Home Ingredients 5-ALA with Sodium Ferrous Citrate (5-Aminolevulinic Acid Phosphate)
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5-ALA with Sodium Ferrous Citrate (5-Aminolevulinic Acid Phosphate)

Evidence Level
Limited
8 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

5-aminolevulinic acid (5-ALA) is the compound the body uses as the first building block of heme. As a supplement it is sold as 5-ALA phosphate combined with sodium ferrous citrate (SFC), an iron source; in Japan, SBI ALApromo markets it as a Food with Function Claims product for temporary fatigue. This supplement is not the prescription drug: 5-ALA hydrochloride is an oral imaging agent used during brain tumor surgery and a topical gel or solution used with light treatment of skin lesions. The oral drug dose (20 mg per kg of body weight) is far larger and requires limiting sunlight and room light for 48 hours; the supplement trials did not report light reactions. Small trials, most funded by the makers, found less self-rated fatigue at 30 mg a day, lower blood sugar after a glucose drink in adults with raised glucose, and lower oxygen use during exercise in older women. HbA1c did not change, and muscle mass did not change in older adults.

Studied Dose 5 to 50 mg 5-ALA phosphate with 0.6 to 6.1 mg iron as SFC daily for 12 weeks (glucose trials); 30 mg with 34.5 mg SFC for 8 weeks (fatigue); 100 mg with 115 mg SFC for 7 days (exercise). Up to 200 mg with 229 mg SFC was tested over 12 weeks.
Active Compound 5-aminolevulinic acid phosphate (5-ALA phosphate), a salt of 5-ALA, combined with sodium ferrous citrate (SFC) as an iron source. In the trial products, 57.4 mg of SFC supplied 6.08 mg of iron and 34.5 mg supplied 3.6 mg. FDA's notification list describes ALA phosphate made by fermentation using Rhodobacter sphaeroides.

Benefits

Less self-rated fatigue in adults who feel tired every day

In 70 adults who felt physically tired every day, 30 mg of 5-ALA phosphate a day for 8 weeks lowered overall fatigue on a 100 mm scale by 14.4 mm, against 3.4 mm in a control group that took the same iron (SFC) without 5-ALA, so the test isolates 5-ALA rather than the combination (p = 0.040 over time). The 5-ALA group started 7 mm higher. The maker funded the study.

Supported by Trial 4, Trial 5

Blood sugar after a glucose drink in adults with raised glucose

In two 12 week placebo-controlled trials of adults with prediabetes (212 in Japan, 154 in Hawaii), 5-ALA phosphate with SFC lowered blood sugar 2 hours after a glucose tolerance drink more than placebo; in Japan the reported effect was at the highest dose (15 mg). HbA1c did not change in Japan and was borderline (p = 0.07) in Hawaii. Fasting glucose fell 2.3 mg/dL more than placebo at that dose.

Supported by Trial 1, Trial 2

Energy cost of exercise and walking training in older women

In two 7 day crossover trials by one university group with maker co-authors (10 women aged about 65 and 15 aged about 78), 100 mg of 5-ALA phosphate with 115 mg SFC a day lowered oxygen use and blood lactate during a cycling test and raised fast-walking time versus placebo (the first trial's placebo had no iron). In 14 young adults, 25 mg a day for 4 weeks did not change heart rate or lactate during cycling.

Supported by Trial 5, Trial 6

Hand grip strength in older adults with low muscle mass

In 90 adults aged 65 or older with sarcopenia, 50 to 150 mg of 5-ALA a day for 12 weeks did not change skeletal muscle mass, the main outcome, compared with SFC alone. Hand grip, a secondary measure, held steady or rose by up to 1.0 kg while it fell 0.8 kg on SFC alone. Calf size, other physical tests and quality of life showed no steady change.

Supported by Trial 8

Mood and coping ratings in a 12 week glucose trial

In the Hawaii trial of 154 adults, a later questionnaire analysis found better ratings for coping, sense of effort and loneliness after 12 weeks on 5-ALA than on placebo, more at 50 mg than at 15 mg. These were secondary questionnaire items reported years after the main results, and the trial ran under a contract from the maker.

Supported by Trial 2

Mechanism of action

1

First building block of heme

5-ALA is made by the enzyme ALA synthase, the first step of heme synthesis, which uses vitamin B6 (as P-5-P) as its cofactor. Later steps turn 5-ALA into protoporphyrin IX, and iron is then inserted to form heme, the oxygen-binding part of hemoglobin and part of the cytochromes that produce energy in mitochondria.

2

Why iron is added

Trial authors state that SFC is included to support the final step of heme synthesis, where iron joins protoporphyrin IX, and to prevent protoporphyrin IX from building up, since that intermediate might cause skin damage on exposure to light. The proposed benefit of the combination is better mitochondrial energy production, which has not been measured directly in these trials.

3

Heme oxygenase-1 in blood cells

In an open-label study in healthy men by mostly maker scientists, a single 600 mg dose of 5-ALA with 942 mg SFC raised heme oxygenase-1, described by the authors as a major anti-inflammatory enzyme, in blood immune cells at 8 hours. Neither 5-ALA nor SFC alone did so. This dose is far higher than supplement servings.

Clinical trials

1
5-ALA Phosphate With Iron for 12 Weeks: Glucose in 212 Adults With Raised Glucose
PubMed

Double-blind, randomized, placebo-controlled trial of three once-daily doses for 12 weeks: 5 mg 5-ALA phosphate with 0.6 mg iron as SFC, 5 mg with 1.8 mg iron, or 15 mg with 1.8 mg iron; funding and author ties are not stated in the PubMed record (Higashikawa et al. 2013, Nutrition)

212 adults in Japan aged 35 to 70 with fasting glucose of 105 to 125 mg/dL or HbA1c of 6.1 to 7.1 percent.

The highest dose lowered fasting glucose 2.32 mg/dL (p = 0.029), glycoalbumin 0.22 percent (p = 0.031) and 2-hour glucose tolerance test values 14.2 mg/dL (p = 0.025) more than placebo. HbA1c, fasting insulin, 1,5-anhydro-D-glucitol and HOMA-IR showed no appreciable changes. The abstract reports between-group results only for the highest dose.

2
5-ALA Phosphate With SFC 15 or 50 mg: Hawaii 12 Week Glucose Trial
PubMed

Double-blind, randomized, placebo-controlled parallel trial; 15 mg 5-ALA phosphate with 17.2 mg SFC (1.82 mg iron) or 50 mg with 57.4 mg SFC (6.08 mg iron) once daily for 12 weeks; SBI Pharmaceuticals provided the product and a contract to the University of Hawaii; a 2018 paper reported mood questionnaires from the same trial (Rodriguez et al. 2012, Clin Transl Sci)

154 adults aged 40 to 70 in Honolulu with HbA1c of 5.8 to 7.0 percent at screening.

Two-hour glucose after an oral glucose tolerance test declined more than on placebo (p = 0.02), more so in people starting above 140 mg/dL (p = 0.005 for 15 mg and p = 0.02 for 50 mg). HbA1c, the other main outcome, showed a similar trend of borderline significance (p = 0.07). No untoward effects were reported. In the later questionnaire analysis, coping (p = 0.004) and sense of effort (p = 0.002) improved with 5-ALA.

3
5-ALA Phosphate With SFC up to 200 mg: 12 Week Safety Trial in Bahrain
PubMed

Randomized, single-blind, placebo-controlled dose escalation pilot; 100 mg 5-ALA with 114.72 mg SFC a day rising to 200 mg with 229.42 mg SFC from week 4, in two divided doses, for 12 weeks; registered NCT02481141; sponsored by SBI Pharmaceuticals, with six SBI staff among the authors (Al-Saber et al. 2016, J Diabetes Res)

53 adults in Bahrain with type 2 diabetes not controlled on one or more oral medications; 35 received 5-ALA with SFC and 18 placebo.

The primary endpoint, adverse events, did not differ significantly (45.7 versus 27.8 percent, p = 0.206); gastrointestinal events were most common (28.6 versus 16.7 percent), and six people on 5-ALA and one on placebo withdrew because of adverse events. Liver, kidney and iron tests showed no clinically significant changes, and hypoglycemia did not differ. HbA1c did not differ between groups, and fasting and after-breakfast glucose fell in both groups.

4
5-ALA Phosphate 30 mg for 8 Weeks: Fatigue in 70 Tired Adults
PubMed

Randomized, double-blind, placebo-controlled parallel trial; 30 mg 5-ALA phosphate with 34.5 mg SFC (3.6 mg iron) a day for 8 weeks, against 34.5 mg SFC alone; registered UMIN000031528; tablets provided by SBI ALApromo and study funded by ALApromo (Higashikawa et al. 2020, Sci Rep)

70 adults aged 20 to 64 in Japan who felt physical fatigue daily; 35 per group, about three quarters women.

The primary outcome, overall fatigue on a 100 mm scale, fell 14.4 mm on 5-ALA versus 3.4 mm on SFC alone (time by group p = 0.040), from a higher starting score (73.0 versus 66.0 mm; 58.6 versus 62.6 mm at week 8). With SFC in both groups, this tests 5-ALA itself. Work-related fatigue (p = 0.020) and anger-hostility (p = 0.045) also fell more. Apart from one participant who withdrew, no obvious adverse events possibly related to 5-ALA were detected.

5
5-ALA Phosphate With SFC for 7 Days: Exercise Efficiency in Older Women
PubMed

Placebo-controlled, double-blind crossover trial; 100 mg 5-ALA phosphate with 115 mg SFC a day (12 mg iron) or a placebo without SFC for 7 days each, 2 week washout; funded by a Japan Society for the Promotion of Science grant, supplements from SBI ALApromo, three authors from SBI Pharmaceuticals R&D (Masuki et al. 2016, J Appl Physiol)

10 women aged about 65 who had done interval walking training for over a year.

During graded cycling, oxygen use fell 12 percent, carbon dioxide output 11 percent and blood lactate 16 percent on 5-ALA, with no change on placebo, and the reductions were larger than on placebo (p < 0.05). Training days, impulse and time at fast walking were 42, 102 and 69 percent higher on 5-ALA.

6
5-ALA Phosphate With SFC for 7 Days: Walking Training in Women Over 75
PubMed

Placebo-controlled, double-blind crossover trial; 100 mg 5-ALA phosphate with 115 mg SFC a day or placebo for 7 days each during interval walking training, 12 day washout; two authors from SBI Pharma R&D (Ichihara et al. 2021, Exp Gerontol)

15 women aged about 78 with no exercise habit.

Rises in oxygen use and carbon dioxide output during graded cycling were smaller on 5-ALA (both p < 0.01), with 13 percent lower lactate (p = 0.012), and none of these changed on placebo. Energy expenditure and time during fast walking were 25 percent (p = 0.032) and 21 percent (p = 0.022) higher than on placebo.

7
5-ALA 25 mg With SFC for 4 Weeks: Aerobic Capacity in 14 Young Adults
PubMed

Placebo-controlled, double-blind trial with two orders (4 weeks of 5-ALA then 4 weeks of placebo, or the reverse) and no washout; 25 mg 5-ALA with 29 mg SFC a day, placebo also containing 29 mg SFC; funded by SBI ALApromo, which supplied the products (Saga et al. 2024, Int J Mol Sci)

14 healthy volunteers in Japan, 7 men and 7 women.

The primary analysis found no group, time or interaction differences in heart rate, blood lactate or oxidative stress markers during cycling. In a secondary analysis, biological antioxidant potential and its ratio to oxidative stress differed from placebo at the highest exercise intensity after 4 weeks of 5-ALA (p < 0.05).

8
5-ALA With SFC for 12 Weeks: Muscle Mass and Grip in Older Adults (ALADDIN)
PubMed

Multicenter, double-blind, randomized controlled trial; 50, 100 or 150 mg 5-ALA with 29 mg SFC (3.0 mg iron), or 100 mg with 57 mg SFC (6.0 mg iron), against 29 mg SFC alone, for 12 weeks; registered jRCTs031200433; the lead author received study funding from SBI Pharmaceuticals (Tamura et al. 2023, Nutrients)

90 adults aged 65 or older in Japan with sarcopenia (safety set of 15 to 20 per group).

The primary endpoint, change in skeletal muscle mass index, did not differ from the SFC only group. Hand grip, a secondary endpoint, fell 0.8 kg on SFC alone and changed by +0.1 to +1.0 kg on 5-ALA (p from below 0.001 to 0.06 across groups), with no clear dose pattern. Other physical function and quality of life measures showed no steady changes, and adverse event rates did not differ.

Side effects and drug interactions

Common Potential side effects

This page covers the 5-ALA phosphate supplement, not the prescription drug. Prescription 5-ALA hydrochloride (Gleolan, taken by mouth at 20 mg/kg before brain tumor surgery) requires reducing exposure to sunlight and room lights for 48 hours; that warning applies to the drug dose, which for a 70 kg adult is about 1,400 mg at once.
Digestive upset was the most common complaint. In a 12 week trial of up to 200 mg a day in 53 adults, any adverse event occurred in 45.7 percent on 5-ALA and 27.8 percent on placebo (not significant), gastrointestinal events in 28.6 versus 16.7 percent, and six people on 5-ALA versus one on placebo stopped because of adverse events.
Laboratory safety: in that 12 week trial, liver, kidney and iron blood tests showed no clinically significant changes; in a 12 week trial in 90 older adults, adverse event rates did not differ from SFC alone.
Light sensitivity: protoporphyrin IX, made from 5-ALA, can sensitize skin to light at drug doses. Light-sensitivity reactions were not among the adverse events described in the supplement-dose trials cited here, which lasted 12 weeks or less.
SFC is an iron source: it supplied 0.6 to 12 mg of iron a day in the efficacy trials, and the 200 mg safety trial used twice the SFC of the 12 mg dose. People with hereditary hemochromatosis or other iron overload should not take added iron unless a blood test shows a need. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6; keep out of reach of children. See the iron page.
At much higher doses (750 mg 5-ALA phosphate with 435 mg SFC a day) in a trial in people with COVID-19, gastrointestinal events such as decreased appetite, constipation and vomiting occurred in 22.7 percent, which the authors attributed mainly to the iron; that trial excluded people with porphyria, hemochromatosis, photosensitivity or photosensitizing drugs. It showed no effect on viral load or symptom scores and is cited only for safety.

Important Drug interactions

Photosensitizing drugs: the prescription 5-ALA label lists St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones and tetracyclines as phototoxic drugs to avoid around a drug dose. No interaction study at supplement doses was found; ask a pharmacist before combining.
Glucose-lowering medication: in a 12 week trial in adults taking oral diabetes medicines, hypoglycemia did not differ from placebo at up to 200 mg a day, but anyone on these drugs should monitor blood sugar when starting.
Drugs affected by iron: the SFC iron can lower absorption of tetracycline and quinolone antibiotics and levothyroxine, as with other iron supplements; see the iron page for spacing advice.

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Frequently asked questions about 5-ALA with Sodium Ferrous Citrate (5-Aminolevulinic Acid Phosphate)

Is 5-ALA with SFC the same as the prescription 5-ALA drug?

No. Prescription products use 5-ALA hydrochloride: Gleolan is a single oral dose of 20 mg/kg used to make tumor tissue visible during brain surgery, and Ameluz and Levulan Kerastick are applied to skin lesions with light therapy. The supplement uses 5-ALA phosphate with iron at 5 to 200 mg a day. The drug uses are a different product, dose and purpose and are not supplement benefits.

What has 5-ALA with SFC been studied for?

Small trials, mostly funded by the makers, tested it for daily tiredness (lower fatigue ratings at 30 mg a day for 8 weeks), blood sugar after a glucose drink in adults with raised glucose (lower 2-hour values, HbA1c unchanged), oxygen use during exercise in older women, and muscle mass in older adults (no change in mass, a small grip difference).

How much iron does a 5-ALA with SFC supplement provide?

It depends on the SFC amount. In the trials, 34.5 mg of SFC supplied 3.6 mg of iron, 57.4 mg supplied 6.08 mg and 115 mg supplied about 12 mg. Count this iron with any multivitamin or iron supplement, and avoid added iron with hemochromatosis or other iron overload unless a doctor advises it. Keep iron-containing products out of reach of children.

Can 5-ALA supplements make skin sensitive to sunlight?

Light sensitivity is a known effect at the prescription drug dose, which calls for reducing exposure to sunlight and room lights for 48 hours. The supplement trials cited here, at 5 to 200 mg a day for up to 12 weeks, did not describe light-sensitivity reactions, and trial authors state the iron is added partly to limit buildup of the light-sensitive intermediate. Long-term data are lacking, so take care if you use photosensitizing medicines.

What is 5-ALA with Sodium Ferrous Citrate?

5-aminolevulinic acid (5-ALA) is the compound the body uses as the first building block of heme. As a supplement it is sold as 5-ALA phosphate combined with sodium ferrous citrate (SFC), an iron source; in Japan, SBI ALApromo markets it as a Food with Function Claims product for temporary fatigue.

What is 5-ALA with Sodium Ferrous Citrate used for?

5-ALA with Sodium Ferrous Citrate is researched primarily for Energy and Metabolic Health. In 70 adults who felt physically tired every day, 30 mg of 5-ALA phosphate a day for 8 weeks lowered overall fatigue on a 100 mm scale by 14.4 mm, against 3.

What is the recommended dosage of 5-ALA with Sodium Ferrous Citrate?

The clinically studied dose is 5 to 50 mg 5-ALA phosphate with 0.6 to 6.1 mg iron as SFC daily for 12 weeks (glucose trials); 30 mg with 34.5 mg SFC for 8 weeks (fatigue); 100 mg with 115 mg SFC for 7 days (exercise). Up to 200 mg with 229 mg SFC was tested over 12 weeks. Always follow the product label and check with a healthcare provider for personal advice.

Is 5-ALA with Sodium Ferrous Citrate safe, and does it have side effects?

Side effects and cautions reported for 5-ALA with Sodium Ferrous Citrate include: This page covers the 5-ALA phosphate supplement, not the prescription drug. Prescription 5-ALA hydrochloride (Gleolan, taken by mouth at 20 mg/kg before brain tumor surgery) requires reducing exposure to sunlight and room lights for 48 hours; that warning applies to the drug dose… It may also interact with some medications. 5-ALA with Sodium Ferrous Citrate is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does 5-ALA with Sodium Ferrous Citrate interact with any medications?

Possible interactions include: Photosensitizing drugs: the prescription 5-ALA label lists St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones and tetracyclines as phototoxic drugs to avoid around a drug dose. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for 5-ALA with Sodium Ferrous Citrate?

NutraSmarts rates the evidence for 5-ALA with Sodium Ferrous Citrate as Limited (2 out of 5). It is backed by 8 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(16 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Rodriguez BL, Curb JD, Davis J, Shintani T, Perez MH, Apau-Ludlum N, Johnson C, Harrigan RC. Use of the dietary supplement 5-aminiolevulinic acid (5-ALA) and its relationship with glucose levels and hemoglobin A1C among individuals with prediabetes. Clin Transl Sci. 2012;5(4):314-20. doi: 10.1111/j.1752-8062.2012.00421.x.PubMedUsed to support: Double-blind randomized trial in 154 adults aged 40 to 70 in Hawaii with HbA1c of 5.8 to 7.0 percent, given a 15 mg or 50 mg 5-ALA capsule or placebo for 12 weeks. Two-hour glucose after an oral glucose tolerance test fell more than on placebo (p = 0.02), more so in those starting above 140 mg/dL. HbA1c showed a similar trend of borderline significance (p = 0.07). No untoward effects were reported.
  2. Aquino RK, Perez M, Sil P, Shintani T, Harrigan R, Rodriguez B. The Relationship of 5-Aminolevulinic Acid on Mood and Coping Ability in Prediabetic Middle Aged and Older Adults. Geriatrics (Basel). 2018;3(2):17. doi: 10.3390/geriatrics3020017.PubMedUsed to support: Secondary questionnaire analysis of the same 154 person Hawaii trial. Lists the capsule contents (15 mg 5-ALA phosphate with 17.2 mg SFC, 1.82 mg iron; or 50 mg with 57.4 mg SFC, 6.08 mg iron) and states that SBI Pharmaceuticals provided the supplement and a contract to the university. After 12 weeks, 5-ALA was associated with better coping (p = 0.004) and sense of effort (p = 0.002), with a dose relationship for effort, loneliness and coping.
  3. Higashikawa F, Noda M, Awaya T, Tanaka T, Sugiyama M. 5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects. Nutrition. 2013;29(7-8):1030-6. doi: 10.1016/j.nut.2013.02.008.PubMedUsed to support: Double-blind randomized trial in 212 adults aged 35 to 70 with fasting glucose of 105 to 125 mg/dL or HbA1c of 6.1 to 7.1 percent, testing three doses of 5-ALA phosphate with iron as SFC or placebo for 12 weeks. The 15 mg dose with 1.8 mg iron lowered fasting glucose (2.32 mg/dL), glycoalbumin and 2-hour glucose tolerance test values (14.2 mg/dL) more than placebo; HbA1c, fasting insulin and HOMA-IR showed no appreciable changes.
  4. Al-Saber F, Aldosari W, Alselaiti M, Khalfan H, Kaladari A, Khan G, Harb G, Rehani R, Kudo S, Koda A, Tanaka T, Nakajima M, Darwish A. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain. J Diabetes Res. 2016;2016:8294805. doi: 10.1155/2016/8294805.PubMedUsed to support: Randomized, single-blind, placebo-controlled dose escalation pilot in 53 adults in Bahrain with type 2 diabetes on oral medication, rising from 100 mg to 200 mg 5-ALA with 229.42 mg SFC a day over 12 weeks (registered NCT02481141). Safety was the primary endpoint: adverse events did not differ significantly (45.7 versus 27.8 percent, p = 0.206), gastrointestinal events were most common, and hypoglycemia did not differ. HbA1c did not differ between groups. Sponsored by SBI Pharmaceuticals; six authors were SBI staff.
  5. Higashikawa F, Kanno K, Ogata A, Sugiyama M. Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study. Sci Rep. 2020;10(1):16004. doi: 10.1038/s41598-020-72763-4.PubMedUsed to support: Double-blind randomized trial in 70 adults aged 20 to 64 with daily physical tiredness (registered UMIN000031528). Both groups took 34.5 mg SFC a day; one group also took 30 mg 5-ALA phosphate for 8 weeks. The primary outcome, overall fatigue on a 100 mm scale, fell 14.4 mm versus 3.4 mm (interaction p = 0.040), and work-related fatigue and anger-hostility scores also fell more. Tablets were provided by SBI ALApromo and the study was funded by ALApromo.
  6. Masuki S, Morita A, Kamijo Y, Ikegawa S, Kataoka Y, Ogawa Y, Sumiyoshi E, Takahashi K, Tanaka T, Nakajima M, Nose H. Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women. J Appl Physiol (1985). 2016;120(1):87-96. doi: 10.1152/japplphysiol.00582.2015.PubMedUsed to support: Double-blind placebo-controlled crossover trial in 10 women aged about 65 already doing interval walking training: 100 mg 5-ALA phosphate with 115 mg SFC a day for 7 days. Oxygen use, carbon dioxide output and blood lactate during graded cycling fell (by 12, 11 and 16 percent) only on 5-ALA, and fast-walking training days, impulse and time were higher than on placebo. Funded by a Japan Society for the Promotion of Science grant; supplements from SBI ALApromo; three authors were from SBI Pharmaceuticals R&D. The authors note that the iron dose was 12 mg a day.
  7. Ichihara Y, Masuki S, Uchida K, Takahashi K, Nakajima M, Nose H. Effects of 5-aminolevulinic acid with iron supplementation on respiratory responses to graded cycling and interval walking training achievement in older women over 75 yrs. Exp Gerontol. 2021;150:111356. doi: 10.1016/j.exger.2021.111356.PubMedUsed to support: Double-blind placebo-controlled crossover trial in 15 women aged about 78 with no exercise habit: 100 mg 5-ALA phosphate with 115 mg SFC a day for 7 days of interval walking training. Rises in oxygen use and carbon dioxide output during graded cycling were smaller and lactate was 13 percent lower only on 5-ALA, and energy expenditure and time during fast walking were 25 and 21 percent higher than on placebo. Two authors were from SBI Pharma R&D.
  8. Saga N, Hu A, Yamaguchi T, Naraoka Y, Kobayashi H. The Impact of 5-Aminolevulinic Acid Supplementation on Redox Balance and Aerobic Capacity. Int J Mol Sci. 2024;25(2):988. doi: 10.3390/ijms25020988.PubMedUsed to support: Double-blind placebo-controlled trial in 14 healthy young adults: 25 mg 5-ALA with 29 mg SFC a day for 4 weeks, with placebo containing the same SFC, in two orders without a washout. The primary analysis found no differences in heart rate, lactate or oxidative stress markers. In a secondary analysis, an antioxidant potential marker and its ratio to oxidative stress differed at the highest exercise intensity at week 4. Funded by SBI ALApromo, which supplied the products. The authors state SFC is included to prevent buildup of protoporphyrin IX, which might cause skin photodamage.
  9. Tamura Y, Kaga H, Abe Y, Yoshii H, Seino H, Hiyoshi T, Kuribayashi N, Inoue I, Watada H. 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). Nutrients. 2023;15(13):2866. doi: 10.3390/nu15132866.PubMedUsed to support: Multicenter double-blind randomized trial (ALADDIN, jRCTs031200433) in 90 adults aged 65 or older with sarcopenia given 50, 100 or 150 mg 5-ALA with 29 mg SFC, or 100 mg with 57 mg SFC, versus 29 mg SFC alone, for 12 weeks. The primary endpoint, change in skeletal muscle mass index, did not differ. Hand grip, a secondary endpoint, increased or tended to increase versus the SFC only group, with no steady change in other physical function or quality of life measures. Adverse event rates did not differ. The lead author received study funding from SBI Pharmaceuticals.
  10. Tanaka T, Tashiro M, Ota K, Fujita A, Sawai T, Kadota J, Fukuda Y, Sumiyoshi M, Ide S, Tachikawa N, Fujii H, Hibino M, Shiomi H, Izumida M, Matsui K, Yamauchi M, Takahashi K, Yamanashi H, Sugimoto T, Akabame S, Umeda M, Shimizu M, Hosogaya N, Kosai K, Takeda K, Iwanaga N, Ashizawa N, Hirayama T, Takazono T, Yamamoto K, Imamura Y, Miyazaki T, Kobayashi Y, Ariyoshi K, Mukae H, Yanagihara K, Kita K, Izumikawa K. Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial. Medicine (Baltimore). 2023;102(34):e34858. doi: 10.1097/MD.0000000000034858.PubMedUsed to support: Open-label randomized phase II trial in 50 patients with mild to moderate COVID-19 given 750 mg 5-ALA phosphate with 435 mg SFC a day for 7 days, then 450 mg with 261 mg SFC a day for 7 days, versus no study product. Viral load and clinical symptom scores did not differ. Gastrointestinal adverse events (decreased appetite, constipation, vomiting) occurred in 22.7 percent of the 5-ALA group. People with photosensitivity, photosensitizing drugs, porphyria or hemochromatosis were excluded. Funded by Neopharma Japan; one author was a Neopharma Japan employee. Cited for safety context only.
  11. Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li XK. 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. Eur J Pharmacol. 2018;833:25-33. doi: 10.1016/j.ejphar.2018.05.009.PubMedUsed to support: Open-label, non-randomized study in healthy men without a placebo group. A single dose of 600 mg 5-ALA with 942 mg SFC raised heme oxygenase-1 in blood immune cells at 8 hours, while 5-ALA or SFC alone did not; no clear dose relationship was found from 150 to 600 mg. Four of six authors were from SBI Pharmaceuticals.
  12. NX Development Corp. GLEOLAN (aminolevulinic acid hydrochloride) powder, for solution: prescribing information (DailyMed). U.S. National Library of Medicine, DailyMed. 2024;Label revised 11/2024; accessed 2026..SourceUsed to support: Not PubMed-indexed. Prescription drug label: oral aminolevulinic acid hydrochloride, 20 mg/kg taken about 3 hours before anesthesia, as an aid to see malignant tissue during surgery for suspected high-grade glioma. Patients should reduce exposure to sunlight or room lights for 48 hours after dosing, and phototoxic drugs (such as St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones and tetracyclines) should be avoided for 24 hours around the procedure.
  13. Biofrontera Inc. AMELUZ (aminolevulinic acid hydrochloride) gel, 10%: prescribing information (DailyMed). U.S. National Library of Medicine, DailyMed. 2026;Label revised 9/2026; accessed 2026..SourceUsed to support: Not PubMed-indexed. Prescription topical gel for use with red light photodynamic therapy to treat mild to moderate actinic keratoses and superficial basal cell carcinoma in adults; for topical use only.
  14. Sun Pharmaceutical Industries, Inc. LEVULAN KERASTICK (aminolevulinic acid hydrochloride) topical solution, 20%: prescribing information (DailyMed). U.S. National Library of Medicine, DailyMed. 2024;DailyMed label information dated September 12, 2024; accessed 2026..SourceUsed to support: Not PubMed-indexed. Prescription topical solution for the treatment of minimally to moderately thick actinic keratoses of the face, scalp or upper extremities; for external use only.
  15. U.S. Food and Drug Administration. Submitted 75-Day Premarket Notifications for New Dietary Ingredients (spreadsheet). U.S. Food and Drug Administration. 2026;Accessed 2026..SourceUsed to support: Not PubMed-indexed. FDA's list of new dietary ingredient notifications includes No. 667, ALA phosphate produced by fermentation using Rhodobacter sphaeroides (ALA Plus), from SBI ALApromo (submitted August 2, 2010; FDA response December 21, 2010), and No. 1094, 5-aminolevulinic acid phosphate with sodium ferrous citrate (SFC), from Neopharma Inc. (submitted October 18, 2018; FDA response December 19, 2018). The list does not state the content of FDA's responses.
  16. Yakuji Nippo. SBI ALApromo launches Food with Function Claims product ALAplus Gold for fatigue reduction (in Japanese). Yakuji Nippo. 2022;Published June 6, 2022; accessed 2026..SourceUsed to support: Not PubMed-indexed. Japanese trade news report that SBI ALApromo released a Food with Function Claims product containing its 5-aminolevulinic acid phosphate, with the stated function of reducing temporary fatigue from work in daily life, at 3 tablets a day.