Ghrelin is a 28 amino acid long peptide that is secreted in the stomach and released into the bloodstream. It is often referred to as the “hunger hormone”. Ghrelin is known to act directly on Ghrelin receptors in the stomach to increase gastric motility and gastric acid secretion. Gastric derived Ghrelin is also known to cross the blood barrier where it activates Ghrelin receptors in parts of the hypothalamus. In short, the activation of these Ghrelin receptors results in increases in activity of certain neuronal systems involved in appetite and energy homeostasis. Activation of hypothalamic Ghrelin receptors also stimulates the release of growth hormone from the pituitary gland in a significant and reproducible manner.
These anabolic and appetite stimulating properties have made Ghrelin a compound of much interest in the medical community – in particular for the management of cachexia. Cachexia is a condition that involves loss of appetite and lean body mass. It is a consequence of diseases such as cancer and AIDS and it often leads to rapid physical deterioration and eventual death.
Even before scientists discovered Ghrelin itself, they knew that its receptor existed and several synthetic Ghrelin analogs had already been developed. Several of these were small peptide molecules such as GHRP-2 and Hexarelin, but orally active non peptidyl Gherlin analogs such as Ibutamoren (MK-677) were also developed and tested. All of these compounds shared the classical effects seen with natural Ghrelin – namely increases in appetite and elevations in circulating GH and IGF-1.
Today there are dozens of Ghrelin analogs in the drug development pipeline but none have yet achieved FDA approval and made it to market. Many of these however are being sold through “research chemical” websites to athletes (though such sales are legally questionable at a minimum). Most of these need to be injected although at least one (Ibutamoren) works orally.
Remarkably, there appears to be an actual natural herbal medicine from Japan that has the same end results as the synthetic Ghrelin analogs. This concoction is known as Rikkunshito, and it consists of a mixture of extractions from eight different herbal constituents.
Rikkunshito is classified in Japan as a “Kampo” medicine. Kampo medicines are traditional herbal medicines which have been approved for medicinal use by the Japanese Ministry of Health and Welfare.
The traditional use of Rikkunshito has been to treat indigestion / heartburn, as well as stimulate the appetite. Recent research has shown that Rikkunshito regulates the secretion, receptor sensitization (in hypothalamus), and degradation of Ghrelin. Numerous studies (several on actual humans) have demonstrated this effect and shown it to be effective in increasing appetite, gastric motility, and body weight in patients suffering from cachexia / anorexia syndrome.
Two chemical constituents of Rikkunshito proposed to be responsible for these effects are Hesperidin and Atractylodin. Hesperidin is thought to increase Ghrelin secretion via antagonizing a subtype serotonin receptor known as the 5-HT2b/2c receptor. Atractylodin is believed to sensitize the ghrelin receptor, thereby amplifying the physiological effects of the increased ghrelin secreted into the bloodstream.
The literature on this herbal medicine is quite impressive in regards to its effects on Ghrelin activity and its effects on reversing cachexia (improving appetite and digestion, as well as improving body weight). I haven’t found any literature directly documenting its effect on growth hormone / IGF-1, however one would expect it to have that property as it works by potentiating Gherlin secretion and signaling.