# Recent Advances and Insights into Bromelain Processing, Pharmacokinetics and Therapeutic Uses
## 6 Bromelain Studies
### Other Applications  
Bromelain is also an interesting nutraceuticaltical for cosmetic dental applications, in particular for tooth whitening. In a recent study, tooth bleaching gels containing bromelain, used in association with papain, have been demonstrated to be potentially effective in the development of peroxide-free tooth whitening gels [124]. Bromelain, used in association with other active ingredients, has also been observed to increase the function of macular pre-ganglionic elements, as demonstrated in a recent RCT that included thirty patients with intermediate age-related macular degeneration [125]. In a multi-center, open-label, non-comparative clinical trial, 398 women with endometriosis-associated pelvic pain were treated for six months with bromelin, N-acetyl cysteine and alpha lipoic acid. The treatment provided a significant improvement in endometriosis-associated pelvic pain (visual analogue scale >4 diminished from 92.7% to 82.7% (\(p<0.05\))) [126]. Bromelain supplementation in people with inflammatory bowel disease is another potential indicator of its efficacy. Although new RCTs are urgently needed to better understand the effects of bromelain on the prevalence, severity and stemness of colitis, quality of life and markers of inflammation, this supplement decreased the harshness of colonic inflammation. This effect is probably due to its proteolytic action, which most likely eradicates the cell-surface receptors involved in leukocyte defection and activation [127]. Bromelain has also shown relevant activity in allergic airway diseases [128], decreasing the serum levels of interleukins (IL)-4, -12, -13, -17 and interferon-alpha, bronchoalveolar lavage leukocytes (eosinophilis and lymphocytes), cellular infiltrates and bronchoalveolar lavage CD4+, CD8+ T CD4+ and CD25+T cells [129]. However, there is also a lack of RCTs in this case. Topical applications of bromelain have been tested for skin wounds, burns and the debridement of necrotic tissues [130]. Bromelain includes a specific fraction of escharase, which is considered to be the main debriding agent and can selectively act upon damaged tissues without harming healthy ones [2; 131]. The escharase fraction has been demonstrated to accelerate healing and repepithelialization by simplifying the debridement process [132]. In a multi-center, open-label RCT, patients (4-55 years old) with deep partial and full thickness burns, covering 5-30% of their total body surface area, were either treated with a topical application of bromelain (for 4 h) or with the standard of care, which included either surgical excisional or non-surgical debridement. Treatment with bromelain significantly decreased the need for surgery, area of burns excised and the time from injury to complete debridement compared with standard care (_p_ < 0,0001 for all) [133]. The updated guidelines of a multi-professional expert panel of plastic surgeons and burn-care specialists recommended the use of bromelain as an enzymatic debriding agent for burns [134]. In a preliminary study, eight patients with pityriasis lichenoides chronica were treated with bromelain (40 mg three times a day for one month, 40 mg twice a day for one month and 40 mg a day for one month) and showed an improvement in the condition that can probably be traced to its anti-inflammatory, immunomodulatory and/or anti-viral properties [135]. Although bromelain supplementation seems to be effective in many diseases, some limitations should be emphasized. Firstly, the sample populations considered in the studies were small and heterogeneous, the treatment period was limited and the bromelain dosages and types of extracts used were extremely variable, even when administered for the same disease. In addition, only a single clinical trial is available for most of the conditions mentioned in the literature. Finally, few data on bromelain safety are available, especially for long-term treatment.