Published: 25. April 2021.

Authors:     Dr. Zita Csomai physician, naturopath
Gábor Varga

Participants of the research team:

Tímea Gyertyán-Ági      special teacher, specialist in motor therapy
Nikolett Horváth            special educator, rehabilitational speech therapist
Erika Szücsné Göblyös qualified special educator, speech therapist, specialist in motor therapy
Anita Varga                    nurse, assistant, district nurse

Preface

Heart Rate Variability (HRV) is an indicator of the balanced functioning of the brain.

When we take a breath and inhale, our heartbeat accelerates, when we exhale, it slows down. Heart Rate Variability (HRV) measures the dynamic change of this process. The more evenly our heart beats, the greater the problem may be with the complex function of regulating heartbeat in our central nervous system. But also too high HRV value may refer to health problems, arrhythmia. Researchers relate the general health status mainly to the HRV value measuring the functioning of the vagus nerve. Diseases like diabetes, cancer, arteriosclerosis, schizophrenia, autismus, Altzheimer’s and Parkinsos’s disease, etc. are often related to lower HRV values. Since it is mostly the healthy functioning of the prefrontal cortex that is in charge of the HRV values, the integrity of brain functions determine and influence the incidence of the different chronic diseases.[i] The particular values of HRV are in connection with the extent of inflammatory processes in the body, the lower these values are, the higher certain inflammatory markers may be.[ii] The so-called cholinergic anti-inflammatory pathway is in charge of the anti-inflammatory effect of the vagus nerve. The impairment of the vagus nerve system and the increased inflammation due to that also predicts the eventual early death.[iii]

Researchers correlate the impairment of the cholinergic anti-inflammatory pathway with the emergence of respiratory failure due to COVID-19 infection especially in cases with the comorbidity of e.g. Altzheimers’s disease or unhealthy lifestyle.[iv] Researchers even defined a limit in the value of RMSSD, the HRV transmitted by the vagus nerve, below that the chance of developing chronic diseases, such as cardiovascular problems is significantly increased.[v]

In this regard it is a cause for concern that children suffering from type 1 diabetes mellitus, where the total or partial lack of insulin  and of the other associated peptide, proinsulin C-peptide is typically observed, HRV is significantly reduced.[vi]

Researchers state that this may be primarily due to the glycemic control, but the glycemic control is the best in those patients with type  1 diabetes, whose residual C-peptide production is relatively high.[vii] [viii] [ix]

It is worth mentioning that adding supplementary C-peptide significantly raises the low HRV value in  patients with type 1 diabetes mellitus.[x]

Regarding the patients in concern raised HRV may certainly be the result of the effect of proinsulin C-peptide on the central nervous system, despite the fact that the transfer of C-peptide through the blood-brain barrier is 5 times lower than the transfer of insulin.[xi]

In animal experiments the effect of c-peptide regarding the activation of the vagus nerve, administered directly into the brain, avoiding the blood-brain barrier, was the same in much less quantities than in systemic dosages.[xii]

In the future the idea of therapeutic application of proinsulin C-peptide may arise in people with chronic diseases due to its effect on raising and optimizating HRV and eventually regenerating brain functions, especially because it can easily and effectively get into the central nervous system through intranasal administration, avoiding the blood-brain barrier.[xiii]

Introduction

More than 2 years ago cosmetics containing proinsulin C-peptide became available in trade flows for the first time in the world. For a number of people this made it possible to use it off label, as a nasal spray, similarly to intranasal insulin. The experiences gained during these two years are astonishing and surprising. In our case study primarily the effect of C-peptide on HRV is analyzed, which is an indicator of the parasympathetic system of the body.

HRV, RMSSD, LF/LH rate were measured by Elite HRV equipment.

HRV value

HRV value is the responsiveness of the heart, it means the emotional, hormonal and neurological balance of the whole person, as well as the reactivity in life situations. The higher heart rate variability, that is HRV, is a complex measure of health. It describes how the heart can constantly change the period between two heart beats while reacting to the changing loads of the internal and external environment. The adaptive ability of the heart is based on the optimal interplay of the sympathetic and parasympathetic nervous system.  Adequate heart rate variability can be achieved in the body if the two systems are in balance. If the sympathetic system starts predominating, HRV is going to decrease. This in turn will increase the risk of developing cardiovascular diseases.

The HRV and RMSSD values change with age. Both too high and too low HRV may refer to health problems. It can also be said about HRV, that it reflects  the health state of the brain as well.

When analyzing the results we used the chart of the Elite HRV equipment, the ideal range concerning age was defined according to those values.

Figure 1 – Mean HRV depending on age

Mean HRV depending on age

AgeSexRMSSDElite HRV
18-25Male86.568.7
Female68.765.1
25-35Male66.064.5
Female55.761.8
35-45Male50.460.3
Female45.658.7
45-55Male39.656.7
Female41.757.4
55-65Male32.153.3
Female32.553.5
65-75Male30.652.7
Female24.849.4
75+Male33.153.9
Female25.549.9


LF/HF rate

The LF range is primarily determined by the sympathetic system. The LF value reflects the sympathetic and parasympathetic values in a rate of 3:1 (three-quarters sympathetic, one-quarter parasympathetic). The raised sympathetic activity may be caused by lack of sleep, stress or sickness.

The HF range is affected by the parasympathetic activity.

The LF/HF rate refers to the vegetative balance. The optimal value is 1.5-2 (ms²). If the value is lower than this, there is a parasympathetic, if higher, than a sympathetic prevalence.

Description of the proinsulin C peptide spray

The participants of our study were using the Vargapeptide skin-spray off label, as an intranasal spray, on their own responsibility. The spray is produced and distributed by the Max-Immun Ltd.  

This was applied in the same way as the intranasal insulin was and is administered in the population of children with Phelan-McDermid syndrome.

A 20 ml bottle contains a solutiotion of 18 ml C-peptide.One puff off the spray contains 0,108 mg proinsulin C-peptide. In Varga Peptide 0,5 this amount is half of it, 0,05 g, in Varga Peptide 2 the amount is 0,216 mg.The spray contains 0,8 % NaCl. The other ingredients fulfill the requirements of pharmaceutical grade purity.  The purity of  proinsulin C-peptide is 98-99%.

Description of the investigation

Selection

The participants of the study were selected in May 2020.

The first assessment consisted of an initial measurement and a survey using a questionnaire

The schedule of the measurements:

  1. initial measurement
  2. after one week
  3. after one month
  4. after 3 months
  5. after 6 months


Statistical data

There were 85 participants in our investigation. Out of these persons 2 patients quitted after 3 months, 1 patient could not continue due to the COVID pandemic and 1 patient with chronic diseases died (chronic renal disease, hypertonia), therefore the measurement after 3 month was already impossible to be executed.

The age range of patients was 3-78 years, the average age was 46.85 years. 

The distribution of sexes was 30 males, 55 females.

Figure 2 – Distribution of sexes


Diseases

The participants of the investigation were not selected according to certain diseases, therefore a wide range of  diseases can be found, and also each patient has more than one diagnosis, such as: 

Duchenne-syndrome, infantile autismus, moderate intellectual disability, dysgraphia, attention deficit, behavioural distuebance, sensory integration disorder, autismus, myocklonic epilepsy, stroke, balance disorder, vertigo, anxiety, synovitis, scoliosis, hypertonia, ragweed allergy, hypothyreosis, obesity, join pain, type 2 diabetes mellitus, lung tumor, breast tumor, skin cancer, spinal hernia, cardiomyopathy, colitis ulcerosa, reflux, autoimmune thyroid disease, prostate tumor, speech rythm disturbance, depression, deep vein thrombosis, gynecological tumor, sleeping disorder, EBV, pollen- and peanut allergy, neurasthenia, facial neuralgia, COPD, vaso-constcriction,  osteoporosis, dementia, ovarian cyst, hearing loss (80%), metabolic disorder, SIBO (Small Intestinal Bacterial Overgrowth), menopause, food allergy, multiple sclerosis, metastatic breast tumor, Traumatic Brain Injury, renal failure in final stage, benign skin tumor, panic disorder, spastic tetraplegy, perinatal injury, tinnitus, coordination disorder, migraine, Asperger syndrome, low back pain, chronic fatique, stress, Angelmann syndrome, pacemaker, torticollis, sciatica, pelvic tumor, dementia, earache, nervous exhaustion, Hashimoto thyreoiditis, hyperthyreosis, irritability, abdominal pain, nephritis, gravidity, nausea, weakness, fatty liver, arthritis rheumatica, Parkinson’s disease, extreme high blood pressure, asthma, Leiden mutation, COVID, colonic tumor, mixed disorder of the connective tissue, psoriasis, mitochrondial disease, Lyme disease, Bell-paresis, ADHD, immune deficit, Conn syndrome, autoimmune hepatitis.

Frequency and dosage

The dosage of C-peptide was started from type 0,5, than 1 and 2, according to age, than the dosage was changed according to the symptoms and the results.

The duration of appliance was 3-6 months.

Patients will continue taking C-peptide after 6 months as well.

Aspects of data collection and analysis

Each time of measurement the patients answered the items of the questionnaire, and the subjective observations were recorded as well.

Results

There was a great obstacle in the implementation of the investigation: the COVID-19 pandemic, therefore some of the measurement times were changed, and it also happened, that a measurement was skipped due to an infection.

The chart conains the patients’ age, sex, diagnosis, measured values and the changes in symptoms according to the questionaires. The type and dosage of C-peptide is also indicated.

The chart containing the data and results of each patient can be found in the Appendix.

Changes in HRV and RMSSD

In our investigation the HRV and RMSSD values were the following during the administration of C-peptide:

HRV and RMSSD was in the normal range according to age in 40 patients. In 43 patients both HRV and RMSSD values were low. The HRV and RMSSD values have been changed parallel to the administration of C-peptide.

Our measurements have also indicated that the HRV and RMSSD values were significantly influenced by the consumption of coffee, chocolate or cigarettes before the test. Patients under chemotherapy treatment had similar values. COVID infection also negatively affected HRV.

Age
Sex
DiagnoseDosageHRVRMSSDLF/HFComments
67 FemaleIBS pain of unknown origin                 6 months0.5 1×1 1×2 2×4 2×6 2×667 41 stress 50 46 (coffee, cigarette mask 59 (coffee, cigarette)80.21 14.44 26.25 19.35 47.730.51 8.04 1.08 1.42 2.15takes several medicine smokes, stressful earlier suffered from herpes, during the investigation none occasional cough stopped d joint paine relieved depression due to COVID worsened, hard for her to cope with the lock down
59 Femalemalignant lung and breast tumor                     6 months1 2×1 2×2 2×252 45 36 (did not take for 4 days during chemotherapy) 52 48 (coffee)30.3 18.74 10.53 29.26 22.151.72 2.37 4.91 0.98 2.32takes several medicine, receives chemotherapy smokes after 6 months chemotherapy check-up arm itching remained, numb  toes, surgery after the 2. test she is in healing phase, feels well, joint pain ceased general health better, but feels week due to chemotherapy and radiation therapy
64 FemaleColitis ulcerosa reflux                 6 months1 2×2 3×2 2×247 53 53 49 stressful smoked 63  stressful21.52 30.69 30.73 23.46 58.516.15 1.21 3.17 1.13 1.17smokes (less, earlier 1 now half packet,) minor waist pain ceased colitis ulcerosa 1x recurrenced, had bloody stool for 1 day, (CU since 1977) earlier these episodes lasted for 2-3 weeks if the C-peptide dosage was raised, got mild headache learns easier (e.g. dance choreography) short-term memory improved a bit does not catch infections
60 Female  autoimmune thyroid disease               3 months0.5 1x 2×1 0.5 2×2 1 2×260 49 ate sweets 51 52 ate chocolate, stressful50.56 23.46 26.97 129.634.79 1.13 0.45 0.54smokes 15-16 cigarettes daily, her pulse rises, this did not change   Decreased the dosage of C-peptide because of severe anxiety   After initial improvement  a stressy  period amplified her symptoms   Very stressful, because her husband got into hospital
70 Femalefacial neuralgia, COPD, vaso-constcriction,  osteoporosis, dementia, depression   6 months0.5 1x 2×1 2×2 2×243 59 64 46 ate chocolate, 43 stressful, upset16.24 46.84 62.29 19.82 16.391.52 6.61 1.36 1.4 0.73takes several medicine smokes reflux got better after 3 months had fracture after 3 months, recovered feels more often cold does not really feel improvement depressed mood, upset

Changes in HRV

Among the patients having low HRV at the beginning, the values of 28 patients improved due to the administration of C-peptide, in 8 cases there was an initial improvement, but later a relapse was experienced. In the cases of 6 patients there was no significant change. The value of 1 patient was fluctuating.

Figure 3 – Changes of HRV and RMSSD values in patients with low values at the beginning

Our observations were in the changes of HRV, that in the initial phase a deterioration often occurred. A HRV változásában megfigyeltük, hogy a kezdeti időszakban előfordul egy rosszabbodás. The time period needed for the improvement to appear was investigated and also the duration of it.

In 16 cases the values started improving already in the first month and these increased values remained all through the time applying C-peptide.

In 5 cases the first improvement was noticed in the 3. months, while in 2 cases the first in the 6. months.

Figure 4 – The improvement of HRV over time
Age SexDiagnosisDosageHRVRMSSDLF/HFComments
3 MaleDuchenne0.5 1x 2x 2-3x61 68 72 72  53.02 81.16 110.01 106.40.73 1,2 7.2 0.57Face redness milder Immune system strengthened Healing faster when catching a cold Motor abilities improved a lot, sits up independently lot better adaptation abilities can walk up stairs not disturbed by the vacuum cleaner attention span longer says more and more words

Deterioration of HRV

In the cases of 10 patients the initial HRV was in the normal range, but when measured later, worse results were found.

Figure 5 – Deterioration of HRV

4 patients from these 10 got coronavirus infection.

3 patients received chemotherapy, one of them had improved values after 5 months. Another patient showed improvement in the 3. months, but before the measurement in the 6. month received chemotherapy again and the measured values got worse again. 1 patient received both chemotherapy and radiation treatment.

1 patient felt very stressful, had a coffee before the measurement, wore facial mask, had a really hard time emotionally due to the lock-down of the COVID pandemic.

The values of 1 patient were worse in the 3. and 6. month, he reported to be very stressful, exhausted, works a lot, takes several medicine.

The values of 1 patient got worse in the 5. month, smokes a lot, anxious.

Age SexDiagnosisDosageHRVRMSSDLF/HFComments
59 Femalestiatica, palvic tumor
3 months
1 2×256 4437.83 17.243.08 4.34takes several medicine, recovered from COVID within 5 days   chemotherapy, radiation treatment   vitality improved, high pulse Due to covid changed for immunotherapy after 3 months
64 Femalecolon tumor, chemotherapy
0-3-5 months
 53 46 4932.33 19.4 24.253 46 49chemotherapy, medicine fluctuating health feels a lot more forceful  

Changes in LF/HF

The LF/HF rate was very high in a lot of patients according to our measurements. The changes were not so clear as those of HRV. A lot of patients had really high LF/HF rate, which refers to a dominating sympathetic functioning.   

The changes of values were also diverse.

Figure 6 – Changes of LF/HF rate

Changes of the LF/HF rate

The values of 4 patients were in the normal range and remained there as well.

The high values of 17 patients decreased and remained in the normal range while applying C-peptide.

In the cases of 8 patients az initial raising was found, than their values turned to be normal.

The values of 9 patients decreased, than raised back to high values. 2 of them received chemotherapy, 1 was infected by coronavirus, 1 patient had miscarriag, and 1 patient has inflammation in her body.

The values of 16 patients were very high, did not decrease. 5 of them received chemotherapy, 1 person had COVID infection as well, 1 patient receives radiation treatment. 2 patients take a lot of medicine. 3 patients suffer from severe anxiety and depression.  1 is a smoker, 1 has high blood pressure, 1 patient has autoimmune disease and 1 facial nerve palsy, as well as 1 patient has tetraplegia.

In 7 patients first raised, then very low values were experienced. 4 of them takes several medicines, 1 got COVID infection, 1 patient was under renal dialysis treatment, and 1 patient developed severe anxiety due to applying C-peptide, therefore the dosage could not be raised.

Very low value, the LF/LH rate below 1 was experienced in 1 patient, low values were found in 2 patients.

The LF/LH rate increased from a very low value, but did not reach the normal range in 8 patients. Interestingly, these patients had frequent herpes infection was found in their medical history.

The values of 4 patients became normal, starting from a very low value, their original diseases were earache, Bell-paresis, torticollis and epilepsy.

5 patients showed absolutely fluctuating values, each of them takes a lot of medicine regularly.

Changes depending on the dosage

The experience of our investigation pointed out that the changes both in HRV and the LF/HF rate dependent significantly on the dosage of C-peptide. In the cases of those patients, where the dosage was slightly or not changed at all, the values did not change. Therefore it is recommended in each case to change dosage according to symptoms and the results of the measurements.

Age SexDiagnosisDosageHRVRMSSDLF/HFComments
58 FemaleHypertension           6 months0.5 2×251 49 56 50 6027.99 24.83 38.94 26.11 48.692.62 3.93 2.28 2.26 4.18blood pressure stabilized in the normal range mood and sleeping improved copes with stressy situations better feels more forceful strain using the power improved a lot
20 MaleInfantile autismus     6 months0.5 2×163 68 58 47 4960.55 82.9 43.54 22.49 24.511.65 1.29 1.97 1.11 2.07calmer, sleeping became more restful started attending a college, tolerates more social life  concentration ability improved  
40 FemaleLatent hyperthyreosis Lyme disease0.5 2×155 52 53 52 5235.44 29.34 30.94 29.31 29.560.94 2.15 1.12 1.61 2.07Tolerates the hormonal changes due to the thyroid disease much better, the intensity of these significantly decreased Got pregnant but had a miscarrige, the cause of this is proved to be anti-cardiolipin positivity, investigation is going on Calmer, sleeps much better, became more forceful
61 MaleBell – paresis     6 months0.5 2×149 50 49 53 5124.15 26.04 24.03 30.86 26.750.48 0.88 0.29 1.37 1.26Bell paresis improved significantly, only a slight deviation of the mouth is experienced.
42 MaleFatty liver Autoimmune hepatitis0.5 2×159 67 55 4845.4 – 76.86 36.26 22.541.34 – 5.22 2.65 3.27values of laboratory test and general health improved strain using the power increased more restful sleep gained no weight.

Changes of symptoms

Subjective complaints and symptoms of our patients were also investigated. The patients reported general improvement of their symptoms, several patients described significant improvement in several symptoms.

3 patients felt that C-peptid was not beneficial for them, but in the answers of our questionnaire we could see that they are calmer, more balanced, they do not or less frequently catch infections.

Severe anxiety appeared in a patient with autoimmune disease, smoker, while applying C-peptide, therefore the dosage could not be raised.

25 patients felt more energetic.

Sleeping improved in 17 patients.

14 patients became less exhaustible.

In the cases of 12 patients infections were less frequent.

12 participants became more patient.

Speech improved in 11 patients, both in the cases of childhood disorder, and also adult problems.

Joint pain decreased in 11 patients.

Attention span became longer in 9 patients.

In 7 cases headache, migraine decreased.

6 patients feel less often cold since they apply C-peptide.

Motor skills improved, irritability decreased, depression  relieved, allergy or asthma got better, skin symptoms and memory improved, each of these in 6 cases.

Improvement of symptoms

Figure 7 – Improvement of symptoms

Deterioration of symptoms

There were rare cases, where the patients reported about deterioration of certain symptoms.

Anxiety increased in 3 patients.

In the cases of 2 patients differences between the pupils appeared.

Increased sweating, oversensitivity to scents, bad dreams, headache and feeling cold more often occurred, each symptom in 1 case. 

Figure 8 – Deterioration of symptoms

Anxiety, difference between pupils, increased sweating, oversensitivity to scents, bad dreams, headache and feeling cold more often 

Summary

Based on our present research it can be stated that the usage of intranasal C-peptide in a longer period (3-6 months) is secure, no serious side-effect or complication occurred during the application.  .

Both the objective, measurable values, such as HRV, RMSSD and the LF/HF rate indicated improvement in most cases, and also the subjective complains and symptoms of the patients significantly improved, and due to this their quality of life got better.

The symptoms and the measured values altered according to the dosage of the applied proinsulin C-peptide, therefore the dosage always has to be adjusted to the individual patient.

The patients were cooperating, they want to continue taking C-peptide in the future.

The exact effect, the more precise follow-up of symptoms and narrowing the patient groups in further research studies could provide more accurate image about the impact of intranasal C-peptide.

Appendix: Spreadsheet of clients

Age SexDiagnoseDosageHRVRMSSDLF/HFComments
3 MaleDuchenne0.5 1x 2x 2-3x61 68 72 72  53.02 81.16 110.01 106.40.73 1,2 7.2 0.57Face redness milder Immune system strengthened Healing faster when catching a cold Motor abilities improved a lot, sits up independently Lot better adaptation abilities Can walk up stairs Not disturbed by the vacuum cleaner Attention span longer Says more and more words
27 Maletendonitis, scoliosis1 1×1 3×0.5 és 2×0,5 1 2×261 57 61 59 54 (coke very tired)51.12 41.37 52.39 45.48 34.52.32 2.09 1.88 0.86 1.36Takes medicine Vegetarian Inflammation flares up less frequently Symptoms improved, than deterioríted again Sweating increased Fatigue got a bit better Attention more focused Forgot to blow C-peptide several times
31 Maleinfantile autismus, moderate intellectual disability   6 months0.5  1×1 2×1 2×1 2×271 67 66 57 6499.33 75.84 74.5 40.77 65.960.91 2.1 0.77 4.23 1.42Sleeping more restful, wakes up at night less often Slightly more skillful in daily activities Hasn’t started to speak yet
31 Maleinfantile autismus, moderate intellectual disability   6 months0.567 69 73 68 7078.65 87.33 117.39 81.38 93.221.13 2.16 3.24 1.29 1.82Slightly more skillful Better comprehension and execution of more complex requests        
45 MaleHypertension           6 months0.5 1×11 2×2 1 2×158 57 55 68 4842.75 41.1 35.18 81.12 22.845.75 1.67 1.58 2.9 5.89Takes medicine Knee pain slightly reduced Depression, irritability improved a lot,more balanced and patient at work as well. Concentration improved, more energetic. If he forgets to blow C-peptide, immediately more tired.  
67 FemaleIBS pain of unknown origin           6 months0.5 1×1 1×2 2×4 2×6 2×667 41 50 46 5980.21 14.44 26.25 19.35 47.730.51 8.04 1.08 1.42 2.15Takes several medicine Smokes, stressful Earlier suffered from herpes, during the investigation none Occasional cough stopped Joint pain relieved Depression due to COVID worsened, hard for her to cope with the lock down Takes coffee and smokes before the measurements
45 Maleragweed allergy       6 months1 1×1 1×1 3×1 4-5×1 8×154 55 46 58 5633.41 35.07 19.31 42.91 37.275.36 5.4 8,12 1.99 2.24No symptom, ragweed allergy milder after 3 months, after 6 months no symptom Joint pain ceased  
44 Femalehypo-thyreosis obesity joint pain, hyper-tension           6 months1 1×1 2×258 52 49 51 5644.28 30.2 23.46 28.12 38.340.41 4.01 1.13 4.5 1.59  Takes medicine Got COVID infection, than felt unwell due to high blood pressure, rosszul lett Insulin resistance is under examination Memory disturbance appeared After COVID her memory deteriorated, has difficulties to concentrate Feels less fatigue when applying C-peptide Due to COVID the measurement took place was 1 month later  
56 MaleDiabetes type 2, joint pain   6 months0.5 1×1 2×1 2×266 74 58 48 4971.37 120.47 43.97 22.25 23.920.96 2.19 0.56 1.57 0.65Takes medicine Did not feel significant change Feels a bit calmer and more balanced Works a lot, exhausted  
59 Femalemalignant lung and breast tumor                     6 months1 2×1 2×2 2×252 45 36 (did not take for 4 days during chemotherapy) 52 4830.3 18.74 10.53 29.26 22.151.72 2.37 4.91 0.98 2.32takes several medicine, receives chemotherapy smokes After 6 months chemotherapy check-up arm itching remained, numb  toes, surgery after the 2. test she is in healing phase, feels well, joint pain ceased general health better, but feels weak due to chemotherapy and radiation therapy
78 FemaleSkin- and breast cancer, spinal hernia CMP   3 months0.5 1x54 47 53 6133.05 21.05 30.53 51.051.04 2.25 3.41 0.58Takes medicine Did not perceive changes (negative thinking is typical, „glad to be alive”)    
13 MaleDysgrafia Attention deficit Behavioural disturbance       6 months0.5 1x       after 6 months 157 60 60 57 5740.07 49.37 48.12 41.71 40.211.68 3.02 2.58 4.8 2.94earlier severe depression, fear, fear of death Already after 3 months symptoms of depression rare, fear ceased Emotional stress, symptoms of adolescence Attention span longer, after 3 months concentration improved, better at school Attention deficit milder after 3 months, fatigue appears less frequently, more restful sleep at night  
3 FemaleSensory integration disorder, attention deficit               3 months0.5   1x 0.25  2-3x 0.5 3x65 60 79 6566.7 50.31 172.53 67.850.94 0.62 0.28 0.81After 3 months toilet trained Does not wake up at night, earlier did several times Has bad dreams, but less frequently Feeling of fear has changed Earlier took metallic things into her mouth, this stopped Much less aggressive, almost none at home Attention better Speech developed a lot, more clear articulation, can say whole sentences Eye-contact more stable
75 Femalehyper-tension, hypo-thyreosis     6 months1 1×1 4×1 8×1 0.5 8×160 76 69 60 6648.3 139.06 87.41 48.35 74.50.48 1.92 1.2 0.59 2.33Feels well, occasional pain unchanged, Wart on her neck smaller, Sleeping better already after the 3. month Tired Earlier had headache, ceased
64 FemaleColitis ulcerosa reflux                 6 months1 2×2 3×2 2×247 53 53 49 stressful smoked 63  stressful21.52 30.69 30.73 23.46 58.516.15 1.21 3.17 1.13 1.17Smokes (less, earlier 1 now half packet,) minor waist pain ceased colitis ulcerosa 1x recurrenced, had bloody stool for 1 day, (CU since 1977) earlier these episodes lasted for 2-3 weeks if the C-peptide dosage was raised, got mild headache learns easier (e.g. dance choreography) short-term memory improved a bit does not catch infections
60 Female  autoimmune thyroid disease               3 months0.5 1x 2×1 0.5 2×2 1 2×260 49 ate sweets 51 52 ate chocolate, stressful50.56 23.46 26.97 129.634.79 1.13 0.45 0.54Smokes 15-16 cigarettes daily, her pulse rises, this did not change   Decreased the dosage of C-peptide because of severe anxiety   After initial improvement  a stressy  period amplified her symptoms   Very stressful, because her husband got into hospital
56 Maleprostate cancer         6 months1 1×1 2×1 0.5 2×2 2×4 2×446 53 43 Aspirin protect Alfetim uno 48 5520.25 32.25 16.25 22.18 35.673.23 0.9 3.5 4.39 1.25Takes medicine Prostate cancer, bone metastasis (started earlier, decompression surgery) less fatigable (fatigable after chemotherapy) occasional headache, but disappears by itself feels well, last examination indicates slight progression
20 Malespeech disorder, depression       3 months0.5 1×142 27 51 4014.97 5.87 27.09 13.173.51 7.69 1.43 4.94takes medicine less depressed, feels well, can cope with difficult situations calm, improved a lot, feeling fear deteriorated body temperature changed from low to normal nightmares from 5 weekly to 1 weekly wake-ups at night did not change headaches less frequent pupils a bit bigger  
49 Femaledeep vein thrombosis, gynecological tumor, hyper-tension, sleeping disorder, EBV,         3 months0.5 1x37 51 62 61  11.43 27.71 56.01 53.232.18 1.33 0.22 1.54Takes medicine Immune system improved a lot, no eczema Coughs much less, at night not at all Moves more easily, does not lose balance Pain released, but still exists Mood a bit better, but has a lot of emotional stress Grinds her throat much less frequently, no dysphonic tone Much more forceful, memory improved, Jaw clicks milder, facial numbness got better Symptoms relieved (confinement) less sensitive to light and sounds    
41 Femalepollen- and peanut allergy varicose vein neurasthenia   6 months0.557 59 57 55 5941.08 46.56 40.19 35.37 46.182.65 2.27 3.32 1.9 2.09feeling heavy foot ceased memory improved got COVID infection before the 3.  months measurement
60 Nőtachycardia         6 months0.5 1×1 2×2 2×2 1 2×268 47 50 51 4283.54 20.68 25.05 26.91 15.390.26 1.13 0.97 0.99 2.54takes medicine earlier frequent herpes did not recurrence during the investigation ear peeling, itching ceased after 3 months more forceful, feels improvement in everything  
70 Femalefacial neuralgia, COPD, vaso-constcriction,  osteoporosis, dementia, depression   6 months0.5 1x 2×1 2×2 2×243 59 64 46 ate chocolate, 43,16.24 46.84 62.29 19.82 16.391.52 6.61 1.36 1.4 0.73takes several medicine smokes reflux got better after 3 months had fracture after 3 months, recovered feels more often cold does not really feel improvement depressed mood, upset
43 Femalehyper-tension left side ovarian cyst, hearing loss (80%),               6 months152 57 56 50 6929.93 41.97 38.94 26.13 91.952.68 0.48 6.74 3.24 0.56eczema ceased symptoms of pollen allergy did not appear had a mild heart attack due to emotional stress – catheterization pain in limbs ceased after 3 months very stressy due to work more forceful, but after the heart attack fatigable again regular headache released, ceased after 3 months attention skill better, memory improved but than deteriorated after the heart attack after 3 months felt definitely better, but after the heart attack it’s not the same  
53 Femalemetabolic disorder, small intestinal bacterial overgrowth (SIBO) menopause food allergy             6 months0.5 1x 2x 2x 2x66 48 60 72 5974.79 22.15 47.83 106.02 45.471.23 0.88 1.5 0.38 4.97earlier frequent herpes did not recurrence during the investigation frequent headaches became less frequent waist pain ceased after 3 months, but than recurrence due to constant sitting chole problem, vomits during migraine ceased more balanced, feels cold less frequently more forceful after 3 months, forceful after 6 months handwriting improved concentration ability better hard to cope with menopause, craving for sweets is worse  
52 FemaleSclerosis multiplex   3 months1 2×1 2×2 2×146 50 50 5619.7 25.43 25.68 39.084.57 3.62 1.78 1.66does not feel significant change does not catch infections constipation partly relieved before measurement coffee, cake, chocolate
33 FemaleIBS anxiety     6 months1 1x 2x 4x 2x60 65 66 73 7649.05 70.56 74.79 118.44 137.232,57 1.06 1.41 1.16 1.74after 3 months diarrhea ceased (no stool at the week-end) better in standing up for herself jobban ki tud állni magáért headache less frequent
46 Femalebreast cancer, bones and brain metastasis   6 months0.5 1-es56 61 63 58 5237.45 53.45 61.52 44.16 28.742.09 0.58 1.14 2.38 2.19medications, chemotherapy mood swings, became oversensitive to odor
70 Malebrain injury stroke hyper-tension         3 months0.5 2×269 51 74 6989.4 27.22 126.01 89.461.56 2.57 5.02 0.76takes several medicine skin improved after 3 months feels cold less frequently, limbs less cold sleeps more restfully concentration, memory did not improve speech improved, comprehension did not less clumsy
51 Femaleend-stage renal failure, hyper-tension malignant skin tumor, panic disorder   6 months0.5 1×1 2×170 67 86 – 5992.16 77.87 260.17 – 46.850.14 0.16 8.9 – 0.46takes a lot of medicine, she is under dialysis treatment ear clicking ceased, occasional headache had knee swelling and pain, pain stopped, swelling remained feels cold less frequently anxiety, panic did not improve, urine returned in 4-5 weeks, but her condition deteriorated after a cystitis 3 months check-up missed due to COVID
59 Malestroke                   6 monthsdosage unclear42 49 78 68 6515.15 24.37 161.4 101.74 68.631.00 2.49 2.3 3.51 1.02takes medicine had herpes zoster, ceased pain due to duodenal ulcer did not appear feels cold less frequently, sleeps better short term memory, reading improved Feels to have reacedh 90 % of his capacity before the stroke Felt 80-85% improvement after 1 month Forceful  
26 Maleathetosis cerebral paresis spastic tetraplegia perinatal injury         6 months1 1x77 68 80 77 79152.38 84.15 181.63 151.56 167.672.19 4.3 2.81 3.86 2.21cold feet symptom decreased sweating released after 3 months significant changes in muscle tone bending better when seated a few words more clear less food falls out when he is eating 6 months: athetotic movements decreased Lines are finer when painting severe sweating released understand longer textes better faster in typing on the computer  
46 Femaletinnitus coordination disorder migraine   3 months0.5 0.5 0.5 0.2552 69 66 7329.43 88.25 72.78 118.322.52 0.98 2.03 0.93earlier had herpes, it did not appear during the investigation sleeps better, more forceful attention a bit more concentrated tinnitus did not change after 1-2 months dosage decreased to 1,25 because of bad dreams and fears
34 MaleAsperger                             6 months0.5 1x 0.25 1x 1x 1x58 40 55 46 5244.39 13.89 35.73 20.54 30.153.58 4.45 4.2 4.47 1.94takes medicine sleeps more restfully, less fatigue energetic (6 months) concentration improved a lot bipolar depression improved than it’s changing headache released than fluctuating, not so sensitive to bright lights does a physician found one of his pupils smaller his opinion is that C-peptide is not useful therefore often misses usage feels stressy when applying therefore dosage is decreased anxiety increased
18 Femaleautismus pervasive developmental disorder myoclonic epilepsy0,5 5x 1-es 2×1 2×2 2×374 77 63 65 58122.84 148.86 61.06 67.53 43.840.85 1.18 1.33 0.52 1.59takes medicine for epilepsy sleeps better muscle twitching seemed to be improved after 3 months, but it became fluctuating again no myoclonic epilepsy a physician found one of his pupils smaller says surprising new things, that was not typical before after 6 months után sometimes communicates surprisingly well, speaks as an adult, draws consequences, rounds  
24 Femalestroke hypothyreosis1 2x66 59 62 5173.91 45.82 55.37 26.741.00 1.14 2.19 2.16takes medicine QUITTED – since her facial paralysis did not improve asthma improved feels continuous improvement insensitive facial half moves better
26 MaleAsperger food allergy, balance disorder, dizziness, EBV0.5 2x56 65 62 54 5437.96 66.91 56.28 33.46 34.082.97 0.76 8.21 3.67 4.76symptoms of eczema decreased reaction to sweets: spinning, wandering stereotypic behaviour milder balance disorder improved dizziness decreased 3 months: 6times/day, 10/5 grade after 6 months:1-2/week, 10/2 grade can sit still, study for 10-12 hours, earlier walked around pupil dilation ceased speech more clear social communication improved a lot more independent, goes shopping independently stress tolerance improved
53 Femaleanxiety, waist pain  1 1×165 4968.88 24.271.4 4.86cigarettes 1 packet /day 5 months check-up
58 Femalestress, constant fatigue1 1×155 6236.78 55.61.88 1.58  4 months
24 Femaleautoimmune0.5 1x 0.5 2x71 7398.41 117.970.51 0.75  4 months
27 MaleAngelmann syndrome1 1×175 71 67133.49 101.61 79.17– 0.34 0.56sleeps better, behaviour more balanced aggressive behaviour decreased willingness to communicate increased did not start speaking 3 months – 5 months
70 Male2 stroke pacemaker1 1-171 54 81103.22 33.89 190.390.7 1.48 1.04takes medicine speech improved 3-6 months
67 Femaletorticollis1 1-125 63 6629.77 61.27 73.920.69 1.34 0.14took pain killer, that she did not need any more vitality, exhilaration increased first fatigue released after 1 week,  than the pain after 3 months 3-5 months
50 Femaleautoimmune, reflux1×2  36 44 4010.59 17.61 13.786.66 1.38 1.88vitality, activity improving 3-5 months 5 months: hasn’t used for 2 weeks
59 Femalestiatica, palvic tumor       3 months1 2×256 4437.83 17.243.08 4.34takes several medicine, recovered from COVID within 5 days   chemotherapy, radiation treatment   vitality improved, high pulse Due to covid changed for immunotherapy after 3 months
66 Femalehyper-tension 4 months1 1×149 5324.2 31.062.53 2.064 months decreased dosage of medication
72 Maledementia tumor -radiation therapy, surgeries   3 months1 1×161 6852.93 85.833.22 3.11speech ability fluctuating, more cheerful, more energetic
60 Femalebilateral earache dizziness, nervous exhaustion   6 months1 1×161 66 7652.28 71.47 141.070.22 1.11 1.65dizziness ceased earache persisted   4-6 months
56 Femaleautoimmune Hashimoto 2 atrophic thyroid lobe   6 months0.5 1x 1 2×239 49 5512.64 12.83 36.563.02 1.43 1.141 week 6 months no other data
54 Femalehyperthyreosis   irritable, low stress tolerance, fatigue for 5 years, spinal hernia frequent migraine   3 months1 2x92 9022.53 22.01 (erős stressz)2.86 2.14takes medicine forceful, cheerful, energetic sleeps well migraine ceased   3 months
24 Femaleabdominal pain of unknown origin, vaginitis nephritis, frequent migraine reflux   3 months1 2x59 6046.98 50.122.01 1.09 (nagyon beteg felfázás)headache ceased other problems persisted caught a cold several times, inflammation fluctuated   received antibiotics 3 months
44 Femaleautoimmune disease   2-4 months0.5 2×2 2×2-347 47 5420.79 21.56 33.101.29 6.53 2.64energetic cheerful sleeps well
28 Femalepregnant nausea weakness0.5 1-155 5735.34 3.72 (?)1.75 1.86initial measurement at 4. months of pregnancy, after 1 month of C-peptide application in the 9. month: worried because the amniotic fluid is too little  
27 Malesclerosis tuberosa   1 months1 1×152 45 6029.17 18.43 49.90.88 1.46 1.00more communicative can manage timing of sleeping periods 1 week 1 month
44 Femalefatty liver high liver enzyme   3 hónap0.5 2×1 2×2 1 2×169 72 68 62 6091.49 110.87 82 56.34 50.585.83 1.81 3.97 2.91 1.41a bit more forceful does not feel a big change 0-1week – 1 month – 3 months
58 FemaleArthritis rheumatica, thyreoid   6 months1 2×242 54 5515.05 34.42 35.551.56 0.9 1.47Takes medicine, forceful, sleeps well, has great vitality 0.- 3 months- 6 months  
66 Femaletumor lymph node swelling at the collarbone1 1-151 44 47 4926.84 17.43 21.69 23.961.03 1.6 0.75 2.03swelling shrunk 0.-1-3-5 month used 1.5 month before the initial measurement, thank stopped using it.
76 FemaleParkinson’s disease   6 months 36 51 52 5810.46 28.04 29.24 44.221.95 0.88 0.7 0.89Takes medicine Feels much better More forceful  
77 Femaleextreme hyper-tension arrhythmia   6 months0.5 1 x76 79 78143.25 169.37 161.090.43 0.78 0.93Takes a lot of medicine Feels very well, full of energy Could decrease the dosage of some medication  
24 Malenone   0-3-5 months0.5 2×263 73 5960.95 114.3 46.021.47 0..56 3.64did not apply 2 weeks before the last measurement did not feel any special
11 Malenone   0-3-5 months1 2×164 71 6564.47 100.49 69.240.8 1.59 2.05 
43 Maleanxiety, skin problems   6 months1 2x 2-3x62 58 6255.81 43.48 57.936.35 6.39 3.68feels much better, not so anxious  
29 Maleskin allergy, asthma, migraine  0.5 3-3 2-249 72 6523.94 110.61 70.472.04 4.49 4.05asthmatic and allergic symptoms revealed significantly
62 FemaleLeiden mutation right side deep vein thrombosis   0-3-5 months 55 60 7335.24 49.35 111.520.48 1.38 0.54takes a lot of medicine
77 Femalehypertension   6 months0.5 1-158 61 56 6344.29 51.78 36.91 60.560.82 1.17 0.37 0.41doesn’t want to raise the dosage of C-peptide, because does not dare to decrease the dosage of her prescribed medicine
77 Female3 stroke hyper- tension perforated heart cardiomyopathy leg pain   5 months1 1-148 64 7622.37 64.98 143.370.98 0.92 5.67  takes a lot of medicine forceful, cheerful leg pain ceased due to local treatment  
9 MaleCOVID last measurement performed right after  COVID   6 months0.5 1-178 72 75 75160.17 107.41 134.82 134.751.57 1.09 0.45 1.28forceful, sleeps always superficially   no change   38 degrees at night  
55 Malecolon tumor, has already applied C-peptide   3 months1 2-263 4958.86 24.65  3.23 2.85after colon surgery due to tumor, chemotherapy
56 Femalefatty liver, mild hyper-tension   6 months1 R3 E2 R4 E240 44 5113.11 17.94 27.012.68 1.54 1.74 
47 Femalejuvenile Parkinson’s disease   1-4-6 months0.5 1 2   0.5 2×228 41 49 43 416.05 14.48 23.87 16.68 14.23.13 4.14 0.82 2.25 8.11Takes Madopar in every 3 hour, highly fluctuating difficult for her to adjust it to the medication had to decrease dosage to 0.25 did not apply it for 2 weeks before the 4 months measurement
52 Femalepollen-allergy suffered from COVID   6 months1     4×2– 65 66 78– 67.83 75.18 157.95– 1.01 1.8 2.57 
23 FemaleLeiden mutation   3 months0.5 1-150 7726.64 147.850.6 1.23Better mood, forceful In case of leaving it out for 1-2 days, a lot more exhaustible, bad mood  
64 Femalecolon tumor, chemotherapy   0-3-5 months 53 46 4932.33 19.4 24.253 46 49chemotherapy, medicine fluctuating health condition feels herself a lot more forceful  
53 FemaleDiabetes type 2, Mixed Connective Tissue Disease  (MTSD)   0-3-6 months1 2x32 52 52 478.22 29.38 69.44 21.091.92 1.29 0.28 0.59Takes a lot of medicine Foot swelling, skin problem and fatigue ceased than reoccured because of stress, emotional problems
75 MaleChronic renal failure Hyper-tension Occlusion Arterial stenosis, Tinitis, Lumbal intervert. disc. disorder  1 1×1 0.5 2×261 7953.13 167.530.83 1.1physical capacity improved sleeping got a bit better     hyper the patient died, therefore the 3 months measurements can not be reported  
58 FemaleHypertension           6 months0.5 2×251 49 56 50 6027.99 24.83 38.94 26.11 48.692.62 3.93 2.28 2.26 4.18blood pressure stabilized in the normal range mood and sleeping improved copes with stressy situations better feels more forceful strain using the power improved a lot
20 MaleInfantile autismus     6 months0.5 2×163 68 58 47 4960.55 82.9 43.54 22.49 24.511.65 1.29 1.97 1.11 2.07calmer, sleeping became more restful started attending a college, tolerates more social life  concentration ability improved  
40 FemaleLatent hyperthyreosis Lyme disease0.5 2×155 52 53 52 5235.44 29.34 30.94 29.31 29.560.94 2.15 1.12 1.61 2.07Tolerates the hormonal changes due to the thyroid disease much better, the intensity of these significantly decreased Got pregnant but had a miscarrige, the cause of this is proved to be anti-cardiolipin positivity, investigation is going on Calmer, sleeps much better, became more forceful
58 FemalePsoriasis Rhinitis allergica     6 months0.5 2×1  40 43 55 53 4913.09 16.7 36.61 30.86 24.384.77 7.81 0.98 1.37 5.78  Number and thickness of psoriasis plaques,hyperaemia significantly decreased, in certain places ceased. Runny and clogged nose, eyes tearing ceased after 1 week of application, stopped taking antihistamine pills  
66 MaleStroke hyper-tension1 2×2   Had only one measurement due to COVID infection
52 FemaleMitochondrial disease, facial numbness149 52 57 61 5424.01 29.99 41.39 53.21 33.271.36 1.77 1.1 1.43 0.71Visual field results better at eye examination Facial numbness decreased Physical capacity, energy got better  
24 FemaleLyme-disease, conversion disorder   0-1-3 months0.5 2×147 58 52 5721.28 44.26 29.35 39.981.7 1.57 3.57 1.93  According to her narrative she did not feel improvement while applying C-peptide, QUITTED the programme  
61 MaleBell – paresis     6 months0.5 2×149 50 49 53 5124.15 26.04 24.03 30.86 26.750.48 0.88 0.29 1.37 1.26Bell paresis  improved significantly, only a slight deviation of the mouth is experienced .
42 MaleFatty liver Autoimmune hepatitis0.5 2×159 67 55 4845.4 – 76.86 36.26 22.541.34 – 5.22 2.65 3.27values of laboratory test and general health improved strain using the power increased more restful sleep gained no weight.
5 FemaleADHD immune deficiency         6 months0.5 1×167 65 57 58 6579.28 68.3 41.87 42.12 66.630.63 1.26 1.23 1.5 1.26Immune status significantly improved, infections less frequent, duration shorter. The characteristic features of ADHD –almost completely resolved. Positive changes proved by an Assessment Committee Integrated into a class Attention more focused, understands tasks, executes assignments.
73 MaleConn syndrome                                   6 months 59 50 54 4946.34 25.7 33.81 24.34 22.860.58 1.87 1.86 0.54 0.24Earlier constant arrhythmia became less frequent. RR values are balanced, very rarely low blood-pressure. Stamina improved a lot, can afford much more.When Herpes labialis appeared, C-peptide applied on the skin, blisters ceased in 1 day. Got COVID infection during the investigation, hospitalized for 11 days, unconscious for 3 days. During transportation right arm was bruised, haematoma appeared. Recovered in 1 day, after blowing C-peptide on the skin. Applying VargaPeptide 2, health condition improved, after returning home her weakness and fatigue gradually decreased, works in the garden, takes care of himself, walks a lot, a few km-s.  

List of figures

Figure 1 – Mean HRV depending on age.
Figure 2 – Distribution of sexes.
Figure 3 – Changes of HRV and RMSSD values in patients with low values at the beginning
Figure 4 – The improvement of HRV over time.
Figure 5 – Deterioration of HRV.
Figure 6 – Changes of LF/HF rate.
Figure 7 – Improvement of symptoms.
Figure 8 – Deterioration of symptoms.

References


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