L-Isoleucine
Summary
Isoleucine is one of the three branched-chain amino acids people must get from food; adults need about 19 mg per kg of body weight daily. Single 10 g doses given by tube lowered post-meal glucose in healthy volunteers but not in type 2 diabetes, and a swallowed dose did not (grade D). No trial has tested isoleucine alone for muscle or exercise.
Key facts
- Estimated average requirement 15 mg/kg/day; RDA 19 mg/kg/day (25 mg/kg/day in pregnancy)[1]
- Only single-dose laboratory studies (about 5–16 g); none tested isoleucine supplements over weeks[2][3][4][5]
- 10 g by tube lowered post-meal glucose in healthy people, not in type 2 diabetes; a swallowed dose before a glucose drink had no effect[2][3][4][5]
- 500 mg per capsule; one product lists 2,000 mg per 4-capsule serving[8]
- Oral isoleucine (100 mg/kg) reversed levodopa's effect in people with Parkinson's disease[6]
- 4 graded human outcomes on this page
- October 13, 2026
How it works
ProposedIsoleucine is used to build body proteins and can be broken down for energy in muscle. In healthy volunteers, tube-fed isoleucine lowered post-meal glucose without raising insulin, and the authors linked the effect partly to slower gastric emptying; isoleucine also raised glucagon. As a large neutral amino acid it competes with levodopa for transport into the brain.[2][3][6]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Peak post-meal glucose, C-peptide, glucagon and gastric emptying | Improved | Grade D | Crossover RCT · n = 15 · 2021 Healthy young men Form: L-isoleucine (also leucine and valine arms) · Dose: 10 g by intragastric tube 30 minutes before a mixed-nutrient drink · Duration: Single dose per visit Isoleucine lowered peak post-meal glucose compared with control and valine, and raised glucagon before the drink. Overall gastric emptying did not change. | 34064996 (opens PubMed)Source [2] |
| Post-meal glucose and gastric emptying in type 2 diabetes | No effect | Grade D | Crossover RCT · n = 14 · 2021 Men with type 2 diabetes Form: L-isoleucine (also a leucine arm) · Dose: 10 g by intragastric tube 30 minutes before a mixed-nutrient drink · Duration: Single dose per visit Isoleucine raised insulin and glucagon but did not lower post-meal glucose or slow gastric emptying. | 33310174 (opens PubMed)Source [4] |
| Blood glucose after a mixed-nutrient drink and later energy intake | Improved | Grade D | Crossover RCT · n = 12 · 2016 Healthy lean volunteers Form: L-isoleucine · Dose: 5 g or 10 g by intragastric infusion 15 minutes before the drink · Duration: Single dose per visit 10 g lowered the blood glucose area under the curve and peak glucose without raising insulin; 5 g had no significant effect. Neither dose changed how much people ate at a buffet meal. | 27655440 (opens PubMed)Source [3] |
| Glucose, insulin and gut hormones during an oral glucose tolerance test | No effect | Grade D | Crossover RCT · n = 12 · 2019 Healthy inactive adults (6 women, 6 men; USA) Form: L-isoleucine by mouth (also leucine and leucine + isoleucine arms) · Dose: 0.3 g per kg lean body mass (about 16 g on average) 30 minutes before the glucose drink · Duration: Single dose per visit Isoleucine raised the gut hormone GIP more than leucine or placebo, but did not change blood glucose or insulin. | 31689951 (opens PubMed)Source [5] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Free-form L-isoleucine (powder or capsules) | Varies[8] | No human absorption data for capsules; a 0.3 g/kg lean-mass oral dose changed gut-hormone (GIP) levels within the test period, showing it was absorbed.[5] | No adverse effects were reported in the single-dose laboratory studies cited here.[2][3][5] | Glucose and gut-hormone laboratory studies (single doses) |
| BCAA blends (leucine, isoleucine, valine) | Varies[2] | No head-to-head human data on isoleucine absorption from blends versus free isoleucine.[2] | Not assessed in the isoleucine studies cited here.[2] | Muscle and exercise outcomes (see BCAAs page) |
| Medical isoleucine supplements (maple syrup urine disease) | Varies[7] | No absorption data; the isoleucine dose children needed fell by 18% after switching to a ready-to-use liquid.[7] | Well tolerated, with no adverse effects reported over 56 days in 5 children.[7] | Dietary management of maple syrup urine disease under a metabolic team |
Studied doses
Doses studied in human trials ranged from single 5–10 g doses of isoleucine given by tube to a single swallowed dose of 0.3 g per kg of lean body mass (about 16 g). No trial has tested isoleucine alone over days or weeks.[2][3][4][5]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- LevodopaPK studyLarge neutral amino acids compete with levodopa for transport into the brain: oral isoleucine, leucine or phenylalanine (100 mg/kg) reversed the effect of infused levodopa in people with Parkinson's disease without lowering blood levodopa.[6]
Who should be careful
- People taking levodopa
- Oral isoleucine at 100 mg/kg reversed levodopa's effect in a 1984 study of people with Parkinson's disease.[6]
- Maple syrup urine disease
- Isoleucine intake in this inherited disorder is set and monitored by a metabolic team; over-the-counter products are not a substitute.[7]
- Type 2 diabetes
- Isoleucine raised insulin and glucagon without lowering post-meal glucose in men with type 2 diabetes, so it is not a glucose-lowering option.[4]
- Pregnancy and breastfeeding
- Requirements are higher (RDA 25 mg/kg/day in pregnancy, 30 mg/kg/day in lactation), but no trial has tested isoleucine supplements in these groups.[1]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
- Per serving, not per capsuleOne label lists 2,000 mg of isoleucine per 4-capsule serving, which is 500 mg per capsule; the directions allow 1–4 capsules a day (500–2,000 mg).[8]
- Label dose vs requirementThe full 2,000 mg serving is about 1.5 times the adult RDA for a 70 kg person (1,330 mg), on top of what food provides.[8][1]
- Label dose vs studied doseThe glucose studies used single 5–16 g doses, mostly by tube; label servings are far smaller and have not been tested.[2][3][5][8]
Cost per studied dose, without the sales pitch
Compare any product you already have by the amount it delivers, not by capsule count or front-of-pack weight.
Cost per studied dose
Enter the price, servings and the amount per serving from your label.
Frequently asked questions
How much isoleucine do adults need?
The Institute of Medicine RDA is 19 mg per kg of body weight per day for adults, about 1.3 g for a 70 kg person, from all protein sources.[1]
Does isoleucine lower blood sugar?
Single 10 g doses given by tube lowered post-meal glucose in healthy volunteers, but not in men with type 2 diabetes, and a swallowed dose before a glucose drink had no effect.[2][3][4][5]
Does isoleucine build muscle?
No published trial has tested isoleucine alone for muscle mass, strength or exercise performance. The studies of isoleucine alone were single-dose glucose tests.[2][3][5]
How much isoleucine is in a capsule?
Check the serving size: one product lists 2,000 mg per 4 capsules, so each capsule has 500 mg.[8]
Can isoleucine interfere with medication?
Yes for levodopa: oral isoleucine at 100 mg/kg blocked levodopa's effect in people with Parkinson's disease in a 1984 study.[6]
Sources
- [1]Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Appendix E: DRI values for indispensable amino acids by life stage and gender group. Institute of Medicine, National Academies Press, 2006. guideline
- [2]Comparative Effects of the Branched-Chain Amino Acids, Leucine, Isoleucine and Valine, on Gastric Emptying, Plasma Glucose, C-Peptide and Glucagon in Healthy Men.. Nutrients, 2021. crossover-RCT
- [3]Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers.. Am J Clin Nutr, 2016. crossover-RCT
- [4]Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes.. Diabetes Res Clin Pract, 2021. crossover-RCT
- [5]The Impact of a Large Bolus Dose of l-leucine and l-isoleucine on Enteroendocrine and Pancreatic Hormones, and Glycemia in Healthy, Inactive Adults.. Nutrients, 2019. crossover-RCT
- [6]The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport.. N Engl J Med, 1984. PK-study
- [7]Simplifying supplementation in MSUD: tolerance and acceptability of liquid valine and isoleucine supplements in maple syrup urine disease.. Orphanet J Rare Dis, 2026. open-label
- [8]L-Isoleucine 2,000 mg (Nutricost), DSLD label 306320: 2,000 mg L-isoleucine per 4 capsules (500 mg per capsule), 1–4 capsules daily. NIH Office of Dietary Supplements, Dietary Supplement Label Database, 2024. label
What changed
- Strict adversarial pass: PMIDs re-checked; DSLD dose corrected and verified as 2,000 mg per 4-capsule serving (500 mg per capsule). Levodopa interaction kept; grades held at D (single-dose lab studies).
- First draft rebuilt from scratch after the earlier draft files were lost. Every PMID checked against NCBI esummary (titles and years taken from the record) and abstracts read for each row. Requirement values from the Institute of Medicine DRI Essential Guide, Appendix E. Label dose re-read from the DSLD API: the Nutricost amount is 2,000 mg per 4-capsule serving (500 mg per capsule), not per capsule.