Actovegin: Therapeutic Power in Modern Medicine

Actovegin, a unique calf blood extract, is distinguished by its ability to increase the efficiency of our cells' oxygen utilisation and better assimilation of nutrients. This process naturally increases blood flow to our brain. Why is this important? Because increased blood flow means that our brain receives more energy, which can improve our memory.

Actovegin is produced from calf's blood by a special filtering process that captures small beneficial chemical compounds. It contains ingredients smaller than 5,000 Da. People use actovegin for a variety of brain-related problems, such as memory deficits, injuries and even complications from diabetes.

But how exactly does actovegin work? At its core, it works by stimulating our cells to use and produce energy more efficiently. It also helps our brain to absorb glucose, a key source of energy, more efficiently. This unique ability has sparked discussion about its potential impact on overall performance.

The standout ingredient in actovegin is inositol-phosphoryl-oligosaccharides (IFOs). These ingredients play a key role in the transport of glucose into our brains. In addition, they can penetrate the protective barrier around our brain and stimulate important enzymes responsible for glucose processing.

In this article we will discuss actovegin in detail, seeking to reveal its benefits, uses and the scientific basis that makes it so effective.

Health benefits of actovegin supported by medical studies

Research has investigated the potential of actovegin in the management and prevention of various medical conditions. The following health effects are reported in various clinical trials and scientific studies.

Actovegin for Diabetes Patients

Actovegin appears to have many benefits for patients with diabetes, from improving insulin response to aiding recovery from serious illness and even potentially preventing nerve damage.

Actovegin offers a glimmer of hope for patients with diabetes, and recent studies have explored its potential benefits. One significant study involving 567 patients with diabetes examined the effects of actovegin on nerve pain. For 160 days, patients received treatment in the form of drips, followed by tablets. The results were promising: those treated with actovegin reported a reduction in nerve pain, increased foot sensitivity and an overall improvement in wellbeing, all without significant side effects [1]. Further studies cemented actovegin's reputation as a potential breakthrough in the treatment of nerve pain in diabetics. For six months, patients with diabetes were given either actovegin or a placebo. The results showed a clear advantage for those taking actovegin, with marked improvements in pain relief. However, it was noted that patients taking certain blood pressure medications may not experience as much benefit [2].

In addition to nerve pain relief, actovegin has shown potential in another key aspect of diabetes - blood sugar control. In a separate study with 40 participants (half of whom were diabetic), actovegin was administered for 14 days. Amazingly, the diabetic patients showed improved blood sugar control without any change in insulin levels [3].

Additionally, one study investigated the role of actovegin in wound care in diabetics. A cream containing human epidermal growth factor, combined with actovegin, was tested on diabetic foot ulcers in a group of 61 patients. Those who used the cream with the higher concentration of growth factor experienced up to 95% healing rate in just 12 weeks, highlighting the potential of actovegin to accelerate healing of foot ulcers in diabetics [4].

Improving insulin sensitivity in type II diabetes: actovegin, produced from calf's blood, was studied for its effect on improving our body's response to insulin in people with type II diabetes. When administered as daily drips (actovegin 2000 pro infusions, 500 ml per day) for 10 days, the treatment increased the body's sugar utilisation by as much as 80% without changing insulin levels. Although we do not fully understand how this works, there is speculation that actovegin may provide special compounds (called IPOs) that can help cells better assimilate sugar [5].

Accelerating recovery from ketoacidosis in type 1 diabetes: ketoacidosis is a serious condition in which the body's blood becomes too acidic. When actovegin was used together with another drug called reamberin, it helped patients return to consciousness and thinking faster. In fact, with this combination, people regained consciousness in just about 19.2 hours. What's more, they had better thinking skills that lasted up to 28 days after their crisis [6].

Help with diabetic neuropathy: Around a third of diabetics suffer from nerve damage called neuropathy. In a study on rats with diabetic symptoms, actovegin improved nerve function and even reduced damage. It particularly helped when given in higher doses, and perhaps acts by calming harmful reactions in nerve cells [7].

Treatment of leg problems and diabetic foot complaints: In a study involving 200 patients with blood flow problems in the legs and diabetic foot disease, actovegin showed promising results. Some patients received actovegin before surgery, such as angioplasty, while others had it as their main treatment. In both cases, it worked well and was cost-effective. Depending on the severity of the condition, patients received different doses, either as injections or as tablets [8].

Based on these results, actovegin presents a promising pathway for the treatment and management of diabetes and its associated complications. Its multifaceted benefits include increasing insulin sensitivity in type II diabetics, aiding recovery from diabetic crises and reducing nerve damage. These results highlight the potential of actovegin as a versatile therapeutic agent in the spectrum of diabetes care.

Actovegin in ulcer care

Actovegin shows a potential role in ulcer management, especially for those with complicating factors such as ischaemic heart disease or diabetes. A study involving 194 patients found that those who were treated with actovegin experienced faster ulcer healing and also enjoyed longer recurrence-free periods [9]. This suggests that actovegin could be a beneficial treatment option in both inpatient and outpatient settings.

Effect of actovegin on gastroduodenal ulcers: In a separate study on refractory gastroduodenal ulcers (located in the stomach and initial part of the small intestine), the combination of actovegin with a technique called intraluminal laser blood irradiation (ILBI) showed particularly promising results. Patients undergoing this combined treatment experienced noticeable pain relief, reduced inflammation and improved gastric mucosal health.

Additionally, beneficial changes in gastric mucus composition have been noted, suggesting increased healing and metabolic activity of the gastric and intestinal mucosa. It appears that this combination not only aids in the physical healing process, but may also bring balance to certain regulatory substances in the body, providing effective treatment for refractory ulcers [10].

Benefits of actovegin for brain and nervous system health:

Actovegin is a substance derived from calf blood and shows significant potential for supporting and improving brain and nervous system health, especially in cases of chronic brain anaemia and age-related memory impairment.

Enhancing Thinking Ability after Stroke: After a stroke, returning to normal mental functioning can be a challenge. A study on older people who had recently experienced a stroke showed that actovegin could be a solution. Participants in the study were treated with actovegin, initially through an intravenous (IV) drip and then in pill form, for six months. The results revealed that those taking actovegin noticeably improved their performance on cognitive tests compared to the placebo group [11].

Promising Results for Brain Health in Older People: Older people, especially those with brain problems affecting memory and attention, may benefit from actovegin. In a study of 60 such individuals, those who took actovegin experienced significant improvements in mental performance. Importantly, 70% of those treated with actovegin felt significantly better, compared to only 35% in the placebo group [12].

Improving Memory and Reducing Thinking Problems: Ageing sometimes brings early signs of memory and thinking problems. In one study, actovegin was given as daily injections to older people showing early signs of such problems. Results showed faster thinking, fewer memory problems and fewer feelings of sadness or fatigue [13].

Improving Overall Wellbeing in Older People: For seniors, especially those with heart or brain-related health problems, actovegin pills may offer potential health benefits. When given to 70 elderly patients for six weeks, many reported improvements in memory, energy levels, sleep quality and overall strength [14].

Protection of Neurons and Reduction of Cell Damage: At the cellular level, actovegin also demonstrated its power. In a study on rat neurons (cells crucial for brain function), exposure to actovegin increased cell numbers and connections. Furthermore, it showed properties to reduce potential cellular damage and act against harmful oxidative agents [15].

Support of the Antioxidant Brain System: In an experiment on rats with chronic cerebral anaemia, administration of actovegin (5 ml/kg) played a key role in restoring the brain's antioxidant system. This included normalisation of glutathione levels, restoration of the activity of a protective enzyme called superoxide dismutase (SOD) and reduction of harmful malondialdehyde (MDA) concentrations [16].

Improved Cognitive Function and Blood Flow: In a human study focusing on people with chronic cerebrovascular pathologies, up to 81% patients treated with actovegin showed improvements in overall health and symptoms. Actovegin showed benefits in improving cognitive function, and results varied according to dose [17].

Supporting Brain Activity and Cognitive Function: For older people, actovegin has been shown to be particularly beneficial for brain activity and cognitive function. In a placebo-controlled study involving people with a mean age of 65 years, actovegin increased alpha and beta brain activity, indicating improvements in brain function and attention [18].

Improving Memory Disorders: Older adults with memory problems may find comfort in the potential benefits of actovegin. Studies indicate that actovegin produces positive changes in brain activity, particularly in regions associated with memory and attention [19].

Support in Ageing Associated with Memory Impairment: In another study targeting patients with ageing associated with memory impairment, actovegin improved and supported cognitive performance. Patients taking actovegin experienced a noticeable increase in brain activity, particularly in the parietal cortex, which is important because reduced activity in this region is often observed in patients with dementia [20].

Based on these findings, actovegin appears to have a number of beneficial effects on brain and nervous system health, offering hope for those with ischaemic disease, memory impairment and other cerebrovascular problems.

Brain Injury Treatment Aid: A study of 68 brain injury patients showed that those who received actovegin (32 out of 68) experienced accelerated recovery. actovegin, administered as an IV of 400 mg per 200 ml mixed with a stock solution for 10 days, accelerated the recovery of lost brain function, reducing overall healing time. Additionally, these patients experienced significant relief of fatigue symptoms and showed improvement in EEG studies, suggesting improved brain activity [21].

Improvement in Chronic Brain Anaemia: Chronic cerebral anaemia can cause energy deficits in the brain, especially in stages I-II, often associated with hypertension or cerebral atherosclerosis. A study comparing actovegin and Mexidol showed that patients treated with both drugs had fewer clinical symptoms associated with the disease, improved cognitive brain function and a significant reduction in subjective symptoms of the disease. It is worth noting, however, that Mexidol had a unique advantage in addressing metabolic energy deficits [22].

Alleviating Cognitive Impairment in COVID-19: actovegin appears promising for treating the endothelial dysfunction seen in patients with COVID-19, which can lead to multiple organ failure and increase the risk of cognitive impairment. Actovegin not only enhances endothelial function and microcirculation, but also shows potential benefits in improving cognitive function, making it a potentially effective therapeutic option for patients with neurological or cognitive impairment caused by COVID-19 [23].

Increasing Cognitive Resources in Association with Age-Related Memory Impairment: A study evaluating the effects of actovegin on event-related potentials associated with cognitive function in patients with age-related memory impairment showed significant results. Patients receiving actovegin showed an increase in P300 amplitude, suggesting increased cognitive processing resources. This increase of up to 4.8 microV, especially in the central and parietal brain regions, was significant and indicates that actovegin may benefit certain aspects of cognitive function in patients with age-related memory problems [24].

Role in Ischaemic Stroke Treatment: Ischaemic stroke can dramatically affect neurological and cognitive function. In a study comparing the effects of actovegin and piracetam on patients with mild to moderate ischaemic stroke, actovegin showed a clear advantage. Patients treated with actovegin experienced significant improvements in general brain symptoms and specific neurological signs. At the end of the treatment period, recovery rates, both in terms of total ischaemic scores and cognitive function, were significantly higher in the actovegin-treated group, making it a powerful choice for the treatment of ischaemic stroke in its acute phase [25].

Protection from Hypoxia: A study involving 12 healthy young men investigated how actovegin affects the brain during hypoxia, a condition characterised by low oxygen levels. The drug is designed to increase the transport of glucose and oxygen into cells. When participants were exposed to hypoxic conditions, measurements showed that certain signals in the brain, known as VEP-P2 and ERG-b-wave, tended to decrease. However, with actovegin treatment, these decreases were corrected, suggesting that the drug may protect central neuronal and perhaps even glial structures from the effects of hypoxia. Furthermore, the infusion method, which introduces a higher dose of actovegin, has been shown to be more effective against the effects of hypoxia [26].

Enhancement of Learning and Memory Processes after Ischaemia: In an experiment on rats that experienced cerebral ischaemia, actovegin showed neuroprotective effects. The drug was administered to these rats and their learning and memory abilities were assessed using the Morris water maze test. The results were promising: rats treated with actovegin showed faster learning and better memory retention. Furthermore, microscopic examination of their brains showed that there was greater cell survival in a key region associated with memory, called the hippocampal CA1 region [27].

Improved Lipid Profile in Hypertensive Patients: In patients with chronic cerebral anaemia and hypertension, actovegin, in combination with ceretone, effectively corrected abnormalities in the lipid profile, which is crucial for erythrocyte membrane stability and structure. This combination therapy significantly outperformed other drug combinations [28].

Increased Cerebral Blood Flow in Metabolic Syndrome: A study on patients suffering from metabolic syndrome showed that combining actovegin with the drug bisoprolol significantly increases cerebral blood flow, even more than with bisoprolol alone. Increased blood flow to the brain is crucial for its proper functioning and health [29].

Promising Treatment for Cerebral Circulatory Failure: In patients showing early signs of cerebral circulation problems, actovegin, in combination with Corinfar, showed significant improvement. The combination therapy appeared to normalise most parameters related to microcirculation and blood rheology, suggesting its potential as a treatment option for patients with cerebral circulation problems [30].

This research supports the potential of actovegin to protect brain health and improve cerebral circulation.

Treatment of dyssyrrhagic encephalopathy in hypertension: In a study involving 56 patients with a diagnosis of dyssyrrculatory encephalopathy due to hypertension, treatment with both actovegin and Captopril resulted in positive clinical outcomes. The results strongly suggest a potential benefit of using actovegin in combination with Captopril to treat such conditions [31].

Improving microcirculation in the limbs: Distal lower limb occlusion is a serious medical problem. In a study involving 60 patients with critical limb ischaemia, those treated with actovegin experienced a significant 35 per cent improvement in skin perfusion by day 15. Furthermore, there was a 12.8 per cent increase in microcirculation, which increased tissue oxygenation. This shows that actovegin may play a key role in improving blood flow in patients with distal limb occlusion [32].

Comparison with solcoseril: In a study to compare the effects of actovegin and solcoseril on the microcirculation in the lower ischaemic limbs, it was found that both treatments had a positive effect on the formation of new capillaries. However, actovegin stood out in particular, showing better results in improving microcirculatory dynamics and promoting a denser capillary network [33].

Supporting recovery after stroke: In a study involving 104 patients with acute ischaemic carotid artery stroke, those who received 250 ml of actovegin daily showed significant improvements in neurological progress and functional recovery by day 30, compared to the control group. The level of statistical significance was recorded as p < 0.005. This indicates that actovegin has the potential to significantly enhance post-stroke recovery without causing negative side effects [34].

Reduced risk of stroke in patients with chronic cerebral anaemia: Patients with chronic cerebral anaemia are at risk of experiencing a stroke within 10 years. A study involving 54 patients highlighted that those with vertebrobasilar anaemia are at particular risk. However, actovegin showed impressive therapeutic effects on autonomic nervous systems. The study further revealed actovegin's ability to affect blood vessel walls through various pathways, which in turn showed promising hypotensive effects. This suggests that actovegin may reduce the long-term risk of stroke in such patients [35].

Based on these results, actovegin presents itself as a versatile drug with potential benefits in the treatment of a variety of medical conditions, from improving microcirculation in the limbs, to supporting post-stroke recovery, to reducing long-term stroke risk.

Neuroprotective properties after ischaemic stroke: A study in rats showed that after experiencing an ischaemic stroke, a dose of decongested calf serum (actovegin/Solcoseryl) significantly reduced the neurological damage and volume of the affected brain within 24 hours. This is particularly striking compared to rats that did not receive this treatment (with statistical significance p < 0.0005). The serum acts by counteracting the negative effects of hypoxia-glucose on nerve cells, reducing harmful forms of reactive oxygen species and preventing cell death. The result is less cell damage and better survival rates for these cells [36].

Improved treatment for carotid artery ischaemia: A study involving 25 patients with moderate carotid artery ischaemic stroke demonstrated the potential benefits of actovegin. In combination with other neuroprotective agents, the treatment led to noticeable improvements in patient recovery. In just 21 days, patients on this combined treatment experienced reduced neurological deficits, better overall functional recovery and reduced inflammatory indices compared to those on standard care [37].

Enhancing antidepressant treatment for the elderly: In elderly patients diagnosed with mild to moderate depression, actovegin was investigated as a potential addition to a new generation of antidepressants. The study showed that adding actovegin to standard antidepressant treatment resulted in faster and more pronounced therapeutic effects. By week 4, patients on the combined therapy showed significant reductions in depressive symptoms, improvements in cognitive function and higher rates of positive responses. This suggests that actovegin may help to accelerate recovery and potentially even reduce the length of hospital stay for older patients [38].

Best combination for chronic cerebral ischaemia: When evaluating different drug combinations for the treatment of chronic cerebral ischaemia, the combination of actovegin and Cereton proved to be the most effective, suggesting that this combination may offer optimal therapeutic outcomes [39].

Post-stroke rehabilitation: actovegin was highlighted in a large study involving 1,920 post-stroke patients. The study showed that among several drugs tailored for patients after ischaemic stroke, actovegin stood out as one of the most effective. Moreover, for patients recovering from haemorrhagic stroke, actovegin was the only drug that had a positive effect on rehabilitation [40].

Based on these results, actovegin appears to offer multiple benefits in a variety of medical scenarios, from improving recovery after stroke to enhancing the effectiveness of antidepressants in the elderly. The aforementioned studies provide significant evidence of its therapeutic potential, making it an exciting area for further research.

Recovery from post-operative stroke: Following surgery for acute abdominal conditions, some patients may develop acute cerebrovascular disorders. These disorders can range from transient ischaemic attacks, acute hypertensive encephalopathy to various types of stroke. Interestingly, as many as 86.9% of these disorders occur within the first three days after surgery. Actovegin, especially when administered within the first 24 hours after surgery, shows the potential to accelerate recovery from these neurological deficits. This treatment not only promotes faster recovery, but also helps to improve cerebral blood flow in patients who have suffered postoperative strokes [41].

Neuroprotective role in cerebral ischaemia: Cerebral ischaemia refers to a lack of blood supply to the brain, which can lead to brain damage or stroke. In experiments in rodent models that mimicked conditions of both sudden and gradual reduction in blood supply to the brain, actovegin proved beneficial. In particular, it assisted in the recovery of neurological function and reduced the negative effects of sensory, motor and cognitive impairment in rats [42].

Inhibitory effect on harmful oxygen radicals: Oxidative stress, which includes the production of harmful oxygen radicals, plays a role in many chronic diseases. Patients with heart failure may have an increase in these harmful radicals. Actovegin reduces the formation of these radicals. In some cases, even a low dose of less than 1 mg/mL was sufficient to see this inhibitory effect. Furthermore, when human neuroblastoma cells (a model for nerve cells) were exposed to hydrogen peroxide, a substance that can lead to cell death, pretreatment with actovegin noticeably reduced this cell death. It is thought that actovegin may act not only by reducing certain harmful substances, but also by neutralising the effects of other highly reactive molecules in the cells. These findings highlight the potential role of actovegin in reducing the chronic inflammation often associated with heart failure and its protective effects on the central nervous system [43].

In conclusion, actovegin presents itself as an exciting avenue for medical treatment. From promoting recovery from post-operative strokes, to playing a neuroprotective role, to counteracting harmful radicals, its therapeutic benefits, as demonstrated by various studies, make it a noteworthy agent in medical science.

Benefits of actovegin for physical health, mobility and muscle recovery

Actovegin has shown promising results in improving physical mobility, especially in patients suffering from peripheral arterial disease (PAD) and those undergoing physiotherapy.

Improvement in patients with PAD: A study involving participants from Russia, Georgia and Kazakhstan aimed to assess the efficacy of actovegin in the treatment of PAD [44]. Participants underwent an initial two-week intravenous treatment with actovegin, followed by a 10-week oral treatment. By week 12, there was an almost 29% improvement in the distance participants could walk without experiencing pain. This progression was over 35% at the end of week 24, meaning that participants could walk an additional 41 metres without discomfort. In addition, their overall walking ability increased by 36%. Furthermore, those treated with actovegin reported a better quality of life according to the SF-36 Mental Health Scale. This study also confirmed that actovegin has minimal side effects, confirming its safety [44].

Improved physiotherapy outcomes: The addition of actovegin to standard physiotherapy procedures resulted in improved mobility outcomes. In a study involving 105 patients, intravenous administration of actovegin together with baseline physiotherapy led to 12% improvement in walking ability compared with the placebo group [45]. This implies that actovegin may enhance the benefits of regular physiotherapy, offering patients improved mobility and physical independence.

Increased walking ability in patients undergoing physiotherapy: In another study, the researchers focused on 105 participants undergoing physiotherapy. Those treated with intravenous actovegin increased their walking ability by 12% more than those who received placebo, reinforcing the notion that actovegin can increase the effectiveness of physiotherapy [46]. Importantly, both groups responded well to baseline physiotherapy, indicating that actovegin is a potential enhancer and not the only treatment.

Thus, these studies indicate that actovegin has potential as an additional treatment in improving physical health, mobility and muscle recovery. For those with PAD or undergoing physiotherapy, it offers hope for increased mobility and a better quality of life.

Benefits of actovegin for Muscle Regeneration and Strengthening (in sports/athletes)

Actovegin has shown impressive results in promoting muscle recovery and stimulating cellular growth. In a study with 103 participants, those with muscle injuries received injections of actovegin directly into the injured area, at intervals of several days. The results were impressive. The recovery time for those treated with actovegin was about 5.5 weeks, almost three weeks shorter than for those who received a placebo. This means that athletes or anyone suffering from a muscle injury can get back in shape almost three weeks earlier than with traditional treatments, which could be a breakthrough for those involved in competitive sports [47].

In addition to helping with regeneration, actovegin also appears to play a key role at the cellular level. When muscle cells, specifically C2C12 myoblasts, were treated with actovegin, a significant improvement in their growth was observed. Important markers of cell growth, such as Ki67 and myosin heavy chains, increased significantly in the presence of actovegin, indicating increased proliferation of muscle cells. This study suggests that actovegin may contain components that are beneficial to muscle cells and may help them grow more efficiently [48].

Exploring actovegin's potential to enhance physical performance, another study examined its effects on human skeletal muscles. The results revealed that actovegin improved the ability of mitochondria in muscle cells to respire. It increased the ability of muscles to use oxygen for energy production. These results support the potential of actovegin as a possible performance enhancer for individuals (athletes) wishing to increase their physical abilities. Although further research is required, these results may have implications for its use in sport [49].

Furthermore, in a competitive sports environment, another study highlights the advantages of combined treatment. Actovegin combined with the homeopathic drug Tr14 can significantly accelerate muscle recovery. The combined treatment appeared to favour the expression of genes and proteins that promote muscle growth, leading to faster recovery from injury. For athletes, this can mean a faster return to the field after suffering a muscle injury [50].

Based on these results, actovegin, alone or in combination with other treatments, shows promising potential in accelerating muscle recovery, promoting cell growth and the possibility of even enhancing athletic performance. Its benefits are evident in various studies, making it a valuable component in sports medicine and rehabilitation.

Effects of actovegin on Oxygen Metabolism and Utilisation

Actovegin, mainly known for its metabolic and neuroprotective properties, has shown a significant impact on the way our body uses oxygen.

The study showed that actovegin indirectly improves the efficiency of oxygen utilisation in tissues. Specifically, it increases the amount of oxygen that red blood cells (erythrocytes) can carry [51]. This unique property allows actovegin to act as an anti-hypoxia agent, which is particularly helpful for patients experiencing acute gastric distress [51]. In another study, actovegin significantly improved the entire process of oxygen management in the body, further highlighting its ability to counteract hypoxia [52].

In pregnant women experiencing complications such as impaired umbilical cord blood flow or placental circulation leading to fetal hypoxia (insufficient oxygen supply to the fetus), actovegin in combination with 5% glucose and vitamin C showed promising results. The solution administered by drip was effective in treating fetal hypoxia in a significant number of test cases, thus preventing possible complications at birth. The role of actovegin here was mainly to modify metabolic processes and protect key areas from the negative effects of oxygen deficiency [53].

Furthermore, in an experiment with healthy volunteers, actovegin demonstrated an effect on the relationship between metabolic activities and microcirculatory processes in the skin. Significant changes were observed in several parameters, such as 98% increase in endothelial rhythm amplitude, indicating a link between metabolic processes and microhaemodynamics in the skin [54].

In stressful situations, as in the study in which the rats experienced prolonged immobilisation stress, the periodontal soft and hard tissues (parts of the gums and teeth) showed a decrease in oxygen levels and metabolism. However, the introduction of actovegin (together with Thiotriazolin) helped to offset these stress effects by maintaining oxygen balance in these tissues [55].

All of these results point to the promising potential of actovegin in a variety of medical scenarios, particularly in relation to oxygen utilisation and metabolism. Whether it's athletes in need of faster recovery, high-risk pregnancies or those experiencing acute medical problems, actovegin's ability to improve oxygen utilisation may be the solution many are looking for.

Benefits of actovegin for eye health

Actovegin has shown promising potential in improving the health of our eyes, especially in conditions related to vision problems caused by various causes.

In a study targeting older people with retinal problems caused by high blood pressure, the addition of actovegin to standard treatment for hypertension produced encouraging results. Specifically, 36% elderly participants noticed not only improvements in vision, but also increased wellbeing and quality of life [56].

In another innovative approach, the researchers investigated a new method of delivering drugs directly into the vascular system of the eye. Using this method, they administered actovegin and trental to a group of patients suffering from visual problems related to nerve damage in the eye. The results were quite impressive - the patients' visual acuity increased significantly, from low scores of 0.03-0.06 to much sharper scores of 0.3-0.8. In addition, some of the eye problems, such as central scotomas, disappeared and the axial conduction of the optic nerve bundle improved significantly [57].

Further evidence suggests that actovegin may also play a role in the treatment of a specific ocular condition known as optic nerve neuropathy in glaucoma, particularly in patients with open-angle glaucoma (POAG) occurring together with myopia. The group of participants, all with a diagnosis of POAG and high myopia, were treated with a protocol that included actovegin among other drugs. The treatment was designed to address a variety of issues, from blood flow dynamics to metabolic shifts, affecting the progression of glaucoma in people with myopia [58].

These results indicate that the benefits of actovegin for eye health are manifold and continue to be explored in a variety of contexts, from improving visual acuity in the elderly, to innovative drug delivery for increased visual acuity, to treating specific eye conditions.

Benefits of actovegin for skin health

Actovegin has also shown promising benefits for skin health.

In one study, researchers investigated how actovegin affects blood flow and metabolism in the skin. Twenty-eight volunteers were given actovegin intravenously, and then blood flow in the skin of the forearm was measured using advanced instruments, and fine blood vessels in the nail were observed. The results showed that actovegin not only improved blood flow in the skin, but also increased the overall metabolic activity of the skin cells. This means that skin cells were more active and healthier after actovegin administration. Furthermore, it was noted that it led to better vasomotion (movement of blood vessels) in different rhythms, which can be interpreted as better skin health at the micro level [59].

Another interesting aspect of actovegin's potential benefits for skin health is its radioprotective properties. Actovegin appears to provide a protective shield for skin cells when they are exposed to harmful radiation. In a specific experiment, human skin cells were exposed to a dose of X-rays, resulting in a significant decrease in cell numbers. However, when these cells were treated with actovegin, not only did a higher percentage survive the radiation, but their numbers even increased slightly. Even more impressively, using actovegin alone without radiation led to a fivefold increase in cell numbers in just six days! At the molecular level, actovegin was able to reduce the expression of a protein (EGFR) that normally increases when skin cells are exposed to radiation. This suggests that actovegin may counteract some of the damaging effects of radiation on our skin, which is an important finding given the various sources of radiation we are exposed to in today's world [60].

These results indicate that actovegin presents great promise for skin health, from improving blood flow and metabolism in skin cells to protecting against radiation damage.

Benefits of actovegin for digestive health

Actovegin is also presented in scientific studies as a means of protecting and healing the digestive system, particularly against radiation injury.

The study, conducted on Wistar rats, aimed to investigate the effects of radiation on small intestinal mucosal epithelial cells and see how actovegin could help. The researchers irradiated the abdomens of these rats and then treated some of them with different doses of actovegin. In the group exposed to radiation alone, there was a significant increase in levels of IL-2 and IL-6 - indicators of inflammation. However, the rats that received actovegin after irradiation showed significantly better health in their intestinal tissues. Specifically, the structure and thickness of their intestinal layers improved [61].

At the molecular level, actovegin played a role in reducing harmful proteins that cause cell death (apoptosis) and increasing beneficial proteins that prevent apoptosis. Essentially, actovegin has demonstrated its ability to defend intestinal cells against the negative effects of radiation, indicating its potential for treating conditions such as radiation enteritis, a radiation-induced inflammatory bowel disease [61].

In another study, researchers reported that actovegin can help recovery from radiation-induced intestinal damage. After exposure to radiation, some rats received injections of actovegin. The results were consistent with the previous study: those treated with actovegin showed significant improvements in intestinal health. The height of their intestinal villi, the depth of their crypts (small valleys in the intestines) and the overall thickness of the mucosal lining were better. Again, at the cellular level, actovegin was key in balancing proteins that control cell death, promoting intestinal cell survival and health. This study indicates the potential of actovegin to treat radiation-induced intestinal damage [62].

Other health benefits of actovegin

Actovegin has shown many promising benefits in various health studies. Here are some key findings from the scientific studies:

Enhancing neutrophil function after freezing: actovegin can renew neutrophils, a type of white blood cell crucial to the immune response. In a study comparing actovegin with bovine umbilical cord blood fraction, both agents increased the ability of neutrophils to engulf and digest harmful entities after freezing and thawing. Specifically, when exposed to 1.5 mg/ml actovegin, neutrophils showed an improvement in oxygen-related metabolism, which is crucial for their function [63].

Promotion of sperm production after clinical death in rats: male rats that experienced simulated clinical death had a significant decrease in sperm and sperm-associated cell production. However, after a dose of actovegin, the negative effects were negated. Moreover, sperm production returned to normal within 45 days after resuscitation [64].

Benefits for patients with metabolic syndrome: In a study involving patients with metabolic syndrome, a condition associated with an increased risk of heart disease, stroke and diabetes, a combination therapy of actovegin and pancreatic enzymes was used. The combination significantly improved small bowel function, leading to better digestion, absorption and movement of food through the gut. In addition, patients showed lower levels of triglycerides, total cholesterol and other harmful factors [65].

Alleviating symptoms of post-thrombotic disease in the lower limbs: actovegin was investigated for its benefits for patients with post-thrombotic disease, a condition following deep vein thrombosis. Included in the treatment plan, patients reported numerous improvements. This includes significant reductions in ankle swelling, tingling sensation, cramping frequency, pain intensity and overall improvement in quality of life [66].

Improving outcomes for patients undergoing carotid artery surgery: Carotid endarterectomy is a surgical procedure to prevent stroke in patients with significant carotid artery blockages. A group of patients, prior to undergoing this surgery, received actovegin. This 'preconditioning' led to improved cerebral blood flow and better surgical outcomes. Furthermore, significant cognitive improvements were noted in these patients, both one week and six months after surgery [67].

Prevention of clefts in expectant mothers with a history of clefts: Between 1980 and 2005, a group of 71 women with a personal or family history of clefts received a prophylactic regimen that included both vitamin B complex and actovegin, administered twice weekly. As a result, a significant number, 80 out of the total number of births, resulted in healthy babies. The risk of having children with clefts was reduced to 2.9% for cleft lip and palate (CLP) and was 0% for cleft palate (CP), compared to previously known risks of 4.9% for CLP and 2.4% for CP [68].

Improved results of carotid artery surgery: A study on 80 patients with carotid artery problems showed that those who received a daily dose of 1200 mg actovegin for 1.5 months before surgery had better post-operative outcomes. Specifically, they had improved cerebral blood flow, which was observed both seven days and six months after surgery. This treatment also reduced the chances of asymptomatic ischaemic strokes after surgery [69].

Treatment of radiotherapy-induced oral ulcers: actovegin proved effective in the treatment of radiotherapy-induced oral ulcers in patients with cancer. Patients treated with actovegin experienced significantly less pain and had milder oral ulcers after two weeks. In addition, inflammatory markers in the blood were significantly lower than in those treated with other agents [70].

Beneficial for cancer patients undergoing combined treatments: actovegin has been studied in the context of its effects on cancer patients undergoing combined chemotherapy and radiotherapy. One significant side effect of such treatment is painful oral ulcers. Patients who received actovegin from the start of their treatment were significantly less likely to develop severe ulcers. Furthermore, for those who started actovegin after ulcers had developed, there were fewer progressions to severe ulcers [71].

Successful treatment of chronic limb disease: In a study focused on the treatment of chronic limb artery occlusive disease (CODLLA), 80 patients were observed. Half of them were treated with actovegin. After treatment, this group experienced a 56% increase in certain blood flow parameters, indicating improved circulation. In addition, the distance they could walk without pain increased by almost 59% [72].

The results indicate that actovegin has shown a wide range of beneficial effects in a variety of medical contexts, from preventing clefts in expectant mothers, to improving outcomes in surgery, cancer treatments and chronic limb disease.

Mechanism of action of actovegin in various medical conditions

Based on the available data, actovegin shows a complex and multifaceted mechanism of action beneficial for a wide range of medical conditions. In neurology, it shows strong neuroprotective properties. It helps with neural function, pain relief and improved cognitive function, especially in conditions such as type 1 and 2 diabetes and stroke. Laboratory experiments have shown that actovegin promotes neuronal survival and synaptic plasticity and exhibits an anti-apoptotic effect by reducing levels of activated caspase-3.

In addition, actovegin shows significant antioxidant properties. It reduces the production of reactive oxygen species (ROS) and revitalises key antioxidant systems, effectively restoring metabolic balance. In particular, it normalises lactose, pyruvate and glutathione levels and renews the activity of key antioxidant enzymes such as superoxide dismutase (SOD) and catalase. These properties are particularly useful in conditions characterised by oxidative stress and inflammation, such as heart failure.

The compound also plays a role in blood sugar regulation, improving glucose tolerance and insulin sensitivity in patients with type II diabetes. This action may be related to its known effects on improving glucose and oxygen utilisation at the cellular level, crucial for conditions such as ischaemia, where tissue perfusion is limited.

Actovegin also has pronounced effects on wound healing, as it accelerates the healing of ulcers on the feet and duodenal ulcers. It increases the elasticity of erythrocytes and promotes microcirculation, thereby improving blood flow and stimulating the blood supply necessary for the healing of ulcers and ischaemic tissues. Furthermore, actovegin has shown to improve memory, concentration and attention, as demonstrated by increased alpha and beta activity in EEG studies. This is particularly useful for older patients showing signs of cognitive impairment.

In addition, actovegin has shown benefits in accelerating recovery from brain injury and stroke, probably due to its anti-inflammatory and antioxidant effects. In addition, the drug affects lipid profiles, improves both cerebral and peripheral circulation, affects autonomic homeostasis and enhances antidepressant treatment.

How to take actovegin: tablets and injections

actovegin is available in a variety of formulations for different therapeutic requirements. Significantly, the two main forms are tablets and injections. The tablet form provides a convenient oral dosing option, ideal for extended treatment periods or maintenance phases.

The injectable form of actovegin, on the other hand, can be administered both intravenously and intramuscularly, offering rapid action and usefulness for more acute conditions or the initial phases of treatment. These different formulations ensure that actovegin can meet the specific needs of patients in different therapeutic scenarios.

How to dose actovegin in different studies for different conditions

Actovegin, derived from calf blood, has been the subject of various studies, each investigating its potential in different medical contexts. One notable study in type II diabetes mellitus (NIDDM) evaluated the drug's efficacy in improving insulin sensitivity. In this particular study, ten patients with NIDDM received actovegin at a dose of 500 ml per day (actovegin 2,000 pro infusions) for ten days. Another study, focusing on people with chronic lower limb ischaemia and diabetic foot syndrome, evaluated the therapeutic use of actovegin both as an additional treatment for surgical interventions and as a stand-alone method. In severe cases, the drug was administered in doses of 1,000 to 2,000 mg intravenously over 10-15 sessions. Meanwhile, milder cases saw doses between 400-800 mg administered intramuscularly, followed by a switch to a tablet form for continued therapy.

A study targeting older people showing early signs of cognitive problems administered a 5 ml (200 mg) injection of actovegin daily for four weeks. In a separate study that delved into the effects of the drug on people with chronic cerebrovascular pathology and mild cognitive impairment, patients were divided into two groups based on their actovegin doses: either 1,000 mg or 160 mg daily. In the context of traumatic brain injury, another study showed a treatment protocol in which actovegin was administered as a drip, at exactly 400 mg per 200 ml mixed with a standard solution, and treatment continued for 10 days. Finally, in a study of acute carotid ischaemic stroke, patients in one study arm were treated with 250 ml of actovegin daily. These varying doses highlight the diverse uses and therapeutic ranges of actovegin in various medical conditions.

Different doses in different studies for different conditions

• Post-thrombotic disease of the lower limbs:

Dose: intravenous 1200 mg dissolved in saline initially, followed by an oral dose of 1200 mg.

Duration: intravenously for 10 days, then orally daily for 30 days.

• Carotid endarterectomy in patients with chronic cerebrovascular insufficiency:

Dose: 1,200 mg per day.

Duration: 1.5 months before surgery.

• Contingency before carotid endarterectomy:

Dose: 1,200 mg actovegin per day.

Duration: 1.5 months before surgery.

Side effects and precautions for actovegin

Actovegin, like all medicines, can cause side effects, but not everyone will experience them. Some side effects include:

Allergic reactions: this is one of the most serious side effects of actovegin. Symptoms may include skin rash, hives, redness of the skin with a burning sensation and even symptoms of shock. Drug-induced fever is also possible.

Dizziness: some users have reported feeling dizzy after taking actovegin.

Stomach complaints: Particularly after taking higher doses, some people have reported stomach complaints.

Caution in the use of actovegin:

• Allergies: Do not use actovegin if you are hypersensitive to skimmed calf blood serum or to any of the substances contained in the drug.
• Pregnancy and breastfeeding: Consult your doctor before taking actovegin if you are pregnant, think you may be pregnant, are planning a pregnancy or are breastfeeding.
• Interactions with other drugs: According to the available data, no interactions of actovegin with other drugs have been found. However, always inform your doctor about all medications you are taking.
• Dietary restrictions: actovegin tablets should be taken before meals. They contain certain amounts of sodium, potassium and sucrose, which may be important for people on special diets or with certain medical conditions.
• Children: there is a lack of data on the use of actovegin in children. Therefore, its use in this group is not recommended unless prescribed by a doctor.
• Driving and operating machinery: actovegin may have minimal or no effect on the ability to drive and operate machinery. Nevertheless, given that dizziness is a potential side effect, caution is advised.
• Patients with phenylketonuria: actovegin contains phenylalanine, which may be harmful to patients with phenylketonuria.
• Patients with specific dietary restrictions: Due to the sodium and potassium content, those on a sodium or potassium controlled diet should take this into account.
• Overdose: According to the data provided, no cases of actovegin overdose have been reported. Nevertheless, it is always recommended to adhere to the recommended dose and to consult a doctor if an overdose is suspected.

Although actovegin has been shown to be beneficial in a number of conditions, it is important to take the drug as directed and be aware of potential side effects and precautions. Always consult your doctor before starting or stopping any medication.

Summary

Actovegin has demonstrated itself as a versatile therapeutic agent with benefits in numerous areas of medicine. It has shown significant effects in patients with diabetes, aiding in both metabolic and neurological aspects, particularly highlighting its neuroprotective attributes. In addition, its contributions to stroke recovery, sports medicine and the potential to enhance the effects of antidepressants in the elderly population underline its broad applications. Furthermore, its promising potential in eye health and its role in skin protection and restoration confirm its broad therapeutic potential. In short, actovegin's extensive and diverse therapeutic benefits point to its growing importance and potential role in modern medicine.

Disclaimer

This article has been written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest using chemical reagents on humans - this is prohibited by law. For a product to be used for treatment, it must be registered as a medicine. The information contained in the text is based on available scientific research and is not intended as medical advice or to promote self-medication. The reader should consult a qualified health professional for all health and treatment decisions.

References

1. Ziegler, D., Movsesyan, L., Mankovsky, B., Gurieva, I., Abylaiuly, Z., & Strokov, I. (2009). Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes care, 32(8), 1479-1484. https://doi.org/10.2337/dc09-0545 https://pubmed.ncbi.nlm.nih.gov/19470838/
2. Ziegler, D., Edmundson, S., Gurieva, I., Mankovsky, B., Papanas, N., & Strokov, I. (2017). Predictors of response to treatment with actovegin for 6 months in patients with type 2 diabetes and symptomatic polyneuropathy. Journal of diabetes and its complications, 31(7), 1181-1187. https://doi.org/10.1016/j.jdiacomp.2017.03.012 https://www.sciencedirect.com/science/article/pii/S1056872716305086
3. Heidrich, H., Quednau, J., & Schirop, T. (1979). Blutzucker- und Seruminsulinverhalten bei intravenöser Langzeittherapie mit actovegin [Reaction of blood sugar and serum insulin to intravenous longterm treatment with actovegin. Clinical double-blind study (author's transl)]. Medizinische Klinik, 74(7), 242-245. https://pubmed.ncbi.nlm.nih.gov/763217/
4. Tsang, M. W., Wong, W. K., Hung, C. S., Lai, K. M., Tang, W., Cheung, E. Y., Kam, G., Leung, L., Chan, C. W., Chu, C. M., & Lam, E. K. (2003). Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes care, 26(6), 1856-1861. https://doi.org/10.2337/diacare.26.6.1856 https://pubmed.ncbi.nlm.nih.gov/12766123/
5. Jacob, S., Dietze, G. J., Machicao, F., Kuntz, G., & Augustin, H. J. (1996). Improvement of glucose metabolism in patients with type II diabetes after treatment with a haemodialysate. Arzneimittel-Forschung, 46(3), 269-272. https://pubmed.ncbi.nlm.nih.gov/8901147/
6. Kligunenko, E. N., & Sedinkin, V. A. (2011). Eksperimental'naia i klinicheskaia farmakologiia, 74(12), 15-18. https://pubmed.ncbi.nlm.nih.gov/22379876/
7. Dieckmann, A., Kriebel, M., Andriambeloson, E., Ziegler, D., & Elmlinger, M. (2012). Treatment with actovegin® improves sensory nerve function and pathology in streptozotocin-diabetic rats via mechanisms involving inhibition of PARP activation. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 120(3), 132-138. https://doi.org/10.1055/s-0031-1291248 https://pubmed.ncbi.nlm.nih.gov/22020669/
8. Dibirov M. D. (2014). Khirurgia, (2), 33-36. https://pubmed.ncbi.nlm.nih.gov/24736538/
9. Smolianinov A. B. (2000). Lechenie aktoveginom bol'nykh iazvennoĭ bolezn'iu dvenadtsatiperstnoĭ kishki, sochetannoĭ s ishemicheskoĭ bolezn'iu serdtsa i sakharnym diabetom [Actovegin treatment of duodenal ulcer associated with ischemic heart disease and diabetes mellitus]. Klinicheskaia meditsina, 78(6), 24-28. https://pubmed.ncbi.nlm.nih.gov/10900865/
10. Vakhrushev, I.aM., & Shkatova, E. I.u (2003). Otsenka terapevticheskoĭ éffektivnosti sochetannogo primeneniia nizkointensivnogo lazernogo izlucheniia i aktovegina pri trudno rubtsuiushchikhsia iazvakh zheludka i dvenadtsatiperstnoĭ kishki [Therapeutic efficiency of a combined use of low-intensity laser radiation and actovegin in gastroduodenal ulcers with inhibited cicatrix formation]. Terapevticheskii arkhiv, 75(9), 86-89. https://pubmed.ncbi.nlm.nih.gov/14582442/
11. Guekht, A., Skoog, I., Edmundson, S., Zakharov, V., & Korczyn, A. D. (2017). ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind actovegin): A Randomized Controlled Trial to Assess the Efficacy of actovegin in Poststroke Cognitive Impairment. Stroke, 48(5), 1262-1270. https://doi.org/10.1161/STROKEAHA.116.014321 https://pubmed.ncbi.nlm.nih.gov/28432265/
12. Kanowski, S., Kinzler, E., Lehmann, E., Schweizer, A., & Kuntz, G. (1995). Confirmed clinical efficacy of actovegin in elderly patients with organic brain syndrome. Pharmacopsychiatry, 28(4), 125-133. https://doi.org/10.1055/s-2007-979604 https://pubmed.ncbi.nlm.nih.gov/7491366/
13. Mikhaĭlova, N. M., Selezneva, N. D., Kalyn, I.aB., Roshchina, I. F., & Gavrilova, S. I. (2013). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 113(7 Pt 2), 69-76. https://pubmed.ncbi.nlm.nih.gov/23994934/
14. Kopp H. (1979). Orale actovegin-Therapie bei zerebrovaskulärer Insuffizienz. Untersuchung über die therapeutische Wirksamkeit von actovegin forte Dragées bei Alterspatienten mit fortgeschrittenen zerebrovaskulären Insuffizienzerscheinungen [Oral actovegin therapy in cerebrovascular insufficiency. Studies on the therapeutic value of actovegin forte dragees in elderly patients with advanced cerebrovascular insufficiency]. Fortschritte der Medizin, 97(7), 307-312. https://pubmed.ncbi.nlm.nih.gov/437665/
15. Elmlinger, M. W., Kriebel, M., & Ziegler, D. (2011). Neuroprotective and anti-oxidative effects of the hemodialysate actovegin on primary rat neurons in vitro. Neuromolecular medicine, 13(4), 266-274. https://doi.org/10.1007/s12017-011-8157-7 https://pubmed.ncbi.nlm.nih.gov/21983748/
16. Kurkin, D. V., Morkovin, E. I., Kalatanova, A. V., Bakulin, D. A., Verholyak, D. V., Kovalev, N. S., Dubrovina, M. A., Tyurenkov, I. N., & Petrov, V. I. (2021). Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga [Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 121(7), 84-89. https://doi.org/10.17116/jnevro202112107184 https://pubmed.ncbi.nlm.nih.gov/34460162/
17. Tanashyan, M. M., Shabalina, A. A., Lagoda, O. V., Raskurazhev, A. A., & Konovalov, R. N. (2018). Multimodal approach to treatment of neurological complications of chronic brain ischemia. Terapevticheskii arkhiv, 90(12), 61-67. https://doi.org/10.26442/00403660.2018.12.000010 https://pubmed.ncbi.nlm.nih.gov/30701835/
18. Saletu, B., Grünberger, J., Linzmayer, L., & Stöhr, H. (1984). Zur Funktionsverbesserung des alternden Gehirns: Placebokontrollierte Pharmako-EEG und psychometrische Studien mit einem stoffwechselaktiven Hämoderivat (actovegin) [Functional improvement of the aging brain: placebo controlled pharmaco-EEG and psychometric studies with a metabolically active haemoderivative (actovegin)]. Zeitschrift fur Gerontologie, 17(5), 271-279. https://pubmed.ncbi.nlm.nih.gov/6395527/
19. Saletu, B., Grünberger, J., Linzmayer, L., Anderer, P., & Semlitsch, H. V. (1990). EEG brain mapping and psychometry in age-associated memory impairment after acute and 2-week infusions with the hemoderivative actovegin: double-blind, placebo-controlled trials. Neuropsychobiology, 24(3), 135-148. https://doi.org/10.1159/000119476 https://pubmed.ncbi.nlm.nih.gov/2135068/
20. Anderer, P., Saletu, B., Semlitsch, H. V., & Pascual-Marqui, R. D. (1998). Electrical sources of P300 event-related brain potentials revealed by low resolution electromagnetic tomography. 2. Effects of nootropic therapy in age-associated memory impairment. Neuropsychobiology, 37(1), 28-35. https://doi.org/10.1159/000026473 https://pubmed.ncbi.nlm.nih.gov/9438269/
21. Talypov, A. E., Ioffe, I.uS., Miatchin, M. I.u, & Kuksova, N. S. (2008). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 108(8), 20-23. https://pubmed.ncbi.nlm.nih.gov/18833103/
22. Demchenko, E. I.u, Kulakova, N. V., Semiglazova, T. A., Golovacheva, A. B., Borodulina, E. V., & Udut, V. V. (2008). Eksperimental'naia i klinicheskaia farmakologiia, 71(6), 13-15. https://pubmed.ncbi.nlm.nih.gov/19140508/
23. Martynov, M. Y., Bogolepova, A. N., & Yasamanova, A. N. (2021). Endotelial'naya disfunktsiya pri COVID-19 i kognitivnye narusheniya [Endothelial dysfunction in COVID- 19 and cognitive impairment]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 121(6), 93-99. https://doi.org/10.17116/jnevro202112106193 https://pubmed.ncbi.nlm.nih.gov/34283537/
24. Semlitsch, H. V., Anderer, P., Saletu, B., & Hochmayer, I. (1990). Topographic mapping of cognitive event-related potentials in a double-blind, placebo-controlled study with the hemoderivative actovegin in age-associated memory impairment. Neuropsychobiology, 24(1), 49-56. https://doi.org/10.1159/000119042 https://pubmed.ncbi.nlm.nih.gov/2132641/
25. Derev'yannykh, E. A., Bel'skaya, G. N., Knoll, E. A., Krylova, L. G., & Popov, D. V. (2008). Experience in the use of actovegin in the treatment of patients with cognitive disorders in the acute period of stroke. Neuroscience and behavioural physiology, 38(8), 873-875. https://doi.org/10.1007/s11055-008-9051-0 https://pubmed.ncbi.nlm.nih.gov/18802768/
26. Schaffler, K., Wauschkuhn, C. H., & Häuser, B. (1991). Study to evaluate the encephalotropic potency of a haemodialysate. Controlled study using electro-retinography and visual evoked potentials under hypoxic conditions in human volunteers (preliminary communication). Arzneimittel-Forschung, 41(7), 699-704. https://pubmed.ncbi.nlm.nih.gov/1772457/
27. Meilin, S., Machicao, F., & Elmlinger, M. (2014). Treatment with actovegin improves spatial learning and memory in rats following transient forebrain ischaemia. Journal of cellular and molecular medicine, 18(8), 1623-1630. https://doi.org/10.1111/jcmm.12297 https://pubmed.ncbi.nlm.nih.gov/24797227/
28. Shul'ginova, A. A., Laskov, V. B., Konoplya, A. I., & Karaulov, A. V. (2016). Eksperimental'naia i klinicheskaia farmakologiia, 79(7), 3-7. https://pubmed.ncbi.nlm.nih.gov/29782737/
29. Mychka, V. B., Khazova, I. E., Gornostaev, V. V., & Sergienko, V. B. (2005). Terapevticheskii arkhiv, 77(10), 20-24. https://pubmed.ncbi.nlm.nih.gov/16320679/
30. Vesel'skiĭ, I. S.h, Sanik, A. V., & Nasonova, T. I. (1995). Diagnostika mikrotsirkuliatorno-reologicheskikh narusheniĭ i ikh korrektsiia u bol'nykh s nachal'nymi proiavleniiami nedostatochnosti krovosnabzheniia mozga [The diagnosis of microcirculatory-rheological disorders and their correction in patients with the initial manifestations of insufficiency of the cerebral blood supply]. Likars'ka sprava, (9-12), 87-89. https://pubmed.ncbi.nlm.nih.gov/8983804/
31. Macheret, I.eL., & Khanenko, N. V.. (2002). Medykamentozne likuvannia khvorykh na dystsyrkuliatornu entsefalopatiiu [Drug therapy of patients with dyscirculatory encephalopathy]. Likars'ka sprava, (3-4), 84-87. https://pubmed.ncbi.nlm.nih.gov/12145902/
32. Fomin, A. A., & Pershakov, D. R. (2015). Khirurgia, (8), 54-57. https://doi.org/10.17116/hirurgia2015854-57 https://pubmed.ncbi.nlm.nih.gov/26356060/
33. Orlova, A. I., Sukovatykh, B. S., Artiushkova, E. B., & Gordov, M. I. (2017). Vliianie aktovegina i solkoserila na mikrotsirkuliatsiiu pri kriticheskoĭ ishemii nizhnikh konechnosteĭ v éksperimente [Effect of actovegin and solcoseryl on microcirculation in experimental critical lower limb ischaemia]. Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery, 23(1), 29-35. https://pubmed.ncbi.nlm.nih.gov/28574034/
34. Shamalov, N. A., Stakhovskaia, L. V., Shetova, I. M., Efremova, N. M., & Anisimov, K. V. (2010). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 110(9 Pt 2), 13-17. https://pubmed.ncbi.nlm.nih.gov/21462435/
35. Yakupov, E. Z., & Nalbat, A. V. (2015). Pokazateli vegetativnogo gomeostaza kak prediktory individual'nogo riska razvitiya insul'ta i ikh dinamika na fone lecheniya aktoveginom [The measures of autonomic homeostasis as predictors of an individual risk of stroke and their dynamics during therapy with actovegin]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 115(10 Pt 2), 31-42. https://doi.org/10.17116/jnevro201511510231-42 https://pubmed.ncbi.nlm.nih.gov/26977914/
36. Li, W., Guo, A., Sun, M., Wang, J., & Wang, Q. (2021). Neuroprotective Effects of Deproteinized Calf Serum in Ischemic Stroke. Frontiers in neurology, 12, 636494. https://doi.org/10.3389/fneur.2021.636494 https://pubmed.ncbi.nlm.nih.gov/34557139/
37. Kukhtevich, I. I., Aleshina, N. I., & Levashova, O. A. (2014). Aktivnaia neĭroprotektivnaia terapiia ostrogo karotidnogo ishemicheskogo insul'ta sredneĭ stepeni tiazhesti [The active neuroprotective therapy of acute carotid ischemic stroke of moderate severity]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 114(12 Pt 2), 38-42. https://doi.org/10.17116/jnevro201411412238-42 https://pubmed.ncbi.nlm.nih.gov/25726801/
38. Safarova, T. P., Yakovleva, O. B., Sheshenin, V. S., & Gavrilova, S. I. (2018). Metody augmentatsii antidepressivnoĭ terapii v gerontopsikhiatricheskoĭ praktike (on the model of complex therapy s vkliucheniem aktovegina) [Methods of augmentation of antidepressant therapy (on the model of complex therapy with the inclusion of actovegin) in gerontopsychiatric hospital]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 118(6. Vyp. 2), 55-63. https://doi.org/10.17116/jnevro201811806255 https://pubmed.ncbi.nlm.nih.gov/30346435/
39. Konoplya, A. I., Laskov, V. B., & Shul'ginova, A. A. (2015). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 115(11), 28-32. https://doi.org/10.17116/jnevro201511511128-32 https://pubmed.ncbi.nlm.nih.gov/26978048/
40. Skoromets, A. A., & Koval'chuk, V. V. (2007). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 107(2), 21-24. https://pubmed.ncbi.nlm.nih.gov/18379517/
41. Kudriavtsev A. A. (2000). Ostrye narusheniia mozgovogo krovoobrashcheniia pri operatsiiakh na organakh briushnoĭ polosti [Acute cerebrovascular disorders during surgical operations on abdominal organs]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 100(7), 14-17. https://pubmed.ncbi.nlm.nih.gov/10957794/
42. Kurkin, D. V., Bakulin, D. A., Morkovin, E. I., Kalatanova, A. V., Makarenko, I. E., Dorotenko, A. R., Kovalev, N. S., Dubrovina, M. A., Verkholyak, D. V., Abrosimova, E. E., Smirnov, A. V., Shmidt, M. V., & Tyurenkov, I. N. (2021). Neuroprotective action of Cortexin, Cerebrolysin and actovegin in acute or chronic brain ischemia in rats. PloS one, 16(7), e0254493. https://doi.org/10.1371/journal.pone.0254493 https://pubmed.ncbi.nlm.nih.gov/34260655/
43. Astashkin, E. I., Glezer, M. G., Vinokurov, M. G., Egorova, N. D., Orekhova, N. S., Novikova, A. N., ... & Sobolev, K. E. (2013, January). actovegin reduces the ROS level in blood samples of heart failure patients and diminishes necrosis of SK-N-SH human neuroblastoma cells. In Dokl Biol Sci(Vol. 448, No. 1, pp. 57-60). https://www.researchgate.net/profile/Evgeny-Astashkin/publication/303521579_DANBio1301005AstashkinKOR-1/links/574673e108aea45ee856190a/DANBio1301005AstashkinKOR-1.pdf
44. Suchkov, I. A., Mzhavanadze, N. D., Bogachev, V. Y., Bokuchava, M., Kuznetsov, M. R., Lukyanov, Y. V., Kelimbetov, R., Pang, H., & Araslanov, S. A. (2022). Efficacy and safety of actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO). International angiology : a journal of the International Union of Angiology, 41(5), 405-412. https://doi.org/10.23736/S0392-9590.22.04895-7 https://pubmed.ncbi.nlm.nih.gov/36264097/
45. Dittmar, K., & Krause, D. (1977). Erfolge kranken-gymnastischen Intervalltrainings bei Claudicatio intermittens [Success of physiotherapeutic interval training combined with standardized hemoderivative in intermittent claudication (author's transl)]. MMW, Munchener medizinische Wochenschrift, 119(11), 369-372. https://pubmed.ncbi.nlm.nih.gov/403421/
46. Dittmar, K., & Krause, D. (1977). Erfolge kranken-gymnastischen Intervalltrainings bei Claudicatio intermittens [Success of physiotherapeutic interval training combined with standardized hemoderivative in intermittent claudication (author's transl)]. MMW, Munchener medizinische Wochenschrift, 119(11), 369-372. https://pubmed.ncbi.nlm.nih.gov/403421/
47. Pfister, A., & Koller, W. (1990). Therapie der frischen Muskelverletzung [Treatment of fresh muscle injury]. Sportverletzung Sportschaden : Organ der Gesellschaft fur Orthopadisch-Traumatologische Sportmedizin, 4(1), 41-44. https://doi.org/10.1055/s-2007-993596 https://pubmed.ncbi.nlm.nih.gov/2193424/
48. Reichl, F. X., Holdt, L. M., Teupser, D., Schütze, G., Metcalfe, A. J., Hickel, R., Högg, C., & Bloch, W. (2017). Comprehensive Analytics of actovegin® and Its Effect on Muscle Cells. International journal of sports medicine, 38(11), 809-818. https://doi.org/10.1055/s-0043-115738 https://pubmed.ncbi.nlm.nih.gov/28895623/
49. Søndergård, S. D., Dela, F., Helge, J. W., & Larsen, S. (2016). actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle. European journal of sport science, 16(7), 801-807. https://doi.org/10.1080/17461391.2015.1130750 https://pubmed.ncbi.nlm.nih.gov/26744809/
50. Belikan, P., Nauth, L., Färber, L. C., Abel, F., Langendorf, E., Drees, P., Rommens, P. M., Ritz, U., & Mattyasovszky, S. G. (2020). Intramuscular Injection of Combined Calf Blood Compound (CFC) and Homeopathic Drug Tr14 Accelerates Muscle Regeneration In Vivo. International journal of molecular sciences, 21(6), 2112. https://doi.org/10.3390/ijms21062112 https://pubmed.ncbi.nlm.nih.gov/32204424/
51. Pavlov O. O. (2009). Klinichna khirurhiia, (1), 32-34. https://pubmed.ncbi.nlm.nih.gov/19670751/
52. Pavlov O. O. (2008). Klinichna khirurhiia, (9), 57-59. https://pubmed.ncbi.nlm.nih.gov/19275037/
53. Lominadze, A. A., & Sharvashidze, N. K. (2006). Georgian medical news, (138), 65-68. https://pubmed.ncbi.nlm.nih.gov/17057302/
54. Fedorovich A. A. (2012). Non-invasive evaluation of vasomotor and metabolic functions of microvascular endothelium in human skin. Microvascular research, 84(1), 86-93. https://doi.org/10.1016/j.mvr.2012.03.011 https://pubmed.ncbi.nlm.nih.gov/22497731/
55. Opanasenko, H. B., Bratus', L. V., Havenauskas, B. L., Honchar, O. O., Man'kovs'ka, I. M., Nosar, V. I., & Frantsuzova, S. B. (2013). Fiziolohichnyi zhurnal (Kiev, Ukraine : 1994), 59(1), 17-24. https://pubmed.ncbi.nlm.nih.gov/23713346/
56. Trofimova, S. V., Atakhanova, L. E., & Akhmedova, E. P. (2008). Advances in gerontology = Uspekhi gerontologii, 21(4), 625-632. https://pubmed.ncbi.nlm.nih.gov/19432215/
57. Krasnov, M. M., Baiandin, D. L., Vorob'eva, O. K., & Klimchenko, I.uG. (1995). Taktika vybora sosudistogo kollektor i sposoba vvedeniia lekarstvennykh veshchestv v metodike vnutriarterial'noĭ infuzionnoĭ terapii organov zreniia [Tactics in choosing a vascular collector and drug administration method in intra-arterial infusion therapy of organs of vision]. Vestnik of ophthalmology, 111(1), 23-27. https://pubmed.ncbi.nlm.nih.gov/7771038/
58. Shkrebets G. V. (2011). Vestnik of ophthalmology, 127(5), 38-41. https://pubmed.ncbi.nlm.nih.gov/22165098/
59. Fedorovich A. A. (2013). Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery, 19(4), 27-38. https://pubmed.ncbi.nlm.nih.gov/24429557/
60. Beetz, A., Machicao, F., Ried, C., Ruzicka, T., & Michel, G. (1996). Radioprotective effects of a protein-free hemodialysate in human epidermis. Skin pharmacology : the official journal of the Skin Pharmacology Society, 9(3), 197-202. https://doi.org/10.1159/000211416 https://pubmed.ncbi.nlm.nih.gov/8737917/
61. Liu, B., Li, X., Ai, F., Wang, T., Chen, Y., & Zhang, H. (2015). The influence of radiotherapy on IL-2 and IL-6 secretions of mucous membrane epithelial cells of wistar small intestine. Cell biochemistry and biophysics, 71(1), 35-38. https://doi.org/10.1007/s12013-014-0158-3 https://pubmed.ncbi.nlm.nih.gov/25081000/
62. Wang, X. W., Lin, X. Y., Bi, Y. H., & Han, J. Q. (2009). Zhonghua zhong liu za zhi [Chinese journal of oncology]., 31(10), 742-745. https://pubmed.ncbi.nlm.nih.gov/20021825/
63. Gulevsky, A. K., Moiseyeva, N. N., & Gorina, O. L. (2011). Influence of low molecular (below 5 KD) fraction from cord blood and actovegin on phagocytic activity of frozen-thawed neutrophils. Cryo letters, 32(2), 131-140. https://pubmed.ncbi.nlm.nih.gov/21766142/
64. Shevantaeva, O. N., & Kosiuga, I.uI. (2006). Eksperimental'naia i klinicheskaia farmakologiia, 69(2), 40-43. https://pubmed.ncbi.nlm.nih.gov/16845939/
65. Vakhrushev, Y. M., & Lyapina, M. V. (2017). Korrektsiia narusheniĭ funktsional'nogo sostoianiia tonkoĭ kishki kak novoe napravlenie lecheniia bol'nykh s metabolicheskim sindromom [Correction of small bowel function as a new direction for treating patients with metabolic syndrome]. Terapevticheskii arkhiv, 89(8), 43-49. https://doi.org/10.17116/terarkh201789843-49 https://pubmed.ncbi.nlm.nih.gov/28914850/
66. Kuznetsov, M. R., Bogachev, V. I., Sapelkin, S. V., Papysheva, O. V., Neskhodimov, L. A., Khotinskiĭ, A. A., & Mazitova, M. I. (2020). Dopolnitel'nye vozmozhnosti v konservativnom lechenii patsientov s posttromboticheskoĭ bolezn'iu nizhnikh konechnosteĭ [Additional possibilities in conservative treatment of patients with post-thrombotic disease of lower limbs]. Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery, 26(1), 31-36. https://doi.org/10.33529/ANGIO2020115 https://pubmed.ncbi.nlm.nih.gov/32240133/
67. Kuznetsov, M. R., Karalkin, A. V., Fedin, A. I., Virganskii, A. O., Kunitsyn, N. V., Kholopova, E. A., & Yumin, S. M. (2015). Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery, 21(3), 27-35. https://pubmed.ncbi.nlm.nih.gov/26355920/
68. Schubert, J., & Krost, B. (2006). Prävention von Lippen-Kiefer-Gaumen-Spalten. 25 Jahre klinische Erfahrung in der Senkung des Wiederholungsrisikos [Prevention of cleft lip and palate. Reducing risk of recurrence-a 25-year clinical experience]. Mund-, Kiefer- und Gesichtschirurgie : MKG, 10(5), 301-305. https://doi.org/10.1007/s10006-006-0020-x https://pubmed.ncbi.nlm.nih.gov/16944083/
69. Kuznetsov, M. P., Fedin, A. I., Karalkin, A. V., Frolov, K. B., Kunitsin, N. V., Yumin, S. M., Kholopova, E. A., & Knyazev, A. V. (2016). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 116(2), 34-41. https://doi.org/10.17116/jnevro20161162134-41 https://pubmed.ncbi.nlm.nih.gov/27029445/
70. Dong, Z. Y., Yang, S. R., Zhang, J. N., & Yao, Y. Z. (2021). Shanghai kou qiang yi xue = Shanghai journal of dentistry, 30(1), 89-92. https://pubmed.ncbi.nlm.nih.gov/33907787/
71. Wu, S. X., Cui, T. T., Zhao, C., Pan, J. J., Xu, B. Y., Tian, Y., & Cui, N. J. (2010). A prospective, randomized, multi-center trial to investigate actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 97(1), 113-118. https://doi.org/10.1016/j.radonc.2010.08.003 https://pubmed.ncbi.nlm.nih.gov/20826029/
72. Uchkin, I. G., Zudin, A. M., Bagdasarian, A. G., & Fedorovich, A. A. (2014). Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery, 20(2), 27-36. https://pubmed.ncbi.nlm.nih.gov/24961324/