Key findings from detailed records
An eight-week trial in 70 adults with regular fatigue reported time-by-group differences in overall fatigue, work-related fatigue and anger–hostility. The intervention combined 5-ALA with iron; the control also contained iron. These are subjective outcomes under the studied conditions. PMID 32994490
KNOWLEDGE RECORD
- Category
- Metabolism and cellular function
- Last Reviewed
Names and related search terms5-ALA / 5-Aminolevulinic acid / 5-Aminolevulinic acid
Study type: selected human intervention studies.
OUTCOME-SPECIFIC EVIDENCE
Scientific Evidence Profile
Assessment pending
An outcome-specific assessment has not yet been completed. This is not a finding that the ingredient is ineffective. The study records below remain available.
This profile concerns the stated outcome and population, not the ingredient as a whole. It is not a probability of benefit, a safety rating, a product efficacy rating or an indication of product adoption.
How we assess evidenceIngredient Profile
- What is it?
- 5-ALA is 5-aminolevulinic acid, a precursor in porphyrin synthesis. The molecule's identity is separate from the route, formulation and purpose of its use. [1]
Sources for this profile
Compound properties and formulation properties are different. These sources do not establish the efficacy of a finished supplement.
- PubChem — 5-Aminolevulinic Acid (CID 137) Chemical identity reference. Maintained by NCBI, U.S. National Library of Medicine. Database record; not a clinical trial.
Profile sources checked:
Read the evidence in context
- Evidence: what was measured in the stated population or experimental model.
- Inference: an interpretation connecting findings; its applicability depends on the study conditions.
- Hypothesis: a proposed explanation or effect that remains to be tested.
Why It Matters #
How does the focus on heme relate to human trials combining 5-ALA with iron? Check the detailed records for study conditions and use the literature map to compare other populations and outcomes.
What Was Studied #
70 people aged 20–64 who regularly experienced physical fatigue
Randomized, double-blind, placebo-controlled parallel-group trial · 8 weeks PMID 32994490
What Was Found #
Overall fatigue, work-related fatigue and anger–hostility decreased, with significant time-by-group interactions (p=0.040, 0.020 and 0.045). Other mood improvements were within-group comparisons. PMID 32994490
What the Evidence Means #
A short-term trial using subjective measures. Iron was also included in the control group. PMID 32994490
What We Can Learn #
In the fatigue trial, both groups received the same iron co-intervention, making the added 5-ALA the key treatment difference. Other trials used different 5-ALA/iron combinations; their doses and outcomes should be read separately.
What Remains Unknown #
Further questions include reproducibility across populations and formulations, and the long-term balance of benefits and harms. Use the literature map as a starting point for these questions.
LITERATURE MAP / 10 PAPERS
Compare papers by conditions and findings.
A literature map comparing human studies of blood glucose, fatigue, exercise and tolerability. Key distinctions include iron co-administration, salt-based dose reporting and participants with disease.
Selected: 2026-09-21. Bibliographic information checked against Europe PMC / PubMed. Editorial selection considered major papers and a range of populations and questions. This is not a systematic search covering all recent research.
11 RECORDS
A dash marks fields outside the bibliographic record. Use detailed records to compare findings and design records to connect mechanisms.
| Paper and topic | Study conditions | Findings and scope |
|---|---|---|
| Mechanism and designEffects of 5-aminolevulinic acid and sodium ferrous citrate on fibroblasts from individuals with mitochondrial diseasesPMID 31332208 # | Study conditions Human-derived cells / Heme and the respiratory chain — | Findings and scope ALA combined with sodium ferrous citrate was examined in fibroblasts from patients with mitochondrial disease and controls. The study assessed oxidative phosphorylation components, oxygen consumption and ATP. Distinguish 5-ALA from its salt forms and identify any iron co-intervention. Evidence from a combination cannot isolate the contribution of one ingredient. |
| Iron co-administration / Blood glucose5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects.PMID 23759263 # | Study conditions Randomized, double-blind, placebo-controlled trial
| Findings and scope The 15 mg ALA-P + 1.8 mg iron arm reduced fasting glucose by 2.32 mg/dL and 2-hour glucose by 14.2 mg/dL more than placebo; glycated albumin also decreased. HbA1c and HOMA-IR did not clearly change. View findings and limitations |
| Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron.PMID 29753693 # | Study conditions — | Findings and scope — Open original paper |
| The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain.PMID 27738640 # | Study conditions — | Findings and scope — Open original paper |
| Sleep and moodReduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study.PMID 32994490 # | Study conditions Randomized, double-blind, placebo-controlled parallel-group trial
| Findings and scope Overall fatigue, work-related fatigue and anger–hostility decreased, with significant time-by-group interactions (p=0.040, 0.020 and 0.045). Other mood improvements were within-group comparisons. View findings and limitations |
| Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.PMID 26514619 # | Study conditions — | Findings and scope — Open original paper |
| A single-arm, open-label, intervention study to investigate the improvement of glucose tolerance after administration of the 5-aminolevulinic acid (5-ALA) in the patients with mitochondrial diabetes mellitus.PMID 33725905 # | Study conditions — | Findings and scope — Open original paper |
| Efficacy and Safety of 5-Aminolevulinic Acid Combined with Iron on Skeletal Muscle Mass Index and Physical Performance of Patients with Sarcopenia: A Multicenter, Double-Blinded, Randomized-Controlled Trial (ALADDIN Study).PMID 37447194 # | Study conditions — | Findings and scope — Open original paper |
| Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness.PMID 36418716 # | Study conditions — | Findings and scope — Open original paper |
| Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.PMID 37653769 # | Study conditions — | Findings and scope — Open original paper |
| Efficacy and Safety of 5-Aminolevulinic Acid for Patients with Symptoms of Late-Onset Hypogonadism: A Preliminary Study.PMID 35118837 # | Study conditions — | Findings and scope — Open original paper |
No papers match. Change the search conditions.
The literature map is an index of research questions and references. Individual assessment of results, doses, funding and COI is limited to the detailed study records. Related reports from the same trial may be included; paper counts are not counts of independent trials.
Explore the research Study Records
Listed doses describe study conditions, not recommended intake.
Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study.
PubMed 32994490DOI: 10.1038/s41598-020-72763-4
- Authors
- Higashikawa F, Kanno K, Ogata A, Sugiyama M.
- Journal
- Scientific reports
- Publication year
- 2020
- Study design
- Randomized, double-blind, placebo-controlled parallel-group trial
- Participants
- 70 people aged 20–64 who regularly experienced physical fatigue
- Dose and intervention
- 3 tablets/day supplied 30 mg of 5-ALA phosphate and 34.5 mg sodium ferrous citrate (3.6 mg iron). The control contained the same iron. The salt mass is reported; it should not be read as 30 mg of free 5-ALA.
- Duration
- 8 weeks
- Outcomes and their role in the study
- Primary: change in overall-fatigue VAS at 8 weeks. Secondary: other fatigue VAS measures and selected POMS2-A mood scores.
- Findings
- Overall fatigue, work-related fatigue and anger–hostility decreased, with significant time-by-group interactions (p=0.040, 0.020 and 0.045). Other mood improvements were within-group comparisons.
- Limitations
- Subjective outcomes over 8 weeks in otherwise healthy adults. Both arms received iron, so the contrast concerns adding 5-ALA phosphate to that regimen. People taking medicines for chronic illness and pregnant or breastfeeding people were excluded.
- Funding
- ALApromo Co., Ltd. The authors state that the funder was not involved in data collection, analysis, interpretation or manuscript preparation.
- Conflict of Interest
- The authors declared no competing interests.
- Scope of source review
- Primary-paper methods, relevant results, limitations and funding/COI checked on 2026-10-24. This record assesses the stated claims, not every analysis in the paper.
5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects.
PubMed 23759263DOI: 10.1016/j.nut.2013.02.008
- Authors
- Higashikawa F, Noda M, Awaya T, Tanaka T, Sugiyama M.
- Journal
- Nutrition (Burbank, Los Angeles County, Calif.)
- Publication year
- 2013
- Study design
- Randomized, double-blind, placebo-controlled trial
- Participants
- 212 people aged 35–70 with mild hyperglycemia
- Dose and intervention
- ALA-P plus iron: 5 mg + 0.6 mg, 5 mg + 1.8 mg, 15 mg + 1.8 mg, or placebo
- Duration
- 12 weeks
- Outcomes and their role in the study
- Fasting blood glucose, 2-hour glucose tolerance test values, glycated albumin, HbA1c and other measures
- Findings
- The 15 mg ALA-P + 1.8 mg iron arm reduced fasting glucose by 2.32 mg/dL and 2-hour glucose by 14.2 mg/dL more than placebo; glycated albumin also decreased. HbA1c and HOMA-IR did not clearly change.
- Limitations
- ALA-P was combined with iron. This is not the same intervention as 5-ALA alone.
- Funding
- The bibliographic funding field lists SBI Pharmaceuticals Co., Ltd., Tokyo, Japan. This does not confirm every funding source.
- Conflict of Interest
- Details have not been verified. This does not mean that no disclosure exists.
- Scope of source review
- Bibliographic information and abstract checked. A full assessment of every item in the paper has not been completed.
Cite this page
LÍFSVARÐA. 5-ALA: How does the focus on heme relate to human trials combining 5-ALA with iron? / Updated 2026-10-24
https://lifsvarda.com/knowledge/5-ala/Edited by LÍFSVARÐA (product brand).Editorial policy
Sources and updates
- Higashikawa F, Noda M, Awaya T, Tanaka T, Sugiyama M. (2013). 5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects.Bibliographic information and abstract checked. A full assessment of every item in the paper has not been completed.
- Higashikawa F, Kanno K, Ogata A, Sugiyama M. (2020). Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study.Primary-paper methods, relevant results, limitations and funding/COI checked on 2026-10-24. This record assesses the stated claims, not every analysis in the paper.
2026-10-11: Human-study coverage, findings and comparisons reviewed. Source-review scope is stated for each study.