Effectiveness of Systemic Medicine in the treatment of Diabetic Peripheral Neuropathy.

Effectiveness of Systemic Medicine in the treatment of Diabetic Peripheral Neuropathy.
Olalde J.A. (a), Magarici M. (b), Amendola F. (c), del Castillo O. (d), De Arriba, C (e).
(a) Founder of Systemic Medicine. President of Adaptógenos Educational Medical Centers.
(b) Medical Director of Adaptógenos Educational Medical Centers (CMA), Caracas, Venezuela.
(c) Assistant Doctor, Medical Direction of Adaptógenos Educational Medical Centers.
(d) Engineer, Methodology and Statistics, Assistant, Adaptógenos Educational Medical Centers.
(e) Assistant Chemist, Medical Direction, Adaptógenos Educational Medical Centers.

Summary

The effects of a combination of medicinal plants, formulated under the principles of Systemic Medicine, were evaluated in 135 patients with Diabetic Peripheral Neuropathy. This was carried out by means of a retrospective, multicentric and descriptive study that lasted two years. This treatment improved the signs and symptoms associated with neuropathy in 71% of patients, without causing side effects. An increase in the improvement of the quality of life was evidenced in 90.4% of the patients, as well as an excellent tolerance to the treatment in all cases. Synthetic medicines conventionally utilized such as anti-inflammatory medicines, antidepressants, anticonvulsants, may produce side effects such as sleepiness, ataxia and/or hepatotoxicity, among others. That is why the herbal combination, under the point of view of Systemic Medicine, thanks to its therapeutical benefits, improvement in the quality of life and absence of side effects in patients, must be considered as a first choice treatment in this entity.

I. Introduction.

Diabetes mellitus is a chronic disease that affects a considerable percentage of the Venezuelan population. It is a high priority problem worldwide.
As life expectancy has increased, due mainly to the fact that there is a better control of infectious diseases, there has been a significant increment in degenerative diseases. This increase has been observed consistently during the last decades; from being the 22nd cause of death in Venezuela in 1955, it has become the 7th cause of death in the last years. (1).
Approximately 10% of diabetic patients suffer from type I Diabetes. In these patients, the pancreas does not produce or barely produces insulin, that is why they need insulin every day to be able to metabolize the food they eat. The other 90% of diabetic patients suffer from type II Diabetes, including those with decrease of insulin secretion and those who suffer from resistance to insulin. Its treatment, in general terms, consists in a special diet, exercise, occasional insulin and oral hypoglycemiants, which stimulate the pancreas to increase insulin secretion or make body tissues sensitive to the quantity of insulin produced. These synthetic medicines can result in adverse side effects, such as: diarrhea, meteorism, hypoglycemia, skin rashes, anemia and liver damage. After a variable period of time, these medicines can lose their effectiveness.
A shortened life, physical suffering, high medical costs, high social cost, job absenteeism, disability and vital limitations are common consequences of this heterogeneous syndrome.
With time, high glycemia levels lead to damage in blood vessels and nerves, resulting in neuropathy, retinopathy, cardiopathy and many more diabetic complications.
Diabetic patients may develop peripheral neuropathy at any time, but a significant clinical neuropathy can be developed in the first ten years following the diagnosis. The risk of developing this complication increases with time. It is estimated that approximately 60% of people with diabetes have a type of neuropathy. (2).
Diabetic neuropathy can be peripheral when it affects the nerves of the extremities; the symptoms include numbness, insensitivity to pain or change of temperature, tingling, burning or stabs of pain, sharp pains or cramps, extreme sensitivity to the touch, loss of balance or coordination.
Neuropathy can be autonomic when it affects the nerves that supply the internal organs, the processes and the systems of the heart, the digestive system, the sexual organs, the urinary tract and the sweat glands. The symptoms include: incontinence, digestive problems, low blood pressure, dizziness, incapacity to feel pain, hypoglycemia, hyperhidrosis, etc.
Due to the multifactorial etiopathogenesis of diabetic neuropathy, there is no ideal treatment for any of the typical syndromes. In general, the therapeutical attempts are oriented to the peripheral polyneuropathy.
The conventional treatment includes medicines like AINES (but due to their potential renal toxicity and the fact that in theory they can alter the nervous transmission as they inhibit the synthesis of prostaglandins, these medicines should be used with caution (47)), tricyclic antidepressants such as amitriptyline (which use in patients with neuropathy is complicated, since several of its side effects tend to be more severe in these patients: postural hypotension, urinary retention, intestinal hypomotility and dry mouth (48)), and carbamazepine (which most frequent side effects are dizziness, nausea, erythema and in some cases leucopenia (48)).
In the Adaptógenos Medical Centers in Venezuela, many patients with this pathology have received conventional treatment complemented with medicinal plants, where it was evidenced a substantial clinical improvement that significantly reduced the suffering and the medical costs of these patients.
According to Systemic Medicine (3,4), the potential of survival of any living system depends on the correction of three elements that coexist in a triangular relationship. These factors are: Energy, Intelligence and Organization. Energy is defined as the physiological mechanisms associated to the synthesis of ATP (such as the oxidative phosphorylation, tricarboxylic acid cycle, beta-oxidation, etc.). Biological intelligence is the element responsible for the regulation of the neuroendocrine, biochemical, immunological and cellular processes. Lastly, Organization refers to the structure and function of the organs. Under these concepts, survival (or health) of a human being can be improved by increasing any of the three components of that triangle, due to their interdependence. The systemic treatment includes the combination of superior plants that modulate the three axes of the triangle of survival or health, maximizing the benefits in health and contributing to improve the clinical evolution of the patient, as well as his/her quality of life.
The complications associated with Diabetes, Diabetic Peripheral Neuropathy in particular, have driven us to search for therapeutical alternatives. Thus, as we will see in the next section, the philosophy of Systemic Medicine offered the principles to design a successful protocol of medicinal plants. These are the reasons why we have carried out a retrospective, multicentric, descriptive study to confirm the effectiveness of superior plants (1) utilized under the principles of Systemic Medicine, in patients diagnosed with Diabetic Peripheral Neuropathy, who were treated by doctors in the Adaptógenos Medical Centers (CMA) and Adaptógenos Medical Units (UMA) (2).

II. Theoretical Framework

The handling of a diabetic patient and his/her complications is complex, and the use of synthetic medicines is not successful in a large number of cases. Hence the importance of finding alternative treatments.
In the last years there has been a constant increase in the use of Complementary Therapies all over the world. This is the result of increasingly frequent clinical evidences that endorse the use of some of these therapies as support to conventional treatments, making them more accepted and recommended by doctors.
The excellent tolerability of medicinal plants, their proven benefits and the absence of side effects, make them extraordinary complements for the treatment of patients with diabetic foot, since they improve the Quality of Life and extend the Potential of Survival of these patients.
The medicinal properties of some of these plants have been known for more than 3,000 years, but it was only in the last few years when technology was able to isolate their active principles. Once they were known, these substances were evaluated using animals before they were used in human beings. The use of different medicinal plants with different active principles, but with an additive or synergic action, allows to achieve an improved effectiveness and response.

III. Explanation of the Systemic Protocol summarized and applied to the treatment of Diabetic peripheral neuropathy

The formulation of this protocol (5) is based on the systemic triangle of health and on the triangle of Biological Intelligence. (Fig. 1). This combination of superior plants modulates the three axes of the survival (health) triangle, contributing to improve the clinical evolution of patients, as well as their quality of life.

Fig. 1

Figure 1: Systemic Protocol summarized for diabetic peripheral neuropathy.

Stimulation of Energy, Organization and Intelligence in the triangle of Health.

a) Stimulation of the Energy Axis.

Panax ginseng: its active principles bind to the beta-adrenoreceptors of the cellular membrane, releasing the system of messages of the second transmitter (AMPc). The signal travels to the mitochondria, to increase the activity of malate dehydrogenase, citrate synthetase and succinate dehydrogenase, enzymes of the tricarboxylic acid cycle. This makes the production of ATP go up, increasing the levels of energy, utilizing glucose as fuel (6). Fig. 2.

Figure 2: Energizing Mechanism of Ginsenosides.

As energy is increased, a larger triangle of health is obtained, because the biological Intelligence of the system has more capacity to organize. However, Panax ginseng is a phytomedicine capable of simultaneously increasing Energy, Intelligence and Organization, in each cell of the living system, as shown further on.

b) Stimulation of the Organization Axis.

Vaccinum myrtillus: the antocyanosides of this plant reduce the deposits of arterial plaque, stimulate the release of vasodilator substances such as prostacyclin (PGI2), which protect the endothelium, inhibit platelet aggregation and prevent the synthesis of pro-inflammatory compounds. These mechanisms increase the blood flow and the supply of nutrients and oxygen, which are vital in the treatment of microangiopathy and of diabetic peripheral neuropathy. (7,8).

c) Stimulation of the Intelligence (Cellular) Axis.

Panax ginseng: its ginsenosides improve cellular Intelligence by stimulating the beta pancreatic cells, and this stimulates the production of insulin and the number of insulin receptors (9). Ginsenosides contribute to the reduction of glucose levels, which is helpful to diabetic patients (6).
The mitochondrial metabolism generates ATP and increases the intracellular relation of ATP/ADP, which results in the closure of ATP-sensitive channels of potassium of the cellular membrane. The closure of these channels depolarizes the membrane and produces the opening of voltage-sensitive channels of calcium, which leads to the quick entry of calcium in the cell. The increase of intracellular calcium stimulates the translocation of granules that contain insulin to the plasmatic membrane and the release of insulin by exocytosis (10). (Fig. 3

Figure 3: Insulinogenic Mechanism of Ginsenosides.

Diabetic neuropathy corresponds to a complication of hyperglycemia, related to the glycosylation of myelin and to the activation of Aldose Reductase (an enzyme that is present in peripheral nerves, and which catalyzes the reduction of glucose to sorbitol). Hyperglycemia activates the Aldose Reductase of the peripheral nerves, producing an increase in sorbitol and a blocking of the Na+/K bomb of the cellular membrane, and this leads to the entry of Na+, water, axonal edema and a drop in the speed of nervous transmission, which are characteristics of diabetic neuropathy.
Ginsenosides block the channels of Na+ of the cellular membrane, which prevents the entry of Na+ and water, decreasing the axonal edema and increasing the speed of nervous transmission. In addition, they offer an activity that inhibits protein glycosylation, which benefits neuropathy and other diabetic complications (11-13).

d) Stimulation of the Intelligence (Biochemical) Axis.

Rhodiola rosea: its main active principles are: phenylpropanoids and flavonoids. These substances explain its adaptogenic, cardiopulmonary protective properties and activity on the Central Nervous System, mainly attributed to its capacity to modulate the levels and activities of biogenic amines such as: serotonin, dopamine and norepinephrine in the cerebral cortex, brain stem and hypothalamus. The changes of these amines are due to the inhibition of the activity of the enzymes responsible for their degradation, and to the facilitation of the transportation of neurotransmitters at brain level. (14).
In addition, Rhodiola prevents the release of catecholamines and the subsequent increase of cyclic AMP, as well as the depletion of adrenal catecholamines induced by acute stress. (15).
The adaptogenic activity of Rhodiola can also be due to the induction of the biosynthesis of opioid peptides and to the activation of the central and peripheral opioid receptors. (16-19).

IV. Materials and Methods.

Several cases of patients with diabetic peripheral neuropathy were reviewed to complete their descriptive analysis in a retrospective manner. These patients went to the Adaptógenos Medical Centers and Units all over the country, during the period between April 2002 and July 2004.
The information was obtained from the clinical histories of each one of the medical centers. Said information was entered into a database previously designed for the purpose of evaluating certain variables of clinical-therapeutical interest.
The study included all patients with a diagnosis of diabetic peripheral neuropathy of any sex, age and type of diabetes mellitus, who attended the Adaptógeno Medical Centers and Units, and who fulfilled the treatment proposed by Systemic Medicine during a period of six months.
All those clinical histories in which there was missing information of patients, in which the patient did not go back for subsequent appointments or in which the patient did not stick to the treatment were excluded. It is important to point out that most patients were prescribed the study of glycosylated Hb, however, only a small portion of them fulfilled this requirement; therefore, this criteria was not used to assess the evaluation. In addition, those diabetic patients with neuropathy and a diabetic foot complication were excluded from the study.
The following variables were analyzed:
1. Improvement in the symptoms typical of peripheral neuropathy related by patients.
2. Percentage of patients with undesirable side effects as a result of the treatment.
3. Tolerance to the treatment.
4. Changes in the quality of life of these patients.
The symptoms described by patients with peripheral Neuropathy were paresthesia, tingling, burning, sensation of sharp pain, cramps, numbness and sensation of pain or burning in the extremities, insensitivity to pain or changes in temperature, extreme sensitivity to the touch, loss of balance or coordination.
The changes in the quality of life were evaluated in accordance with the scale of measurement of quality of life by Grogono-Woodgate (20).

V. Results.

The total of patients with diabetic neuropathy included in this study is 135.
Distribution by Sex and Age.
77 females (57%) and 58 males (43%) were treated. Average age = 58 years old.
(Standard Deviation = 13 years).
Classification by type of diabetes:
From the 135 patients studied, 15 (11.1%) had type I Diabetes, and 120 (88.9%) had type II Diabetes.
Clinical Evolution:

From the 135 patients evaluated, 96 (71.1%) had improved the signs and symptoms typical of diabetic peripheral neuropathy (c 2 = 94.01).
The systemic formula used in this study is in the procedure of registration of intellectual property. For this reason, Adaptógeno Educational Medical Center has only mentioned 3 plants from the ones used in this disease, together with their scientific references. Any person who wants to know the complete systemic formula may formally request it to the institution.
(1) Superior plants are phytomedicines without side effects, according to Chinese tradition.
(2) The CMAs are medical centers with 8 or more doctors, while the UMAs have two doctors.

VI. Ref

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