4-Hydroxyisoleucine, Fructose, & Insulin Resistance
Being a bodybuilder or even an everyday fitness enthusiast who meticulously plans their diet and trains consistently you are probably well aware of the power of glycogen. This is a formed from glucose in a process called glycogenesis and is stored within skeletal muscle and helps you power through workouts and increase muscle volume. If you have ever felt “flat” it’s more than likely due to the fact you are dehydrated and/or have a low level of glycogen in your muscle. As an athlete whose physical demands require a high level of performance your glycogen status before and during exercise is critical. Moreover, your post workout glycogen replenishment protocol must be thorough to ensure you have proper glycogen status to fuel your next workout whether it be a game or in the gym. If you are insulin resistant, this task can become more difficult.
Unless you’ve been living in a cave or, just aren’t into the bodybuilding scene, there is no doubt insulin plays a role in helping bodybuilders achieve a ridiculous amount of muscle mass. In fact, as surprising as it seems to the general public, insulin is used by professional athletes who rely who seek enhanced glycogen status to sprint faster, have greater endurance, lift stronger for longer, etc. Now you probably thinking taking insulin to boost performance is one dark road you don’t want to travel down. There are a host of risks associated with it (hypoglycemia, blindness, coma, etc) and I really can’t think of anyone who actually likes having to give themselves injections on the regular.
So where does that leave you? You want to increase glycogen status by manipulating insulin dependent glucose disposal in a safe and effective manner? The answer could be 4-hydroxyisoleucine (4-OH-Ile). This potent amino acid extracted from fenugreek (Trigonella foenum-graecum) seeds has the ability to stimulate glucose dependent insulin secretion which helps lower serum glucose levels through enhanced glucose disposal. However, no studies have observed this effect for more than 3 weeks so what about over a larger time line? Is it still effective?
Recently, researchers from the Tabriz University of Medical Sciences in Tabriz, Iran conducted an eight week clinical trial assessing the safety of prolonged use of 4-OH-IIe in mice. What they wanted to investigate was whether or not 4-OH-IIe could help reduce insulin resistance caused by fructose (form of sugar found in fruits) which has been observed in both human and mouse models. What the study revealed is that 4-OH-IIe powerful insulinotropic effect helped reduce fructose related insulin resistance and actually improved various liver related clinical markers commonly associated with insulin resistance and poor glucose disposal. Furthermore, they showed an average decrease in blood glucose levels by 36% compared to controls.
What can we take from this? Well it appears that 4-OH-IIe not only has the ability to help the body utilize glucose more efficiently, but also can help the liver maintain a favorable status on a high fruit diet for eight weeks. In a post workout model, it’s quite possible that 4-OH-IIe can help to increase a more efficient utilization of carbohydrates to replenish depleted glycogen stores in skeletal muscle if you are insulin resistant. It may also help those of you who have a lot of fruit in your diet assimilate fructose more efficiently. This would further insure that the next time you perform physical activity at a high level. Obviously, this is a viable alternative to introducing endogenous insulin and much safer as well for those of you looking to assimilate vast quantities of carbohydrates post workout but have propensity for insulin resistance.
The effect of fenugreek 4-hydroxyisoleucine on liver function biomarkers and glucose in diabetic and fructose-fed rats. Haeri MR, Izaddoost M, Ardekani MR, Nobar MR, White KN. Phytother Res. 2009 Jan;23(1):61-4.
The full text is found for the Tabriz University of Medical Sciences study can be found here:
Post by: deserusan





February 21, 2009 - 1:53 pm MDT at 1:53 pm
great information. we’re both trying to increase muscle and although we’ve read similar studies from various locations, yours was well written.
john and diane
March 22, 2009 - 1:21 am MDT at 1:21 am
Very interesting article, I think it is fantastic that there is a natural solution such as fenugreek to increase muscle and it is great to have the added benefit that it supports the liver, also a very good point that fenugreek will help people with a diet high in fruit as well.
June 7, 2009 - 4:38 pm MDT at 4:38 pm
I didn’t realize Insulin was being used by the bodybuilding community in this way. Thanks for the info!