Benefits of a Food Supplement Containing Boswellia serrata and Bromelain for Improving the Quality of Life in Patients with Osteoarthritis: A Pilot Study

Abstract

Background:

Osteoarthritis (OA) is a joint disease involving articular cartilage degeneration causing patients pain, joint stiffness, physical disability, and significantly reducing their quality of life (QoL).

Purpose:

The aim of this study was to assess whether the daily consumption of a gastroresistant food supplement formulation containing a combination of Boswellia serrata and bromelain could improve the QoL of patients suffering from various forms of OA.

Materials and Methods:

Forty-nine patients were enrolled in this pilot study conducted from June 2015 to October 2016. Patients took a Boswellia- and bromelain-based supplement for a period between 1 and 6 months. At baseline and at the end of the study, patients completed a self-assessment QoL questionnaire regarding their independence in performing daily activities. QoL scores were compared between baseline and follow-up by means of the Wilcoxon signed-rank test in all patients and in the subgroups of patients with knee, hip, or generalized OA.

Results:

Forty-nine patients, 6 men and 43 women, aged between 23 and 92 years, (mean age 63.24) participated in the study. At follow-up (3.0 ± 0.7 months), a significant improvement was observed for 7 of 10 QoL questions and, overall, for the total QoL score. The most significant improvements were observed in the joints that were more strongly affected at baseline. A similar trend was observed when separately considering patients with knee, hip, or generalized OA. No patients experienced adverse events and no drug interactions were reported.

Conclusions:

From this pilot study, it emerges that the use of the gastroresistant formulation containing the combination of Boswellia and bromelain supplements can represent a valuable nonpharmacological tool for improving the QoL of patients suffering from different forms of OA. Further studies should be conducted to confirm this first evidence.

Introduction

Osteoarthritis (OA) is a degenerative disease of the joints, mainly affecting the articular cartilage. It is the most common form of arthritis in Western countries, and it is estimated that 9.6% of men and 18.0% of women aged over 60 years suffer from symptomatic OA worldwide.¹ The number of people affected by OA is likely to increase due to the aging of the population and the obesity epidemic.²

OA mostly affects the joints that have been continually stressed throughout the years, including the knees, hips, fingers, and the lower spine region.^1,3 OA of the knee is probably the most studied, even if the highest OA prevalence is found in hand joints. OA of the knee tends to be more prevalent in women than in men, whereas no gender differences were found in hip and hand OA.⁴ Noteworthy, individuals who develop symptomatic OA in one joint are more predisposed to have generalized OA, defined as OA involving multiple joints.⁵

Recognized risk factors for disease development include age, female sex, genetic factors, obesity, joint biomechanics, repetitive joint use, joint injury, and joint malalignment.⁵

The cardinal clinical symptoms are pain and functional impairment such as joint stiffness and physical disability, which may ultimately significantly impair the quality of life (QoL).^6
–8

Pharmacological therapies typically consist of the use of paracetamol and nonsteroidal anti-inflammatory drugs.^9,10 Corticosteroids and opioids can also be used. However, prolonged pharmacological treatment has limited efficacy and may be associated with considerable toxicity, resulting in gastrointestinal or cardiovascular complications.^5,11,12 Nonpharmacological strategies for OA treatment include exercise, physiotherapy, weight loss, and physical aids.^5,13,14 In addition, in the last years, dietary supplements are gaining a lot of attention due to their generally low rate of side effects and adverse reactions.^15

–18

In this perspective, extracts of Boswellia serrata and bromelain were considered because they were reported to have beneficial effects in different forms of inflammatory conditions.^1,19
–21

B. serrata is one of the best recognized, herbal extract treatments for OA, which has been shown to improve physical function in patients with knee OA.^22

–26

Current evidence also indicates that the use of bromelain, an extract derived from the pineapple plant, can be beneficial in the treatment of pain and stiffness in patients with knee OA.^27

–31 A previous study has shown that administration of an oral preparation combining bromelain, trypsin, and rutoside improved OA symptoms in patients with knee OA,³² whereas other studies report a lack of effectiveness of bromelain in shoulder OA.^19,33

With regard to the mechanism of action, B. serrata used since ancient times³⁴ contains different boswellic acids, such as beta-boswellic acid, keto-beta-boswellic acid, and acetyl-keto-beta-boswellic acid (AKBA). AKBA has been reported to inhibit the lipoxygenase pathway and to have appreciable anti-inflammatory effects.^35,36 A number of studies have now shown that supplements containing B. serrata exhibit clinically relevant effects on pain, stiffness, and physical function in patients suffering from knee OA.^{1,22

–26,37}

Bromelain is a crude extract of pineapple plant (Ananas comosus), containing a mixture of proteolytic enzymes that exhibit anti-inflammatory and analgesic properties.^19,20,38,39 Due to these properties, bromelain has been indicated as a valuable supplement in multiple medical fields, mainly for surgical wounds, inflammation due to trauma and surgery, and debridement of deep burns.^39,40 In addition, there is evidence suggesting its effectiveness in OA. Bromelain was first used in patients with rheumatoid arthritis and OA in 1964.⁴¹ It has been reported to decrease pain and stiffness also in patients with knee OA,^27

–31 with an activity comparable or superior to diclofenac.^42,43

Recently, the food supplement EVAN^®, containing B. serrata and bromelain extracts, has been placed on the market.

The EVAN supplement can be provided as orosoluble sachets or as gastroresistant lipid matrix tablets obtained through a novel patented technology that gives gastric protection to the central layer of the tablet, which results in a prolonged and gradual release of the active principles. To the authors' knowledge, no data are available in the literature regarding the clinical use of this supplement for the treatment of OA symptoms.

The aim of this pilot study was to assess the safety and effectiveness of a formulation containing B. serrata and bromelain in improving the QoL of patients with different forms of OA. For this purpose, the performance of daily activities was evaluated using a simplified, patient self-report questionnaire designed to be suitable in an outpatient setting for different types of OA.

Materials and Methods

Study design

The present study was a prospective pilot study of patients attending the rheumatology outpatient clinic of S. Anna e Sebastiano Hospital of Caserta (Italy) from June 2015 to October 2016.

Patients

Patients above the age of 18 years of either gender presenting with clinical signs of either generalized or localized unilateral or bilateral OA were invited to participate in the study. For inclusion, patients had to exhibit mild-to-moderate joint pain according to a 10-point numerical rating scale (NRS) of joint pain, with 0 representing no pain and 10 representing extreme pain (for inclusion, the NRS score had to be between 0 and 6). For knee OA, only patients with mild or moderate OA according to the Kellgren and Lawrence criteria⁴⁴ (grade 2 or 3) were included.

Patients were excluded from the study if they had previously started treatment with symptomatic slow-acting drugs for OA, if they had known hypersensitivity to the investigational product, or if they received intra-articular injections of hyaluronic acid within 3 months before enrollment. Pregnant or lactating women were excluded from the study. Patients suffering from severe knee OA (Kellgren and Lawrence grade 4) and severe pain (NRS score between 6 and 10) were also excluded from the study.

Patients were duly informed before enrollment about the purpose of the study and signed an informed consent related to the confidentiality of personal data collected.

Treatment

The food supplement (EVAN; Biohealth S.r.l, Turin, Italy) was provided as 990-mg tablets. Each tablet contains 750 mg of B. serrata extract and 80 mg of pineapple stem, source of bromelain. The B. serrata extract was obtained from the gum resin part of the plant using as extraction solvent of 100% ethyl acetate; the herb extract ratio was 10:1. The extract is titrated at 65% in boswellic acids. Bromelain was obtained as a dry powder from the stem of the pineapple plant, with a proteolytic enzymatic activity equal to 250 GDU (gelatin digesting units)/g.

Tablets were manufactured according to a patented technology (T-MatrixLipid™; Truffini & Reggè, Milan, Italy) that allows prolonged and gradual release of the active principles; the ingredients are coated in a lipid matrix obtained with excipients produced by chemical synthesis and not normally present in the mammalian organism to obtain gastroresistant tablets (European Patent EP 1225876B1).

Patients took two tablets a day for 1–6 months.

Patients were monitored at the first recruitment visit (T0) and at the end of the treatment, which was scheduled to last between 1 and 6 months, at the outpatient follow-up visit (T1).

Data collection

At T0, eligible patients were asked to provide the following information: age, sex, height, weight, medical condition of interest, presence of previous fractures, concomitant medical conditions, smoking habits, medications prescribed during the study, and menopausal status. At T1, patients were asked to report any adverse effects or complications.

Answers to QoL questionnaires were collected at both T0 and T1. The QoL patient self-report questionnaire was developed as a shortened simplified version of the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire (section C: difficulty in performing daily activities), modified to be applicable in an outpatient context and for subjects with different forms of OA. The questionnaire comprises 10 questions evaluating the patient's degree of difficulty in performance of everyday tasks without assistance. Patients were asked to rate their current health status on a five-point scale (none, mild, moderate, severe, and extreme; coded 0 to 4).

Statistical analysis

Demographic characteristics and anamnestic data were analyzed using descriptive statistical techniques. Continuous variables were summarized using mean, standard deviation, range, median, and interquartile range; categorical variables were described by counts and percentages.

Difficulty in performing the assessed tasks based on the self-report was categorized into five grades. To investigate whether the treatment was effective, changes in the scores for the activities assessed in the self-reported questionnaires between T0 and T1 were analyzed using the Wilcoxon signed-rank test.

The significance level was set at 0.05. Statistical calculations were performed using standard statistical software (Origin 9.0; OriginLab Co, Northampton, MA).

Results

Patient characteristics

Patient characteristics are shown in Table 1. The study population included 49 patients, 6 men and 43 women, with a mean age of 63.2 ± 12.3 years (range between 23 and 92 years). Their body weight ranged between 57 and 90 kg (mean 70.5 kg) and their height from 150 to 180 cm (mean 162.9 cm). At the time of enrollment, 40 patients were taking medications (Table 1) that were maintained throughout the study.

Table 1.

Patient Characteristics

Characteristic	n/mean ± standard deviation
Sex (male/female)	6/43
Menopausal status	Premenopausal: 7/43; postmenopausal: 36/43
Smoker	Current smoker: 14; nonsmoker: 30; former smoker: 5
Age (years)	63.24 ± 12.31
Body weight (kg)	70.49 ± 8.61
Height (cm)	162.90 ± 7.17 cm
Previous fractures	Yes: 4; No: 45
Medical condition of interest	Knee OA: 20 (40.82%; 8/20 bilateral); hip OA: 14 (28.57%; 6/14 bilateral); generalized OA: 11 (22.45%); hand OA: 2 (4.08%); rhizarthrosis: 1 (2.04%); spondylosis: 1 (2.04%)
Concomitant medical conditions	None: 7 (14.29%); other arthropathy: 19 (38.78%); diabetes: 12 (24.45%); osteoporosis: 6 (12.24%); chronic obstructive pulmonary disease: 2 (4.08%); asthma: 3 (6.12%); liver disease: 1 (2.04%); stomach pain: 13 (26.53%)
Concomitant medications	None: 9 (18.37%); cortisone/NSAIDs: 14 (28.57%); antiasthmatic drugs; 7 (14.28%); antacids: 5 (10.20%); bisphosphonates: 3 (6.12%); insulin: 5 (10.20%); metmorfin: 5 (10.20%); lyrica: 1 (2.04%); statins: 1 (2.04%); diuretics: 1 (2.04%); oxycodone/naloxone: 1 (2.04%)

NSAIDs, nonsteroidal anti-inflammatory drugs; OA, osteoarthritis.

All patients suffered from different types of OA. Six patients suffered from osteoporosis. The most affected body parts were the knee (20 patients) and the hip (14 patients); 11 patients presented generalized OA, and in the four remaining cases, a different body part (2 for hand, 1 base of the thumb, and 1 spine) was affected.

Forty-two subjects presented one (35 patients) or more (7 patients) concomitant conditions, comprising joint pathologies other than OA (19 patients), stomach pain (13), diabetes (12), asthma (3), chronic obstructive pulmonary disease (2), and liver disease (1).

All patients took two tablets per day of the Boswellia- and bromelain-based supplement; the duration of treatment with EVAN was 3.0 ± 0.7 months (range, 1.0–5.9 months). During the study, patients were allowed to take medications either for joint pain or for other medical conditions.

Clinical efficacy

All patients provided their answers to the QoL questionnaires and scores were compared between T0 and T1. A significant improvement was observed for 7 of the 10 items assessed and overall when considering the total QoL score (p < 0.001, Wilcoxon signed-rank test) (Table 2). The three items for which no differences were observed between T0 and T1 concern the questions where most patients scored better at baseline (score equal to 0 or 1 in >95% of subjects): feeding, preparing breakfast and lunch, and mobility at home. On the contrary, the domains where a significant improvement was observed were those that were more impacted before the study (getting washed and dressed, foot care, sitting down in a chair, stair climbing, walking outside, and performing light and heavy tasks). Total QoL score distribution at T0 and T1 is shown in Figure 1.

FIG. 1.

Total QoL scores at T0 and T1 in all patients (A) and in the groups of patients with knee (B), hip (C), or generalized (D) OA. Score: 0, the patient can perform the task without any difficulty and without help; 1, the patient can perform the task without some difficulty and without help; 2, the patient can perform the task with great difficulty and without help; 3, the patient can perform the task only if helped by another person; and 4, the patient is completely unable to perform the task. QoL, quality of life; OA, osteoarthritis.

Table 2.

Comparison of Quality-of-Life Scores (Mean ± Standard Deviation) Between T0 and T1 in All Patients and in the Groups of Patients with Knee, Hip, or Generalized Osteoarthritis

Physical function assessment (difficulty for performing the task without assistance)	Group
	All patients	Knee OA	Hip OA	Generalized OA
Getting washed and dressed
T0	0.55 ± 0.58	0.65 ± 0.67	0.29 ± 0.47	0.64 ± 0.50
T1	0.16 ± 0.37	0.2 ± 0.41	0 ± 0	0.28 ± 0.47
p	<0.001	<0.01	0.072	0.072
Putting on and taking off your socks or panty hose or stockings (foot care)
T0	1.57 ± 1.22	1.7 ± 1.30	2.21 ± 1.25	1 ± 0.45
T1	0.65 ± 0.69	0.8 ± 0.77	0.86 ± 0.66	0.37 ± 0.50
p	<0.001	<0.001	<0.01	<0.05
Feeding
T0	0.18 ± 0.39	0.1 ± 0.31	0 ± 0	0.36 ± 0.50
T1	0.12 ± 0.33	0.1 ± 0.31	0 ± 0	0.18 ± 0.40
p	0.250	1	1	0.346
Cooking
T0	0.26 ± 0.53	0.35 ± 0.59	0 ± 0	0.18 ± 0.40
T1	0.18 ± 0.39	0.25 ± 0.44	0 ± 0	0.27 ± 0.47
p	0.312	1	1	1
Sitting down in a chair and standing up
T0	0.75 ± 0.69	1.05 ± 0.76	0.43 ± 0.51	0.82 ± 0.60
T1	0.18 ± 0.39	0.3 ± 0.47	0 ± 0	0.27 ± 0.47
p	<0.001	<0.001	<0.05	<0.05
Moving around the house (also using walking aids)
T0	0.24 ± 0.43	0.3 ± 0.47	0.14 ± 0.36	0.27 ± 0.47
T1	0.16 ± 0.37	0.25 ± 0.44	0 ± 0	0.18 ± 0.40
p	0.125	1	0.5	1
Descending and ascending stairs
T0	0.98 ± 0.80	1.3 ± 0.80	0.64 ± 0.63	1.09 ± 0.83
T1	0.28 ± 0.5	0.4 ± 0.50	0.14 ± 0.53	0.36 ± 0.50
p	<0.001	<0.001	<0.01	<0.01
Walking outside
T0	0.88 ± 0.81	1.1 ± 0.91	0.5 ± 0.52	1.09 ± 0.83
T1	0.35 ± 0.56	0.55 ± 0.60	0 ± 0	0.45 ± 0.69
p	<0.001	<0.01	<0.01	<0.05
Light domestic duties
T0	0.55 ± 0.76	0.8 ± 1.00	0.21 ± 0.42	0.46 ± 0.52
T1	0.29 ± 0.50	0.35 ± 0.59	0.07 ± 0.27	0.27 ± 0.47
p	<0.001	<0.01	<0.05	0.5
Heavy domestic duties
T0	1.98 ± 1.16	2.4 ± 0.99	1.71 ± 1.38	1.63 ± 1.21
T1	0.86 ± 0.84	1.25 ± 0.85	0.71 ± 0.82	0.45 ± 0.69
p	<0.001	<0.001	<0.01	<0.01
Total QoL score
T0	0.80 ± 0.96	0.98 ± 1.05	0.61 ± 0.99	0.75 ± 0.78
T1	0.32 ± 0.56	0.44 ± 0.64	0.18 ± 0.48	0.31 ± 0.50
p	<0.001	<0.001	<0.001	<0.001

Wilcoxon signed-rank test was applied for all comparisons. Significant values are highlighted in italics.

QoL, quality of life; OA, osteoarthritis.

A similar trend in physical function improvement was observed when assessing QoL changes between T0 and T1 in the groups of individuals suffering from knee (20 patients), hip (14 patients), or generalized (11 patients) OA. The total QoL score and the scores of most items were significantly better at T1 in all the three groups of patients (Table 2). All three individual groups improved their capability of feeding, preparing breakfast and lunch, and mobility at home. Differently, the ability of patients in getting dressed and in washing was not improved in the hip and generalized OA groups at T1, while an improvement for these tasks was seen in the knee group and when considering all patients.

Overall, it can be concluded that the capability of patients in conducting everyday tasks without difficulties was improved after treatment with EVAN.

Product tolerability

No patients experienced adverse events and no drug interactions were reported during the study, indicating that the treatment with EVAN was well tolerated.

Discussion

The aim of this study was to perform a pilot investigation of the clinical effectiveness of a novel supplement containing B. serrata and bromelain (EVAN), in the form of tablets ensuring a prolonged and gradual release of active principles, in patients with OA of different forms (mostly knee, hip, and generalized OA).

OA is among the diseases with the fastest growing rate of incidence, mainly due to the increasing age of the population.^1,5 Clinical data on the use of food supplements in OA are available, the treatment outcomes in trials testing the efficacy of food supplements in OA remain dependent upon the product tested and mostly upon the extracts contained, their concentrations, and their bioavailability. Thus, it is important to research ad hoc evidence when assessing the validity of a food supplement.

In this study, 49 patients with different forms of OA (mostly knee, hip, and generalized OA) provided answers to specific questions related to their autonomy in performing everyday activities at the end of a treatment period with the food supplement. At follow-up (3 ± 0.7 months), patients reported an improvement in their autonomy in performing most of the tasks assessed. The improvement was significant for daily activities that were mostly impaired at baseline, while nonsignificant changes were observed for less-demanding activities, for which patients were already performing well before the treatment. This was true when considering all the study groups and also when assessing separately the groups of patients affected by a specific OA type. This preliminary evidence is important considering that for both Boswellia and bromelain extracts, and for food supplements in general, there is a lack of studies on their effectiveness and safety in OA types other than knee OA.

Patients enrolled in this study were allowed to take other medications (either for joint pain or for other medical conditions), and neither side effects associated with the food supplement nor drug interactions were reported in any patient.

With regard to the mechanisms of action, α- and β-boswellic acids and other pentacyclic triterpenic acids, which are the main pharmacologically active ingredients of B. serrata, have been shown to inhibit proinflammatory processes by their effects on 5-lipooxygenase, cyclo-oxygenase, and complement system.⁴⁵

With regard to bromelain, it represents the combination of thiol proteases available in the extract of A. comosus. Experimental evidence indicated that the anti-inflammatory effect of bromelain is mediated by several factors. These include the increase of serum fibrinolytic activity, reduction of plasma fibrinogen levels, and decrease of bradykinin levels, which in turn reduces vascular permeability and edema. Finally, reduction of PGE2 and thromboxane A2 has also been reported.¹⁹

Because of its fibrinolytic property, bromelain has been shown to reduce pannus formation in patients with rheumatoid arthritis, thus emerging as a promising tool for the prevention of disease progression.⁴⁶

The two ingredients therefore act with different mechanisms and interfere with different pathways of the inflammatory process and development of musculoskeletal dysfunction. For this reason, it is likely that they can display relevant synergistic activity in reducing inflammation and dysfunction associated with OA.

The formulation used in this study, which combines the two ingredients in a gastroresistant and prolonged release formulation, may exert a more powerful effect on clinical manifestations of OA in its different forms compared with the individual herbal extracts.

The results of this pilot study strongly support the potential of using the combination of the two ingredients to potentiate their therapeutic efficacy in the treatment of OA, not limited only to the knee but also to other sites and in generalized OA.

The study provides a first evidence of the clinical efficacy and tolerability of a product that has recently been placed on the market and for which no clinical data are available yet. This preliminary analysis suggests that further controlled prospective studies should be conducted to investigate the usefulness of these extracts in OA and whether the technology allowing their prolonged and gradual release played an important role in determining their efficacy.

Conclusions

The treatment with the food supplement containing the combination of Boswellia and bromelain supplied in the form of gastroresistant tablets was beneficial in improving the independence (in conducting daily activities) of patients with various forms of OA. Further studies in a larger cohort of patients and trials assessing the QoL according to validated questionnaires could finally confirm the results of the present pilot study.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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