure risk—was 1.09, meaning no difference.
Muscle strength didn't improve: Tests like grip strength or leg lifts showed no gains from L-threonine or the other amino acids.
Daily function unchanged: Scales that rate eating, walking, or breathing (like the ALS Functional Rating Scale) didn't get better.
Quality of life not studied: The trials skipped checking how patients felt overall, like mood or comfort.
Side effects were mild: Both L-threonine and controls caused similar issues, like stomach upset, in about 12-15% of people—nothing serious.

In short, these amino acids didn't slow ALS progression or extend life.

Study Details

This was a big 2008 review by Cochrane experts, pulling together six solid trials on ALS patients. They searched medical databases up to 2003 and even asked study authors for more info. Two trials got dropped due to weak methods, leaving four for the main analysis.

Who was studied: Adults diagnosed with ALS/MND, a group of 40-100 people per trial, all with the disease's classic symptoms like muscle weakness and nerve damage.
How long: Most trials lasted 6-12 months, tracking survival and function over that time—enough to spot short-term changes but not super long-term ones.
What they took: L-threonine at 4 grams per day, taken by mouth (often mixed in drinks or food). Branched-chain amino acids were 10-60 grams daily. Controls got placebo pills or usual care.

Stats came from tools like the Parmar method for survival odds and Review Manager software for other results.

What This Means For You

If you or a loved one has ALS, this study says don't count on L-threonine supplements to fight the disease. It's not a miracle fix for survival or strength—stick to doctor-recommended treatments like riluzole, which has some proven benefits. Amino acids seem safe for short use, so if you're already taking them for other reasons (like diet), they're unlikely to hurt, but they won't help ALS. Talk to your doctor before starting any supplement; focus on proven care, therapy, and support to manage symptoms. More research is needed for better options.

Study Limitations

This review isn't perfect, and it was later withdrawn from PubMed (reason unclear, so take it with caution). Here's what to watch:

Varied setups: Trials used different doses and groups, making it hard to compare perfectly.
Small groups and short time: With only dozens per study and under a year of follow-up, they might miss subtle or long-term effects.
Missing data: Seven other trials were skipped due to incomplete info or too-short runs, which could bias results.
No full picture: Skipped quality-of-life checks, and negative findings might not get published as much.
Old data: Based on searches up to 2003, so newer ALS treatments aren't included.

Overall, while reliable at the time, wait for fresh studies before banking on L-threonine for ALS.

Key Findings

The study found no statistically significant evidence that L-threonine or branched-chain amino acids (BCAAs: L-leucine, L-valine, L-isoleucine) improve survival, muscle strength, or physical function in amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Pooled hazard ratios for survival did not favor either treatment, and secondary outcomes like functional rating scales and adverse events were comparable to control groups. Quality of life was not assessed.

Study Design

This 2008 systematic review and meta-analysis analyzed six randomized or quasi-randomized trials involving ALS/MND patients. Studies varied in sample size (total unspecified) and duration, with some excluded for inadequate follow-up. Methodological quality was assessed, and missing data were requested from authors. Survival analysis used the Parmar method; other outcomes were analyzed via Review Manager 4.2.

Dosage & Administration

Doses of BCAAs ranged from 10–60 g/day, while L-threonine was administered at 4 g/day. Amino acids were delivered orally, often mixed with food or beverages. Control groups received placebo or standard care.

Results & Efficacy

Survival: Pooled hazard ratios (HR) indicated no benefit. For example, one BCAA trial reported HR 1.01 (95% CI 0.79–1.29; p = 0.93), and an L-threonine trial showed HR 1.09 (95% CI 0.84–1.42; p = 0.52), both non-significant.
Muscle Strength/Function: No improvements were observed in validated scales (e.g., ALS Functional Rating Scale) or strength measurements.
Adverse Events: Both treatments were well-tolerated, with adverse event rates similar to controls (e.g., 15% vs. 12% in one BCAA trial; p > 0.05).

Limitations

Heterogeneity: Variability in study designs, dosages, and populations limited comparability.
Incomplete Data: Seven trials were excluded due to missing data or short duration, potentially introducing selection bias.
Small Sample Sizes: Individual trials had limited statistical power (e.g., n = 40–100 per group).
Lack of Long-Term Data: Most studies had follow-up periods under 12 months, insufficient to assess ALS progression.
No Quality-of-Life Assessment: Critical patient-reported outcomes were absent.
Publication Bias: Negative results may be underreported in the literature.

Clinical Relevance

ALS/MND patients should not expect L-threonine or BCAAs to prolong survival or slow disease progression based on current evidence. While these supplements appear safe, their lack of efficacy in rigorous trials suggests prioritization of proven therapies (e.g., riluzole). For supplement users, this study underscores the importance of evidence-based interventions and highlights the need for further research into amino acid therapies with standardized dosing and longer follow-up. Clinicians should advise against relying on L-threonine or BCAAs as standalone treatments for ALS/MND.

Note: The study was later withdrawn by PubMed, though the reason is unspecified. This may affect its reliability, warranting cautious interpretation.