Carnosine and Diabetes

Diabetes Mellitus is a disease in which blood glucose or blood sugar levels are too high. Glucose comes from the foods we eat. Insulin is a hormone that helps the glucose get into the cells to give them energy. With type 1 diabetes, the body does not make insulin. With type 2 diabetes, the more common type, the human body does not make or use insulin well. Without enough insulin, glucose stays in the blood. Diabetes mellitus is not a single disorder, it represents a series of metabolic conditions associated with hyperglycaemia and caused by defects in insulin secretion and/or insulin action. Exposure to chronic hyperglycaemia may result in microvascular complications in the retina, kidney or peripheral nervous system.

Studies show that people who are diabetic or pre-diabetic have low concentrations (63% below normal) of Carnosine in their muscle and brain cells. Obese individuals who were given L-carnosine demonstrate a decrease in their blood sugar levels.

Oxidative stress has been identified as a common mechanism for cellular damage and dysfunction in a wide variety of diseases, including diabetes (Giacco & Brownlee, 2010; Miceli, Pampalone, Frazziano, Grasso, Rizzarelli, Ricordi & Conaldi, 2018). Current understanding of the metabolic changes associated with the development of insulin resistance has focused on the role of oxidative stress and its interaction with inflammatory processes at both levels: the tissue and organism level. Obesity-related oxidative stress is an important contributing factor in the development of insulin resistance in the adipocyte as well as the myocyte. Moreover, oxidative stress has been linked to mitochondrial dysfunction, and this is thought to play a role in the metabolic defects associated with oxidative stress. Of the various effects of oxidative stress, protein carbonylation has been identified as a potential mechanism underlying mitochondrial dysfunction. Karnozin Extra is a dietary supplement that protects cells from oxidative stress with different mechanisms, including its anti-oxidant and anti-carbonylating effect on the mitochondrial level.

There is no doubt that all diabetics are familiar with HbA1c. This is glycosylated haemoglobin, which provides information on the level of glucose in the blood over the last few months. Latest studies show that the most important effect of carnosine probably is an anti-glycation effect (Houjeghani, Kheirouri, Faraji, & Jafarabadi, 2018).

Diabetes intensifies the process of glycation, which is one of the reasons (but not the only one) that diabetics’ arteries are susceptible to thickening of the walls and furthermore to the development of atherosclerosis. The occurrence of atherosclerosis in diabetic patients is three times higher than in those who do not suffer from this disease, as well as the incidence of myocardial infarction and cerebrovascular disorders.

L-carnosine controls the blood sugar level by means of H3- receptors of the autonomic (vegetative) nerves system. Tests on animals have shown that pregnant mice with a lack of carnosine have a much greater chance of giving birth to offspring with diabetes. This is explained by the effect of carnosine that improves glucose tolerance in the foetus. In this way, carnosine may be important for mothers with diabetes, as it reduces the risk that their children suffer from this disease.

The carnosine supplementation protects humans against diabetic nephropathy. Studies conducted on rats by a team of Japanese scientists showed the possibility of using L-carnosine to lower blood glucose levels by regulating the activities of autonomic nerves. L-carnosine has an anti-glycation effect and inhibits secondary complications associated with diabetes.

As well as stabilizing blood sugars in diabetics, Carnosine also protects against many complications of diabetes, such as organ failure, hearing loss, osteoporosis,  eye problems, heart damage and more. People with diabetes often have peripheral neuropathy – a condition where the nerves in the body’s extremities (hands, feet, and arms) are damaged. Carnosine can prevent pain associated with this condition.

L-carnosine is suitable for all types of diabetes, as it reduces the risk of developing complications of diabetes, such as heart and cerebrovascular disease, atherosclerosis, kidney and eye complications (Kianpour & Yousefi, 2019)

What is glycation (non-enzymatic glycosylation)?

A process called glycation (glycosylation) takes place every second throughout our body. This reaction can be described as the binding of protein molecules to molecules of sugar (glucose), and it is followed by the creation of damaged, non-functional structures. This process of glycation changes the structure of the proteins and reduces the biological activity of the same. Glycation proteins accumulated in the affected tissues are clear indicators of the disorder. Many diseases that are associated with ageing, such as diabetes, atherosclerosis, cataract and some neurological diseases, can at least be attributed to glycation.

L-carnosine prevents glycation and plays an important role in the removal of glycation proteins. The so-called carnozinilation – the process of setting the carnosine for denatured molecules, allows the removal of glycation of proteins from cells.

Glycation, known in biochemistry as Maillard’s reaction between protein and glucose, is considered an important factor in ageing, complications caused by diabetes, and probably in malignant tumours. Glucose is the “food” for glycation, malicious binding of protein/glucose is accompanied by the formation of free radicals, leading to “AGEs” (Advanced Glycation End-products). When “AGEs” form, they interact with neighbouring proteins and form pathological crucial bonds (cross-links), which cause hardening and stiffness of tissue. It is the subject of the current debate that actually no other molecule has such an important and potentially toxic effect on the proteins as “AGEs”. Diabetics build a huge amount of “AGEs”, a significantly earlier in life compared to healthy persons, and this process completely disturbs organs whose functioning depends on flexibility. It is proven, that glycation processes alone lead to a “hardening” of the arteries in diabetics. “AGEs” launches a series of destructive processes when it binds to the associated cell structures. One of the results is making 50 times more free radicals. Therefore, diabetes is actually a disease of accelerated ageing and source for “AGEs,” in this case in particularly affected arteries, the lens of the eye and the retina, peripheral nerves and kidneys. Preventing glycation means that damages accompanied by inflammatory and degenerative changes are alleviated. The rats with diabetes, untreated by glycation inhibitors, show twice as heavy damages of kidney glomeruli caused by the “AGEs”, compared with a control group that was treated by these inhibitors.

Supplementation by glycation inhibitors may enable the prevention of many deviations that accompany the ageing process. Given the fact that carnosine structurally includes the places that glycation attacks, carnosine must be sacrificed in order to protect their goal. Carnosine also supports proteolytic pathways, removal of damaged, unnecessary and often harmful proteins (Menini, Iacobini, Fantauzzi & Pugliese, 2020). .

Therefore, L-carnosine with its anti-glycation effect is useful in the prevention and treatment of complications caused by diabetes, such as cataract, neuropathy, arteriosclerosis and kidney failure.

Researcher J. Vinson (University of Granton, PA, USA) studied the ability of carnosine to inhibit protein glycation and AGE’s formation. The results of this study showed that carnosine is indeed an important antioxidant in vivo. Although the mechanism of the inhibition is still obscure, carnosine was shown to be antioxidant and/or bind to sugars. As a result, the formation of both AGE’s and Amadory’s products is inhibited. Vinson suggested that carnosine can be used as a drug for decreasing the glycation rate in cells.

Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation research107(9), 1058-1070.

Miceli, V., Pampalone, M., Frazziano, G., Grasso, G., Rizzarelli, E., Ricordi, C., … & Conaldi, P. G. (2018). Carnosine protects pancreatic beta cells and islets against oxidative stress damage. Molecular and cellular endocrinology474, 105-118.

Houjeghani, S., Kheirouri, S., Faraji, E., & Jafarabadi, M. A. (2018). L-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor–α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial. Nutrition Research49, 96-106.

Kianpour, M., & Yousefi, R. (2019). Carnosine Prevents Different Structural Damages Induced by Methylglyoxal in Lens Crystallins. Cell biochemistry and biophysics77(4), 343-355.

Menini, S., Iacobini, C., Fantauzzi, C. B., & Pugliese, G. (2020). L-carnosine and its derivatives as new therapeutic agents for the prevention and treatment of vascular complications of diabetes. Current medicinal chemistry27(11), 1744-1763.