Anamu, moringa, spirulina, and chlorella: contribution to the quality of life of oncology patients – results of the postmarketing prospective study performed in Serbia in 2021 – 2022

Introduction: The quality of life is one of the priority goals in the treatment of oncology patients. In addition to conventional therapies, symptomatic and supportive treatments are valuable for the final treatment outcome. Many such patients resort to alternative methods, such as herbal therapy.

Study aim: This prospective study aimed to assess the effect of the plants: anamu, moringa, spirulina, and chlorella, which are routinely used in Cuba, on the quality of life of oncology patients.

Materials and methods: Forty-six patients with various stage four malignant tumors were examined. Of the 46 patients, 26 were on chemotherapy, while 18 were on symptomatic and supportive therapy. The patients used extracts of the aforementioned plants orally, for three months. With prior consent and authorization, the standard EORTC QLQ-C30 questionnaire, written in the patients’ native language, was used to assess quality of life, before and after three months of use.

Results: According to patient ratings, overall assessment of patient general health status and quality of life showed significant improvement after three months of use of the extracts, as compared to the beginning of application. According to the questionnaire, all five parameters improved on the functional scale, (p < 0.001), and the scores on the symptoms scale also improved (fatigue, p = 0.015; pain, p = 0 ,044). Women achieved better physical functionality and significant loss of fatigue and pain, while cognitive functionality improved in men. Emotional functionality improved in the subgroup of patients who were receiving chemotherapy, while in those who had previously received chemotherapy, there were significant differences in the symptoms scale score regarding loss of appetite and constipation – symptoms that resolved after three months of product use, thus equating the subgroups in terms of the reduction of these symptoms. In other functional parameters, statistically significant differences were also obtained for all patients.

Conclusion: The improvement in the quality of life and functionality of patients, as well as the reduction in symptoms, whether the patients received chemotherapy or not, was statistically significant.

INTRODUCTION

Herbal medicine (phytotherapy) is the oldest form of treatment that uses plants and plant derivatives due to their medicinal properties [1].

The use of plants was the basis for the development of modern medicine, and in some rural and indigenous areas, they represent the only available means of treatment, due to the lack of medical facilities and resources for the application of modern medicine. In many communities, folk medicine has not yet disappeared. In addition to plant species that thrive in certain habitats, today there are opportunities to use plant species that do not grow in the area we live in. Therefore, we benefit from the use of medicinal plants (i.e., medicinal herbs), not only in the treatment of diseases, but also in the prevention of diseases and in nutrition [2].

In the 1990s, Professor Rosenberg, from the Department of Public Health at Harvard Medical School, citing the importance of integrative medicine, published two reports showing that 45% of American patients, after visiting their doctor, seek help from professionals in the field of what is often referred to as ‘alternative medicine’ [3], as an approach that is complementary to official medicine.

Integrative medicine represents a medical doctrine based on Hippocrates’ vision of the ‘art of healing’, which emphasizes the importance of treating the whole patient, i.e., applying a holistic approach to a person with health problems [4],[5]. The integrative model combines the knowledge of Western, science and technology based medicine (founded on scientific evidence), with certain therapeutic resources of what is known as ‘complementary medicine’, which includes the use of medicinal plants, as indicated by a professional, i.e., phytotherapy.

Integrative medicine is also very useful in the treatment of malignant diseases, when, at the same time, we want to preserve the patient’s quality of life [6],[7],[8]. Also, by applying the principles of integrative medicine, the fundamental role of appropriate nutrition in improving the general health status of patients is emphasized, which implies the creation of an individual nutrition program tailored to the patient’s disease [9].

Although, thus far, there is not enough evidence on the effectiveness of phytotherapy as the therapy of choice in the treatment of malignancies, there are indications that it can improve the quality of life. Phytotherapy can help patients with malignant diseases to cope with the side effects of therapy, as well as with some symptoms of malignant diseases. For example, the use of natural plant components in therapeutic concentrations, by adding orthomolecular supplementation, can help reduce the intake of traditional drugs (analgesics, anti-inflammatory drugs, anti-anxiety drugs, etc.) [6],[7],[8].

In Cuba, natural medicine uses phytotherapy as supplementary to conventional therapy in the treatment of chronic diseases, such as malignant diseases. Phytotherapy, as part of medical practice, uses professional experience to alleviate the symptoms of disease and the toxicity of conventional therapies. In a personalized approach to the treatment of patients with malignant tumors, standard medical practice, along with supportive therapy, leads to an improvement in the quality of life of patients, as well as an increase in the chances of recovery [10].

Phytotherapy, as a form of alternative therapy, helps to improve the function of the patient’s immune system by reducing oxidative stress, which slows down the progression of the disease, improves nutritional status, and promotes better tolerance to conventional therapies [11].

Among the plants that are used the most in Cuba for alternative cancer treatment, and which have been studied more closely, anamu, moringa, spirulina and chlorella stand out.

Anamu

Anamu or Petiveria alliacea L. (Phytolaccaceae) is an indigenous plant of the Amazon jungle and can also grow in areas such as tropical and Central America, the Caribbean and the southeastern part of the United States of America. It represents one of the plants with the greatest pharmacological potential in the world, as demonstrated by the fact that it was selected, at the University of Illinois, among 14,000 plant extracts, as one of 34 candidates with antitumor potential.Due to its numerous medicinal properties, it was studied in detail by the Pharmaceutical Laboratory in Cuba, where it was clarified that medicinal plants with therapeutic immunostimulating effects are not common in the plant kingdom. Anamu grows in abundance, both in the desert and in the cultivated areas of Cuba. It has proven effects in stimulating immune system cell response, which has justified the production of tablets made from the plant, and the registration of this supplement as a herbal immunostimulant, in accordance with the requirements of the Cuban regulatory authorities for the human use of drugs. The above-mentioned tablets contain a dose of powder made from the leaves and stems of the plant [10].

According to research conducted in Cuba by a team of scientists led by Dr. Zoe Lemus Rodríguez, anamu (the whole plant) contains numerous active ingredients, including the following: alkaloids (allantoin, N-methyl-4-trans methoxy proline); steroids (beta-sitosterol); triterpenes (isobornyl, isobornyl acetate, isobornyl cinnamate, alpha-friedelinol); sulfur derivatives (benzyl-2-hydroxy-5-ethyl-trisulfide, dibenzyl trisulfide); flavonoids (astilbin, gelatin, leridal, leridol, leridol-5-methyl-ether, myricitrin); inorganic compounds (potassium nitrate); lipids (lignoceric acid, lignoceryl lignocerate, linoleic acid, nonadecanoic acid, oleic acid, palmitic acid, stearic acid); benzene derivatives (benzaldehyde, benzoic acid); alkanes (lignoceryl alcohol); carbohydrates (pinitol). In particular, properties such as immunostimulation are attributed to tannins, polyphenols and benzyl-2-hydroxy-5-cetyl-trisulfide, which are found in the leaves and young stems of the plant [10],[11].

At the National Center for Scientific Research of Cuba, a study was conducted on anamu plant extracts which revealed the presence of elements such as selenium (Se), zinc (Zn), copper (Cu), iron (Fe) and magnesium (Mg), which affect the immune system [10].

In 1993, Jovićević demonstrated the inhibitory effect of anamu on tumor proliferation, especially in leukemia cell lines, without endangering healthy tissue [12].

Marini et al. described the effect of anamu plant extracts on the production of cytokines, such as interleukin-2 and interleukin-4, as well as on increasing the cytotoxic activity of natural killer cells (NK cells) [13].

In 1997, Williams reported that anamu increased the activity of the thymus and white blood cells. Other authors pointed out that the immunomodulatory effect is due to a significant increase in the phagocytic index of granulocytes in humans [14].

Recently, a test with an aqueous extract of this plant confirmed that it stimulates the production of lymphocytes and interleukin-2 in rats. A year later, in an experiment with mice, it was shown that the extract of anamu increases the activity of NK lymphocytes by 100%, and that it stimulates the production of interferon, interleukin-2 and interleukin-4 [14],[15],[16].

The latest findings on the action of tyrosine kinase inhibitors and molecular targets in oncology are currently linked to the investigation of the possibility of obtaining an antitumor pharmacological agent from this plant [17].

Moringa

Moringa (Moringa oleifera) is an evergreen tree and the best known and most widespread species in the Moringaceae family. Moringa leaves contain b-carotene, vitamin C, flavonoids, phenolic compounds, fatty acids, such as omega-3 and omega-6 fatty acids, as well as calcium and potassium. Its seeds have a high content of carbohydrates, lipids and proteins, which make up from 33% to 60% of its dry matter. This species is widely used for its preventive properties in chronic diseases (including antispasmodic, antidiuretic, antihypertensive, antiulcer, anticancerogenic, antidiabetic, antimicrobial, and antihypercholesterolemic properties) [18],[19],[20],[21],[22].

Protein isolates from this plant are used as food supplements and have the potential to generate bioactive peptides in vitro, by proteolysis or digestion. Peptides can be produced naturally by the gastrointestinal digestion process, but they can also be obtained in vitro, using proteolytic enzymes. The biofunctional properties of these peptides are related to regulatory functions in the cardiovascular, digestive, immune and nervous systems, depending on the composition and structure of amino acids. Moringa’s nutritional properties include antioxidant activity in the suppression of lipid peroxidation, antihypertensive function associated with the inhibition of angiotensin-converting enzyme (ACE), antidiabetic properties associated with amylase activity, anti-inflammatory properties, as well as the function of slowing cell aging, antimicrobial properties, and other [23],[24],[25],[26],[27].

Moringa oleifera contains a significant quantity of important phytochemicals, such as phenols, flavonoids, alkaloids, vitamins, glycosides, sterols, minerals and amino acids, in its seeds, leaves and fruit. Moringa seeds have been shown to have diuretic as well as antitumorous and antimicrobial properties. In 2005, a study was published that provided information on the cytotoxic effect of the ethanolic root extract of the Moringa oleifera plant on leukemia and melanoma cell lines. MCF7 is an estrogen-positive breast cancer cell line commonly used as an in vitro model in breast cancer therapeutic research [18],[28],[29],[30],[31],[32].

Moringa seeds contain dimeric cationic proteins (13-kDa), which is why they have coagulant and antimicrobial properties, and can be used for decontamination and treatment of turbid water. Moringa seeds contain 19% - 47% of essential oils, which are an excellent nutritional supplement. The seed oil is used not only as a vegetable oil for cooking, resistant to oxidative degradation, but also for the treatment of various nutritional intoxications [18],[33].

Spirulina and chlorella

Spirulina platensis (Sp) is a spiral-filamentous alga from the family of multicellular and photosynthetic cyanobacteria (blue-green algae) belonging to the class Cyanophyceae, the family Oscillatoriaceae. This cyanobacterium is cultivated worldwide and used as a primary dietary supplement. It contains a wide range of prophylactic and healing nutrients – vitamins, minerals, proteins, linoleic acid, b-carotene, as well as unexplored bioactive compounds. In addition to nutritional benefits, spirulina has other properties, such as antibacterial, antifungal, antiviral, anticancerous, anti-inflammatory and antioxidant properties, and is also used as a nutritional supplement in aquaculture and poultry farming [34].

Chlorella vulgaris (Cv) is a freshwater, green, unicellular microalga, belonging to the phylum Chlorophyta and recognized worldwide as a functional food product. It is rich in proteins, lipids, carotenoids, vitamins and minerals and is considered a valuable source of protein among potential food sources. It contains both omega-3 and omega-6 fatty acids, carbohydrates, cellulose, essential amino acids, carotenes and vitamin A. In addition, chlorella is used as a protein supplement for human consumption and as an alternative antibiotic in livestock production. Chlorella has also been confirmed to have immunomodulatory activity in chickens, improving growth performance and egg quality [35].

Among its active ingredients, Spirulina platensis contains minerals, vitamins, essential amino acids and proteins, as well as beta-carotene, tocopherols and phenolic acids, which have shown a high level of anti-inflammatory and antioxidant properties. This is why it is used as a supplement in human nutrition, as well as in the nutrition of many animal species, such as birds and fish. In addition, Spirulina platensis also contains a highly active ingredient, c-phycocyanin, which exhibits anti-inflammatory, immunomodulatory, hepatoprotective, nephroprotective, neuroprotective, antidiabetic, antigenotoxic, antihypertensive and anticancerous effects [34].

Spirulina is also rich in tetrapyrroles, which are directly linked to the bilirubin molecule, a powerful antioxidant and antiproliferative agent. The potential anticancerous effects of tetrapyrrole obtained from S. platensis are being investigated in pancreatic cancer. The antiproliferative effects of S. platensis and its tetrapyrrole components (phycocyanin (PCB) and chlorophyllin, a molecule that is a substitute for chlorophyll A) showed some activity in human pancreatic cancer cell lines and in nude mice with xenotransplanted cells [34].

STUDY AIM

The aim of the study was to assess the effect of the application of plant extracts from Cuba: anamu, moringa, spirulina, and chlorella, as dietary supplements, on the quality of life of oncology patients, during and after the application of oncology therapy.

MATERIALS AND METHODS

Fourty-six patients were included in the post-marketing prospective non-randomized study. Patients who agreed to fill out a questionnaire on quality of life before using herbal preparations were included. The extracts were previously registered in Serbia as a dietary supplement, and the patients received them as a donation from Cuban doctors. The study included patients suffering from various malignant tumors (nine patients with breast cancer, seven with lung cancer, six with colon cancer, five with prostate cancer, four with head and neck cancer, three with lymphoma, two with cervical cancer and one with ovarian cancer, two with stomach cancer, two with urinary tract cancer, two with brain cancer, two with soft tissue sarcoma, and one with pancreatic cancer). Of these patients, 20 were men and 26 were women, aged from 30 to 87 years, with the average age of 60. The patients underwent regular oncological follow-up, every three months, with their oncologist, in different oncological centers in Serbia.

There were 28 patients who received chemotherapy (10 men and 18 women), as well as 18 patients without chemotherapy (10 men and 8 women), (Table 1). The patients were in stage four of the disease.

Table 1. Respondent characteristics

With the approval of the European Organization for Research and Treatment of Cancer (EORTC), (Request ID: 89647), the standard EORTC QLQ-C30 questionnaire with 30 questions was used to assess quality of life [36]. The patients gave verbal consent and voluntarily filled out the questionnaire before starting to use the herbal preparations and after three months of use.

Preparations of herbal extracts of anamu, moringa and spirulina, plus chlorella, are individually encapsulated in three gelatin capsules of 400 mg, 500 mg and 500 mg, with a proportion of 80% spirulina and 20% chlorella. All patients confirmed compliance with the use of the preparation at home, after three months.

In keeping with the prescription for the preparation, during the first week the therapy was taken in the form of one capsule of each dietary supplement, in the morning only. In the second week, one capsule of each dietary supplement, in the morning and in the afternoon, was taken. In the third week, one capsule of each dietary supplement was taken, morning, afternoon and evening. From the fourth week onwards, patients took two capsules of each dietary supplement, in the morning, in the afternoon, and in the evening. Anamu was taken 15 minutes before a meal, and moringa and spirulina, during or after a meal.

The EORTC scoring system [37] and standard statistical methods – Wilcoxon test, chi-square test, and Fisher’s exact test, were used to process the obtained results, with the aim of determining a statistical significance, before and after the application of the preparation.

According to the scoring system, the questionnaire is divided into five functional scales, three symptoms scales, a global health status/quality of life scale, and six individual items (Table 2).

Table 2. EORTC QLQ-30 scoring system, Version 3.0

Higher score values on the functional scale, from 1 to 5, represent a high/healthier level of functioning. A higher score on the general health status scale, from 1 to 7, represents a better quality of life. On the other hand, a higher score on the symptoms scale, from 1 to 5, represents a more intense level of symptoms/problems.

RESULTS

The examined groups, according to gender and application of chemotherapy, did not differ in their characteristics, except for the fact that, before the application of therapy, women had slightly worse cognitive functions on the functional scale (result: 64.1 ± 31.51 vs. 44.17 ± 28.24, p = 0.027).

The assessment of patient global health status and quality of life, according to the results obtained, improved statistically significantly after three months of using the preparation (Graph 1).

Figure 1. Global health status and quality of life score, before and after the use of the preparation, in the entire group of respondents (N46) and in the subgroups, during chemotherapy (HT) (N28) and without ht (N18)

On the functional scale, statistically significant improvement was recorded for five parameters (Graph 2).

Figure 2. Functional scale score: physical (PF2), role (RF2), emotional (EF), cognitive (CF), and social (SF), before and after the use of the preparation (the whole group), (N46)

On the symptoms scale, a statistically significant improvement was noted in all parameters except for dyspnea and financial difficulties (Graph 3).

Figure 3. Symptoms scale: fatigue (F), nausea and vomiting (NV), pain (P), dyspnea (DY), sleeplessness (SL), loss of appetite (AP), constipation (CO), diarrhea (DI), and financial difficulties (FI), in the whole group (N46)

After using the preparation, women statistically achieved a slightly better result on the functional scale of physical functioning, while men achieved a slightly better result on the scale of cognitive functioning (Graph 4). On the symptoms scale, women had a more significant improvement regarding the sensation of fatigue and pain than men (Graph 5). There is a greater difference in the absolute score for fatigue, before and after the application of the preparation in women, which is also statistically significant (106.7 ± 15.88 vs. 97.44 ± 19.7, before, and 41.67 ± 17.24 vs. 27.78 ± 17, after).

Figure 4. lFunctional scale: physical functioning (PF2) and cognitive functioning (CF), Differences by sex, before and after therapy

Figure 5. lSymptoms scale: fatigue (FA), pain (PA), differences by sex, before and after thera

In the subgroup of patients who received chemotherapy, a statistically significant improvement in emotional functioning was achieved on the functional scale after the application of phytotherapy, and it was more significant than in the subgroup that did not receive chemotherapy (Graph 6). For other functionality parameters, for which a statistically significant difference was registered. (Graph 2), there was no difference between those patients who received chemotherapy and those who did not.

Figure 6. Functional scale: emotional (EF), in the group of patients who were on chemotherapy (N28) and in the group of patients who did not receive chemotherapy (N18) during the use of the preparation

In patients who received chemotherapy before starting on the preparation, there was a significant difference in the symptoms scale regarding the loss of appetite and constipation. This difference disappeared after three months of drug use and the subgroups were equal in terms of the reduction of these symptoms (Graph 7).

Figure 7. Symptoms scale scoring, loss of appetite (AP) and constipation (CO), in patients during chemotherapy (N28) and in patients who were not on chemotherapy (N18) during the use of the preparation

DISCUSSION

The study aimed to analyze the quality of life of patients with various malignant tumors, before and three months after the application of extracts from the plants anamu, moringa, spirulina and chlorella.

The most important results of this study show that, after three months of using the preparation, all functional parameters (physical, daily functioning, emotional, cognitive, and social functioning) improved significantly in patients, regardless of whether they received chemotherapy or not, and without gender differences.

According to trend research, more than 65% – 75% of patients with malignant diseases used some kind of complementary medicine [38], and according to World Health Organization data, this number is as high as 80% [39]. This is suggested to patients by family members, friends or someone who is already being treated for a malignancy.

In Serbia, the application of phytotherapy is still at a modest level. Serbian authors have shown that almost a third of patients believe that they can cure their disease with these methods, while the majority expect to achieve better treatment results with conventional methods than with alternative ones [40].

Complementary and alternative medicine are recognized treatment methods in many countries. These treatment methods include phytotherapy, which usually accounts for around 50% [41]. In the period between 1940 and 2014, more than half of the anticancer drugs that entered routine use were obtained from plants [39],[42].

Side effects of cytotoxic drugs significantly impair the quality of life during treatment. Among them, the most common are nausea and vomiting, loss of appetite, and weight loss [43]. In our study, patients receiving chemotherapy had significantly higher scores on the appetite loss scale than those not receiving chemotherapy. After three months of phytotherapy, there was a statistically significant reduction in 7 out of 9 symptoms on the symptoms scale, such as fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite and constipation. The most significant improvement was achieved for loss of appetite and constipation (Graph 7).

Minimal differences and slightly better effects in women, on the physical functionality scale, as well as for pain and fatigue, on the symptoms scale, can be explained by the greater general vulnerability of the female population.

Improvement in emotional functionality in chemotherapy patients is particularly significant, as it boosts morale and the desire to fight the disease.

Analysis of the symptoms scale before the use of herbal preparations shows that there is a significant difference, in terms of more pronounced symptomatology, in patients who received chemotherapy, as compared to those who did not, which was to be expected. After three months of preparation use, these differences among patients disappeared, with a significant improvement and reduction in 7 out of 9 of the assessed symptoms.

The idea of herbal medicine complementing conventional commercial treatment is becoming increasingly popular, as it could overcome financial difficulties as well as health problems caused by modern treatments. Herbal medicines would be cheaper, making them more accessible to people in rural and poor areas. These drugs would have fewer side effects and therefore improve the patient’s quality of life during treatment [44]. The combination of several plant components should have a greater potential and more effects on the disease than a single plant, as a consequence of the synergistic effect of its components [45]. There is evidence that numerous active components of various herbal mixtures act on malignant cells and other diseases. In addition, they are suitable for overcoming resistance to therapies because they act on different targets [46].

Although it is known that the combination of chemotherapy drugs and bioactive substances from medicinal plants can have anticancerous effects, while reducing side effects [47], our study could not analyze the possible anticancerous effects of anamu, spirulina, chlorella, and moringa, which have been described in literature dealing with the use of these plants [20],[40], due to the small number of subjects and the heterogeneous group of malignancies that were treated with different methods. The results of this study refer only to anamu, moringa, spirulina and chlorella and cannot be applied to other medicinal plants. According to the World Health Organization, out of 2,500,000 species of plants, 80,000 have therapeutic properties and about 21,000 have the potential to be used as medicinal plants [40].

Given that preparations of plant extracts are registered in Serbia and are available to all oncology patients, they can be used as a supplement in supportive and symptomatic therapy, with the aim of improving the quality of life in patients.

Although the study was conducted on a small number of subjects and is heterogeneous in terms of tumor pathology, it provides information on the effects of Cuban herbal preparations for which there is not much information in medical professional journals. This indicates the need for additional research on a larger number of subjects and in relation to specific tumors.

CONCLUSION

According to the obtained respondent answers, the overall assessment of the global health status and quality of life of the patients showed that they improved significantly, which indicates the benefit of consuming nutritional supplements made from the plants anamu, moringa, spirulina and chlorella, for the quality of life and for reducing the symptoms in oncology patients.

The improvements described are present both in patients with diagnosed disease who did not receive conventional therapy and in patients who received chemotherapy.