Histidyl-proline diketopiperazine is a cyclic dipeptide otherwise known as Cyclo His-Pro or CHP.
CHP is a cyclic structure formed from the amino acids histidine and proline. It is a major metabolite of thyrotropin-releasing hormone (TRH).
In addition to being a metabolite of TRH, it may be derived from sources other than TRH. Thus, CHP is found throughout the human body.
More specifically, Cyclo His-Pro is found in the central nervous system and gastrointestinal tract. Also in a variety of body fluids including milk, blood, cerebrospinal fluid, and urine.
CHP is also found in many foods including tuna, shrimp, and ham. Some nutritional supplements that contain casein or soy protein may also contain relatively large amounts of CHP.
Research indicates that CHP exhibits a variety of biological functions including…
- appetite suppression
- a reduction of ethanol narcosis (CNS depression)
- a decrease in cholesterol synthesis, and…
- an inhibition of insulin secretion.
CHP is not yet a dietary supplement but does show promise in animal studies.
Supplements that can increase satiety might change chemical signals in the hypothalamus. Because that is where the hunger center appears to be located.
In some research, Cyclo His-Pro shows a neuromodulatory mechanism, which appears to be responsible for the effects of satiety.
The first study reporting the anorectic role of CHP was conducted by Morley et al. Rats who received CHP ate 50-80% less food than control rats.
The researchers claim CHP suppresses dopamine uptake in nerve terminals. Dopamine is considered responsible for eating behavior. The anorectic role of CHP has been supported by subsequent research.
In two separate studies, CHP has been reported to reduce food intake by 20-50% in rats.
Although the exact mechanism of action for CHP is unknown, CHP has been hypothesized to act through a number of mechanisms. For example dopamine, norepinephrine, and serotonin metabolism or even their transporters.
In addition, CHP may act like gut peptides. Food in the GI tract may stimulate the release of peptide hormones that reduce food intake. Circulating CHP has been shown to change following a glucose load.
Plasma CHP showed a rise followed by a fall below baseline and then a recovery toward normal after an oral glucose load. But not after intravenous administration of glucose. This pattern is similar to that reported in humans.
CHP descriptive research in human subjects, it shows that endogenous CHP is distributed throughout the body. The resulting response has similarities with CHP in rats.
The role of CHP administration in humans is unknown due to the lack of research studies and to ethical considerations.
More research is needed to investigate the safety of Cyclo His-Pro before it can be administered to humans.
However, several investigations have focused on changing endogenous CHP levels. Factors that influence it are food consumption and different diseases in humans.
Steiner and coworkers
Anorexia comes with a lack of hunger, which results in malnutrition.
Bulimia, in contrast, is part of a failure to feel satiety even after massive food consumption.
Steiner reported that as anorexics lost weight their CHP levels actually increased. In fact, a 2-kg weight loss was associated with a 42% increase in CHP levels.
This negative correlation between weight loss and CHP levels indicates… The anorexics had less desire to eat with the more weight they lost. But, bulimics responded in just the opposite manner.
As bulimics lost weight, CHP levels dropped as well. This indicates bulimics experience a lack of satiety. Increasing the likelihood of the binge eating and purging that is characteristic of this disease.
Currently, there are some plans to conduct fat-loss studies in adults.
However, one of the problems the researchers are having is finding a manufacturer for CHP.
Small amounts can be purchased for animal studies. But the cost of this dipeptide makes it cost prohibitive to give to humans.
Another important item is that while a reduction in energy intake will result in weight loss, the weight loss may not be permanent.
During a reduction in energy intake, metabolic rate will often decrease to compensate for this reduction in intake.
This reduction in metabolic rate may be linked to a decrease in thyroid hormones.
A decrease in metabolic rate will result in unbalancing the negative and positive calories. This is what causes an increase in body weight.
This is why long-term weight loss cannot be achieved without exercise. Exercise helps maintain and even increase the metabolic rate.
Safety and Toxicity of Cyclo His-Pro
The studies investigating the physiological effects of CHP administration have been careful to document any adverse reactions.
Peters et al administered 400-micron g of CHP intravenously to humans. The results, there were no subjective or objective side effects of CHP administration.
Animal studies have also verified the CHP administration has minimal or no negative side effects.
Nevertheless, more human studies need to be performed.
Exogenous CHP may alter a variety of endocrine and CNS-related activities including…
- Pain responsiveness
- Inhibition of insulin release, and
- Inhibition of prolactin.
Prolactin is a hormone released by the anterior pituitary gland. Many studies have reported that CHP may inhibit basal levels of prolactin and the amount secreted during suckling in women.
In women, prolactin handles milk production and let-down. Thus, a decrease in prolactin may decrease milk production.
If CHP reaches the market as a dietary supplement should not be consumed by women who are breastfeeding because it will appear in breast milk.
Also, prolactin increases testosterone production. By way of direct interaction with receptors in Leydig cells.
Therefore, a decrease in prolactin can result in a decrease in testosterone production. This can change protein synthesis and muscle mass, leading to a change in metabolic rate.
Since CHP may also decrease insulin release! Athletes may find that both glycogen resynthesis and protein synthesis may be decreased.
In male athletes, coupled with the possible decrease in testosterone, Cyclo His-Pro may not be a supplement to consume. This is because of the potential negative effects on muscle mass.
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