Isoleucine amino acid supplement
June 2 2014 by
Ray Sahelian, M.D.

L Isoleucine is one of the branched-chain amino acid which also include leucine and valine. I have not come across any human studies with isoleucine supplement taken orally by itself. Therefore, I am not sure why anyone would take an isoleucine supplement. You can purchase a combination of leucine, isoleucine and valine branched chain amino acids, a BCAA supplement. BCAA also has glutamine amino acid. If you wish to increase muscle mass, consider creatine powder.

Isoleucine health benefit
I have not seen human research regarding the health benefits of taking oral isoleucine supplements alone. An animal study shows improved blood sugar control.

Cancer metastasis
Cancer Res. 2007.  Isoleucine, an essential amino acid, prevents liver metastases of colon cancer by antiangiogenesis. In spite of recent advances in the treatment of colon cancer, multiple liver metastases of colon cancer are still difficult to treat. Some chemotherapeutic regimens have been reported to be efficient, but there is a high risk of side effects associated with these. Here, we show that isoleucine, an essential amino acid, prevents liver metastases in a mouse colon cancer metastatic model. Because isoleucine is a strong inducer of beta-defensin, we first hypothesized that it prevented liver metastases via the accumulation of dendritic cells or memory T cells through up-regulation of beta-defensin. However, neither beta-defensin nor immunologic responses were induced by isoleucine in both mouse livers and spleens. Furthermore, isoleucine prevented liver metastasis in nude mice, which lack T cells and natural killer T cells. Finally, we discovered a novel mechanism of isoleucine: down-regulation of angiogenesis via inhibition of vascular endothelial growth factor, partially through the mammalian target of the rapamycin pathway, independent of hypoxia-inducible factor 1-alpha. Importantly, isoleucine is safe for administration to humans because it does not affect cell viability. Isoleucine could be a novel prophylactic drug for the prevention of liver metastases of colon cancer.

Isoleucine in liver disease
Isoleucine infusion during "simulated" upper gastrointestinal bleeding improves liver and muscle protein synthesis in cirrhotic patients.
Hepatology. 2007. Department of Surgery, Academic Hospital, Maastricht University, Maastricht, The Netherlands.
Upper gastrointestinal (GI) bleeding in cirrhotic patients has a high incidence of mortality and morbidity. Postbleeding catabolism has been hypothesized to be partly due to the low biological value of hemoglobin, which lacks the essential amino acid isoleucine. The aims were to study the metabolic consequences of a "simulated" upper GI bleed in patients with cirrhosis of the liver and the effects of intravenous infusion of isoleucine. The present study investigated hepatic and portal drained viscera protein metabolism selectively in humans. The data show that hepatic and muscle protein synthesis is stimulated by improving the amino acid composition of the upper GI bleed by simultaneous intravenous isoleucine administration.

Diabetes Technol Ther. 2012. The effect of a low-carbohydrate/high-monounsaturated fatty acid liquid diet and an isoleucine-containing liquid diet on 24-h glycemic variability in diabetes patients on tube feeding: a comparison by continuous glucose monitoring. This study compare the effect of various liquid diets on 24-h glycemic variability in diabetes patients on tube feeding. The study included type 2 diabetes patients in whom percutaneous endoscopic gastrostomy had been performed for dysphagia as a sequela of cerebrovascular disease and who had been put on tube feeding with a standard high-carbohydrate liquid diet (HCD). Once stable glycemic control was achieved, these patients were continuously monitored for glucose levels for 5 days on continuous glucose monitoring. Of the 14 patients included, seven were given HCD on day 1, a low-carbohydrate/high-monounsaturated fatty acid liquid diet (LCD) on Days 2 and 3, and a isoleucine-containing liquid diet (ICD), which is known to promote glycemic uptake by skeletal muscle, thus suppressing increases in glucose levels, on Days 4 and 5, with the remaining seven given the same diets but ICD given on Days 2 and 3 and LCD given on Days 4 and 5. All comparisons were made under the same caloric conditions (caloric intake, 800-1200 kcal/day). The 24-h mean glucose level was significantly lower with LCD and ICD than with HCD but was also significantly lower with LCD than with ICD. On the other hand, the SD of 288 glucose levels over a 24-h period, 24-h total area for glycemic fluctuations, and mean amplitude of glycemic excursion were significantly lower with LCD than with HCD or ICD, whereas they did not differ significantly between HCD and ICD. LCD and ICD led to significant decreases in mean glucose levels, compared with HCD. However, of the diets compared, LCD had the greatest effect on glycemic variability in these patients on tube feeding.

Readers ask
I saw your note about why anyone would need to take an isoleucine supplement. What about this study?
Isoleucine, a Blood Glucose-Lowering Amino Acid, Increases Glucose Uptake in Rat Skeletal Muscle in the Absence of Increases in AMP-Activated Protein Kinase Activity. The American Society for Nutritional Sciences J. Nutr. September 2005. Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Incorporated, Naruto, Tokushima and * Department of Animal Science, Utsunomiya University, Utsunomiya, Tochigi, Japan
Leucine and isoleucine were shown to stimulate insulin-independent glucose uptake in skeletal muscle cells in vitro. In this study, we examined the effects of leucine and isoleucine on blood glucose in food-deprived rats and on glucose metabolism in skeletal muscle in vivo. Furthermore, we investigated the possible involvement of the energy sensor, 5'-AMP-activated protein kinase, in the modulation of glucose uptake in skeletal muscle, which is independent of insulin, and also in leucine- or isoleucine-stimulated glucose uptake. Oral administration of isoleucine, but not leucine, significantly decreased the plasma glucose concentration. This is the first report of isoleucine stimulating glucose uptake in rat skeletal muscle in vivo, and these results indicate that there might be a relation between the reduction in blood glucose and the increase in skeletal muscle glucose uptake that occur with isoleucine administration in rats. The alterations in glucose metabolism caused by isoleucine may result in an improvement of the availability of ATP in the absence of increases in AMP-activated protein kinase activity in skeletal muscle.
    Thanks for sending this, but I prefer seeing an actual study in humans with dosages that are reasonable to take by an average person before recommending an isoleucine supplement.