The tiny titans of life: cyclic Glycine-Proline
Article written by Vishakha Mahajan (PhD.), Research & Innovation Scientist, The cGP Lab Limited.
Published 1 March 2024
People take supplements to improve or optimize their health. So what happens when you look at the label, and the ingredient list is filled with unrecognizable additives?
Ageing is a natural part of life that is often accompanied by physiological and psychological changes. While routine tasks become challenging, the plethora of experiences and memories enrich each moment, offering fulfilment despite the inevitable slowing pace and altering dynamics of health and relationships.
Our brain is the command centre that enables us to be who we are, it controls our thoughts, memory, movement and emotions by complex and tightly regulated mechanisms. With an increase in life expectancy and extended health span, maintaining a healthy brain has become increasingly important in the pursuit of vitality and longevity.
I noticed a huge deterioration in my overall mental abilities. I struggled to concentrate, my mind wasn’t as sharp, and I noticed that my motivation at work became less.”
This is the story of T Probert, and many others suffering from the onset of age-related symptoms. In this demographic transition of an ever-growing ageing population, there is an increased burden of neurological disorders and challenges, making the preservation of brain health is an imperative endeavour.
Introducing cGP
Cyclic Glycine-Proline (cGP) is an endogenous molecule with a unique mechanism of action. It works by normalising Insulin-like Growth Factor-1 (IGF-1) which is essential for several biological processes across the life stages.
IGF-1 plays a pivotal role in brain development, memory, cognitive function, and recovery from brain injury through cerebral vascular regeneration and remodelling. Declining levels of IGF-1 are associated with age and studies discovered reduced levels in people over 60 years of age. Low IGF-1 levels are associated with brain ageing and the onset of mild cognitive impairment as well as implicated in the progression of neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease and dementia. Advancements in research have confirmed a connection between healthy brain ageing and improved health span, highlighting the importance of maintaining optimal IGF-1 levels through later adulthood. The brain is a blood vessel rich organ and requires constant blood flow to function properly. As we age, this blood flow reduces, compromising brain health. This is validated by a study that evaluated 234 adults aged 36–90, suggesting that blood flow to the brain decreases as we age, with grey matter being the first area to be affected after the age of 50.
The role of IGF-1 in maintaining blood vessel health and regulating blood flow has been long-studied and established. The brain’s smallest blood vessels (capillaries) are an integral part of the microcirculatory network. Capillaries form a network around organ tissues. Blood circulation through these capillary networks is responsible for nutrient exchange and removal of waste from tissues, an essential process required for a healthy organ function. These capillaries are constantly degenerated and regenerated through a regulated process to ensure optimal functioning. The function of IGF-1 in our blood circulation is to keep regenerating new capillaries and to maintain the health of the existing capillaries, subsequently, contributing significantly to organ health and function
Decreased IGF-1 levels are associated with compromised
microcirculation, which affects brain health and function.
A study carried out in Sweden established a link between
the microvasculature of the brain and decline in memory
associated with ageing. The study showed elderly people
experienced higher blood pressure surges in their brains due to stiffening of the large arteries which can lead to capillary damage. This capillary damage can result in an under-supply of oxygen and nutrients to surrounding brain cells and ultimately result in cell death. This was further correlated to reduced brain volume in areas responsible for memory and cognition. Thus, highlighting the critical role of microcirculation and capillary health in preserving memory and normal cognitive function, especially with age.
cGP and IGF-1: The dream team
The functionality of IGF-1 in the body is limited because about 95% of it is bound to a protein that inactivates it. When unbound from this protein, IGF-1 is freely available to bind to its receptors, which ‘activate’ it allowing the execution of its functions. Scientists have been searching for ways to increase IGF-1 levels for years. However, IGF-1 cannot be increased by direct administration due to its poor uptake and rapid inactivation in the central nervous system.
cGP therefore becomes an important piece of the puzzle. cGP is produced endogenously and sophisticated studies have shown that cGP binds to the protein that normally inactivates IGF-1. The upshot is that cGP frees up IGF-1, meaning more IGF-1 in
the bloodstream.
In vitro and in vivo models confirmed that cGP maintains homeostasis by stimulating IGF-1 function when it is insufficient or inhibiting IGF-1 function when it is overactive. In order to preserve IGF-1 function, which declines with age, the body produces more cGP. An overall well-being is maintained if the body is able to produce sufficient cGP to meet these
demands. However, if the body is unable to produce enough cGP to meet these demands, we start to experience discomfort and develop age-related symptoms such as cognitive decline, poor sleep, mental fatigue, irritability, anxiety and an overall reduced quality of life. This process begins as early as age 45 and can be even earlier if you live a stressful lifestyle or have a lifestyle disease such as metabolic syndrome. The body’s requirement for cGP increases even more with age, while its ability to produce cGP unfortunately decreases, creating a deficit. This results in worsening symptoms and contributing to age-related vascular diseases. Dementia, stroke, Parkinson’s disease, Alzheimer’s disease and hypertension are all vascular diseases that have been associated with low cGP and therefore, low IGF-1 function. Fortunately, exogenous cGP found in various plants, animals and fungi sources can be used to supplement the body’s cGP reserve – a true blessing from mother nature.
Natural cGP
The first identification of natural cGP in NZ-grown blackcurrants, by Dr Jian Guan (CSO, The cGP Lab) and her team of scientists was a game-changer. While conducting a trial in Parkinson’s disease patients, NZ blackcurrant-based capsules were given to them for their anthocyanin content. However, upon further exploration, it was revealed that it was in fact the cGP present in these capsules that reduced their levels of depression and anxiety. The study also showed that the amount of cGP in the cerebrospinal fluid of these patients increased significantly, suggesting its high bioavailability and access to the central nervous system.
This research opened up a unique opportunity and cemented the potential of natural cGP supplementation to support the vasculature, slowing age-related decline and improving overall quality of life. This led to the creation of a product that was the world’s first ever natural cGP supplement by The cGP Lab Ltd. This was then followed by a series of studies that evaluated the role of cGP supplementation in diverse population cohorts spanning across varied health conditions. Through ongoing research and open-label trials, cGP supplementation has shown positive effects on anxiety, depression, peripheral nerve function, blood pressure and glucose metabolism.
The cGP Lab is committed to developing a range of health supplements to support the growing ‘ageing’ market. Their research and development program continues looking into other natural sources of cGP and subsequently, the applications of cGP supplementation. The cGP Lab has just launched a professional range exclusively distributed by FxMed called cGPMax®PLUS.
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