PMA - Zeolite (Clinoptilolite) in the Management of Irritable Bowel Syndrome - a Non-Interventional Study.

In clinical practice, the treatment of patients with irritable bowel syndrome (IBS) can be very challenging. The aims of the present non-interventional study (NIS) were to investigate the tolerability and efficacy of PMA-zeolite under everyday conditions in patients with diarrheic IBS type (IBS-D) or constipated type (IBS-C) or mixed type (IBS-M). METHODS: To document prospective data on tolerability and symptom frequency in the frame of a nationwide NIS, we recruited 204 IBS patients. The study focused on the IBS-related quality of life (measured by the SF-36 questionnaire) and improvements of IBS-related symptoms according to specific ROM-III criteria and stool consistency (Bristol stool scale). The participants documented their abdominal pain, bloating, number of bowel movements, and stool consistency through a web-based internet platform (initial and exit questionnaires) and daily diary entries over the period of intake (8 weeks). RESULTS: A total of 82.2% of the recruited patients had filled in the questionnaires before and after the 8-week treatment with PMA-zeolite. Seven of the eight subscales of the SF-36 improved significantly (p<0,001); the reduction in abdominal pain was especially significant (p<0,001). The diary entries confirmed the reduction in abdominal pain and revealed a significant reduction in days with bloating (p<0,001). The Bristol-stool-scale analysis showed improvements; particularly, patients with IBS-D benefited from the treatment (p<0,001). CONCLUSION: The treatment duration of 8 weeks was well tolerated by most patients. Under everyday life conditions, PMA-zeolite alleviated the global IBS-related symptoms and raised the quality of life (QOL). The PMA-zeolite, thus, may represent a good adjuvant therapeutic option for patients with irritable bowel syndrome.

Survival analyses of the ZeOxaNMulti trial: Follow-up randomized, double-blinded, placebo-controlled trial of oral PMA-zeolite to prevent chemotherapy-induced side effects, especially peripheral neuropathy.

Following the previously published results of the clinical randomized ZeOxaNMulti trial, we evaluated the potential of the tested product PMA-ZEO (Multizeo Med) in the prevention of chemotherapy-induced side effects (especially peripheral neuropathy) within a 30-month follow-up analysis. The aim was to determine the disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) in a study-population suffering from colorectal cancer that was previously enrolled in the ZeOxaNMulti trial from April 2015 to October 2018. The participants of the study were randomized to receive either PMA-ZEO or placebo while undergoing oxaliplatin-based chemotherapy. A total of 104 patients (pts) (51% of participants randomized to the PMA-ZEO group and 49% to the placebo group), out of a total of 120 pts included in the ZeOxaNMulti trial in 2015, were followed up until March 2021 and were included in the follow-up analysis. According to the chemotherapy line, 44.2% of patients received chemotherapy in an adjuvant setting, and 55.8% of patients received chemotherapy as first-line treatment. The statistical analysis for DFS, PFS, and OS was performed by comparison of the end results with data from the PMA-ZEO/placebo-intervention start point. The analysis of OS did not show statistically significant differences in the first-line chemotherapy patients randomized to PMA-ZEO than among the placebo group (p = 0.1) over the whole period of follow-up (30 months). However, focusing on the PMA-ZEO supplementation time point (7 months), a positive and statistically significant trend (p = 0.004) was documented in the OS analysis for the first-line chemotherapy patients with increasing months of PMA-ZEO treatment compared to the placebo group. Furthermore, borderline statistical significance was reached for PFS at the PMA-ZEO supplementation time point (7 months) in the first-line chemotherapy patients (p = 0.05) for cancer progression events. After stratification of the first-line chemotherapy patients, statistically relevant trends for OS for age, comorbidities, and oxaliplatin dosage (cycles) were also determined. The overall results for DFS (adjuvant patients), PFS (first-line chemotherapy patients), and OS (adjuvant and first-line chemotherapy patients) were generally slightly better in the PMA-ZEO group than in the placebo group, even though no statistically significant results were obtained between the groups within the follow-up period until 2021 (30 months). Based on this follow-up analysis, protective effects of PMA-zeolite supplementation can be deduced. A positive trend and more importantly, significant results in PFS and OS for specific patient groups during and/or after PMA-ZEO treatment were determined, which supports the use of PMA-ZEO as an oncological supportive therapy.

Clinical Parameters in Osteoporosis Patients Supplemented With PMA-Zeolite at the End of 5-Year Double-Blinded Clinical Trial.

Osteoporosis is among the most common pathologies. Associated complications in osteoporotic patients, in particular hip fractures and vertebral fractures, cause disabilities and significant quality of life deterioration. Standard treatment of osteoporosis, based on pharmacotherapy does still not yield adequate results, and the problem of osteoporosis remains incompletely solved. Additionally, adverse drug events and fractures after long-termed pharmacotherapy pose additional challenges within designing a proper therapy regimen. Improved clinical approach and new synergistic treatment modalities are consequently still needed. The rationale of the presented study was accordingly, to expand our preclinical animal study on human patients with osteoporosis, based on positive effects on bones observed in animals with osteopenia treated with PMA-zeolite. We specifically monitored effects of PMA-zeolite on the bone quality parameters, fracture risk and quality of life in a cohort of initially recruited 100 osteoporosis patients during a follow-up period of 5 years within a randomized, placebo-controlled and double blinded clinical study (TOP study). Obtained results provide evidence on the PMA-zeolite positive effects on the bone strength of osteoporotic patients as the risk of fractures was significantly decreased in PMA-zeolite-treated patients with respect to time before entering the study (p = 0.002). Statistical evidence point also to positive bone changes in the 5-years TOP study course as evidenced through osteocalcin and beta-cross laps values showing a prevalence of the bone-formation process (p < 0.05). BMD values were not significantly affected after the 5-years follow-up in PMA-zeolite-treated patients in comparison with the Placebo group. Results support the initial expectations based on our previously published preclinical studies on clinoptilolite product PMA-zeolite in animals that could be a new therapeutic option in osteoporosis patients.

Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients.

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis. Clinical Trial Registration: [https://clinicaltrials.gov], identifiers [NCT03901989, NCT05178719, NCT04370535, NCT04607018].

PMA-zeolite can modulate inflammation associated markers in irritable bowel disease - an explorative randomized, double blinded, controlled pilot trial.

OBJECTIVES: Preclinical and clinical data suggest, that the microporous mineral with large inner surface and ion exchanger capability PMA-(Panaceo-micro-activation)-zeolite can bind irritating and inflammation associated chime-constituents. We hypothesised whether or not it can ameliorate subclinical inflammation, and investigated the potential in the management of patients with Irritable Bowel syndrome (IBS). METHODS: The trial design was prospective, randomized, controlled, double-blinded, pilot study with 41 patients. They received orally 3 g of the medicinal product PMA-zeolite or microcrystalline cellulose (control) twice a day. At baseline and after three months the symptom load, blood and stool parameters, like high sensitivity C-reactive protein (hsCRP), zonulin, α1-antitrypsin, interleukin IL-10, and changes in the gut microbiome were determined by means of ANOVA, ANCOVA and non parametric statistical analyses. RESULTS: The IBS-associated symptom scores decreased significantly in both groups (p=0,001) indicating a strong placebo effect. In the verum but not in the placebo group various inflammation related laboratory parameters decreased. The gross statistical comparison revealed a reduction of α1-antitrypsin significant (p=0,037), a lowered inflammation marker hsCRP, paralleled specific microbiome changes (Lactobacillus, Bifidobacteria, and Firmicutes). CONCLUSIONS: The decrease of blood hsCRP and decreased stool α1-antitrypsin suggest that PMA-zeolite possibly can lower inflammation in the gut of IBS patients. The corresponding increase of the immune modulating species Bifidobacteria and Lactobacillus and the reduction of Firmicutes also point at an inflammation ameliorating effect and a possible mucous layer strengthening effect. The protocol of this explorative pilot study is feasible for a sufficiently powered trial on inflammation amelioration in IBS patients.

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial.

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

ZeOxaNMulti Trial: A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral PMA-zeolite to prevent Chemotherapy-Induced Side Effects, in particular, Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium - recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.

Nutrient composition of selected indigenous fruits from sub-Saharan Africa.

Indigenous fruits constitute an important part of human diets in many sub-Saharan African countries, particularly in rural areas and during droughts. In order to promote and expand the utilisation of these fruits, knowledge on their nutritional composition is essential. This review presents the results of a literature research of the nutritional composition of ten selected indigenous fruits from sub-Saharan Africa. Species were selected based on their current importance as well as their future potential for nutrition, processing and cash income generation. Compositional data were compiled and mean values of components per species were calculated. Most papers were compiled for Adansonia digitata (26) and Dacryodes edulis (16), followed by Tamarindus indica (ten), Balanites aegyptiaca (nine), Sclerocarya birrea (nine), Ziziphus mauritiana (nine), Vitex doniana (seven) and Irvingia gabonensis (five), and least for Uapaca kirkiana (three) and Syzygium guineense (three). Fruits were found to be mainly analysed for macronutrients and minerals. Vitamins, apart from vitamin C, were rarely reported. Substantial compositional differences were found among as well as within the different fruit species. The results of this study emphasise the need to generate more high-quality data on a wider spectrum of components of the selected indigenous fruits in sub-Saharan Africa.

FAO/INFOODS food composition database for biodiversity.

Nutrient content can vary as much between different varieties of the same foods, as they do among different foods. Knowledge of varietal differences can therefore mean the difference between nutrient adequacy and inadequacy. The FAO/INFOODS food composition database for biodiversity has been developed with analytical data for foods described at the level of variety, cultivar and breed, and for underutilized and wild foods. It contains 6411 food entries and values for 451 components together with the bibliographic references and other information. The database is in MS Excel format and can be downloaded free-of-charge from the INFOODS website http://www.fao.org/infoods/biodiversity/index_en.stm. It is intended to annually publish new editions, making these data available for national and regional food composition databases. This database could be used to raise the awareness, promote and investigate food biodiversity and help to better estimate nutrient intakes.