Human Metabolism and Excretion of Kawakawa (Piper excelsum) Leaf Chemicals.

SCOPE: Piper excelsum (kawakawa) has a history of therapeutic use by Maori in Aotearoa New Zealand. It is currently widely consumed as a beverage and included as an ingredient in "functional" food product. Leaves contain compounds that are also found in a wide range of other spices, foods, and medicinal plants. This study investigates the human metabolism and excretion of kawakawa leaf chemicals. METHODS AND RESULTS: Six healthy male volunteers in one study (Bioavailability of Kawakawa Tea metabolites in human volunteers [BOKA-T]) and 30 volunteers (15 male and 15 female) in a second study (Impact of acute Kawakawa Tea ingestion on postprandial glucose metabolism in healthy human volunteers [TOAST]) consume a hot water infusion of dried kawakawa leaves (kawakawa tea [KT]). Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analyses of urine samples from BOKA-T identified 26 urinary metabolites that are significantly associated with KT consumption, confirmed by the analysis of samples from the independent TOAST study. Seven of the 26 metabolites are also detected in plasma. Thirteen of the 26 urinary compounds are provisionally identified as metabolites of specific compounds in KT, eight metabolites are identified as being derived from specific compounds in KT but without resolution of chemical structure, and five are of unknown origin. CONCLUSIONS: Several kawakawa compounds that are also widely found in other plants are bioavailable and are modified by phase 1 and 2 metabolism.

Acute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population.

Background: Piper excelsum (kawakawa) is an endemic shrub of Aotearoa, New Zealand, of cultural and medicinal importance to Maori. Its fruits and leaves are often consumed. These tissues contain several compounds that have been shown to be biologically active and which may underpin its putative health-promoting effects. The current study investigates whether kawakawa tea can modulate postprandial glucose metabolism. Methods: We report a pilot three-arm randomized crossover study to assess the bioavailability of kawakawa tea (BOKA-T) in six male participants with each arm having an acute intervention of kawakawa tea (4 g/250 mL water; 1 g/250 mL water; water) and a follow-up two-arm randomized crossover study to assess the impact of acute kawakawa tea ingestion on postprandial glucose metabolism in healthy human volunteers (TOAST) (4 g/250 mL water; and water; n = 30 (15 male and 15 female)). Participants consumed 250 mL of kawakawa tea or water control within each study prior to consuming a high-glycemic breakfast. Pre- and postprandial plasma glucose and insulin concentrations were measured, and the Matsuda index was calculated to measure insulin sensitivity. Results: In the BOKA-T study, lower plasma glucose (p < 0.01) and insulin (p < 0.01) concentrations at 60 min were observed after consumption of a high-dose kawakawa tea in comparison to low-dose or water. In the TOAST study, only plasma insulin (p = 0.01) was lower at 60 min in the high-dose kawakawa group compared to the control group. Both studies showed a trend towards higher insulin sensitivity in the high-dose kawakawa group compared to water only. Conclusions: Consuming kawakawa tea may modulate postprandial glucose metabolism. Further investigations with a longer-term intervention study are warranted.

The Potential of Anti-Diabetic Rakau Rongoa (Maori Herbal Medicine) to Treat Type 2 Diabetes Mellitus (T2DM) Mate Huka: A Review.

T2DM (type 2 diabetes mellitus, or Maori term "mate huka") is a major long-term health issue in New Zealand particularly among the Maori community. Non-insulin drugs commonly used in New Zealand for the treatment of T2DM have limits to their efficacy as well as side effects, which are of concern for diabetics. As such, the potential for natural products such as traditional rakau rongoa are of interest for potentially preventing the development of T2DM or improving the treatment of the disease. In particular, anti-diabetic effects have been reported for rakau rongoa such as karamu, kumarahou, and kawakawa. Natural products have been identified in karamu, kumarahou, and kawakawa that have documented potential effects on glucose metabolism that could contribute to the anti-diabetic effect of these rakau rongoa. As such, this could provide scientific insight into the matauranga (traditional knowledge) developed over generations by Maori. However, detailed laboratory based and clinical studies would be required to understand and validate these properties of karamu, kumarahou, and kawakawa, and to understand how they can be used in T2DM treatment. Social determinants of indigenous health such as language, culture, traditional knowledge, and identity, are important in understanding the relationship Maori have with their land and the matauranga they developed of the medicinal properties within their rakau rongoa, over many centuries. Interestingly, traditional Maori views towards scientific research using animal models to test rakau rongoa are varied but supportive. Furthermore, cultural issues surrounding Maori mana motuhake (self-determination) of traditional rongoa Maori healing practices and the inequity faced by many kairongoa (rongoa Maori practitioners) and tohunga (healers) compared to mainstream health are a current issue within the New Zealand health system. As such, a cultural holistic approach for T2DM care among Maori would be advantageous. This review will outline the available evidence supporting the anti-diabetic efficacy of karamu, kumarahou, and kawakawa. Currently though there is a lack of molecular research to understand the mechanisms of this efficacy, as such this review will also outline Te Reo Tipu Research, a kaupapa Maori framework for molecular and genomic research on taonga flora.

Composition and safety evaluation of tea from New Zealand kawakawa (Piper excelsum).

Kawakawa (Piper excelsum) has food, medicinal and cultural importance to the indigenous Maori people of New Zealand, and is being incorporated into a range of commercial food and therapeutic products, including tea. In this study, the chemical compositions of kawakawa fresh leaves, dried leaves for tea, and hot brewed tea, were analysed and compared. The key metabolites were diayangambin, elemicin, myristicin, unidentified lignans and amides. The safety of brewed tea and tea leaves were evaluated in 8 week old Sprague Dawley rats in a 14 day acute study followed by a 28 day subacute study. In the 14 day study, the rats received the equivalent of 1, 2, 3 or 4 cups of kawakawa tea, and the rats in the 28 day study received daily doses that were equivalent to 4 cups per day. There were no adverse effects observed in the rats, and body weights and food intakes were not significantly different between the control and the kawakawa treated animals. There were small differences in organ weights, biochemical and haematology parameters observed in the rats given the kawakawa tea. In conclusion, the consumption of kawakawa tea could be considered safe within the conditions used in this study.