Abstract
Maca, a plant native to the Peruvian highlands, contains (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA). The family of the tetrahydro-β-carbolines has been associated with both biologically helpful and harmful compounds. We present evidence that MTCA is a natural constituent of Maca, and on consumption no toxicity is found. This suggests that, when consumed as multi-component, MTCA may loose its adversity as drug action.
Keywords: Lepidium meyenii, Maca, methyltetrahydro-β-carbolines, polyphenols
Maca (Lepidium meyenii) is a cruciferous herb, usually found above 3300 m in the Peruvian Andes. It is traditionally used for nutritional and fertility-enhancing properties (1). Among other compounds, hypocotyls of Maca contain (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) in the butanolic fraction (2). This compound, a member of the family tetrahydro-β-carbolines, has been suggested to be an inhibitor of the monoamine oxidase (MAO) enzyme, and that it is co-mutagenic or is a precursor to mutagenic compounds. These mutagens can cause neuronal death in vitro or they can be bioactivated, giving rise to endotoxins. It is also mentioned that tetrahydro-β-carbolines may play an essential role in craving associated with addictions (2).
The mutagenic effect of MTCA on Salmonella typhimurium TA100 in the absence of S9 has been described in Japanese soy sauce treated with exogenous nitrites (7). However, MTCA is not mutagenic on S. typhimurium TA100 in the absence of the nitrites, with or without S9 (3).
These results have motivated the French Agency for Sanitary Security (AFFSA) to issue an alert about health risks associated with the consumption of pulverized Maca (4). The alert describes an alkaloid derived from MTCA that inhibits MAO and can produce neuronal death.
Conflicting observations necessitate research to determine the true actions of MTCA in the human body. MTCA naturally occurs in fruits like oranges, grapefruits, and other fruit juices (5). These are frequently consumed because of their favorable health properties. Recently, MTCA has been described in a fermented garlic extract (6,7). Its concentration increases with time and this in turn increases anti-oxidant activity. Herraiz (personal communication) has detected MTCA in several foods, some showing concentrations greater than that naturally found in Maca.
MTCA accumulates in mammalian tissues and fluids and, in presence of nitrites, is a mutagenic compound precursor (3). Our research demonstrates the absence of mutagenic effects of Maca to the S. typhimurium TA100 in absence or presence of S9 (L. Villegas et al., unpublished observations). Recently, it has been demonstrated that MTCA can inhibit the production of nitrites induced by LPS (7), preventing the conversion of the MTCA to other non-beneficial metabolites.
Manabe et al. (8) suggested that high-MTCA levels correlate with the development of cataracts. However, subsequent studies have demonstrated that MTCA has anti-oxidant capacity greater than that of Vitamin E, and offers significant protect against ultraviolet radiation (9). Recent rat models show an aqueous extract of Maca, obtained after following a traditional boiling process, protected epidermal cells from the damaging effects of ultraviolet radiation (10).
Polyphenols can inhibit MTCA mutagenicity in presence of nitrites (11). Research shows that polyphenols are important constituents of Maca and they can be related to beneficial effects (10).
In relation to the suggestion that MTCA found in Maca can inhibit MAO activity and alter neuronal function (2), our laboratory recently demonstrated that MTCAs do not affect MAO activity in brain (12). This outcome contrasts with the effects of other β-carbolines (13). Research shows MTCA in Maca is not neurotoxic, rather it improves memory and learning in mice (12,14). Having a favorable effect on the experimental mouse model for Alzheimer (12), Maca constitutes a potential treatment for this pathology. Results of recent MTCA–Maca research, taken in conjunction with the fact that Maca contains several beneficial compounds, some of which has anti-carcinogenic properties (1,15), leads us to conclude that Maca consumed as a whole plant must not generate undue health concerns. As mentioned in the French alert (4), our conclusion incorporates the lack of reported toxicity where Maca is consumed after a traditional boiling process.
MTCA is natural constituent of many plants and no toxicity is found on consumption of such whole plants. This suggests that as multi-component, MTCA may loose adverse drug action.
References
- 1.Valerio L, Gonzales GF. Toxicological aspects of South American herbs: Uncaria tomentosa (Cat's Claw) and Lepidium meyenii (Maca). A critical synopsis. Toxicol Rev. 2005;24:11–35. doi: 10.2165/00139709-200524010-00002. [DOI] [PubMed] [Google Scholar]
- 2.Piacente S, Carbone V, Plaza A, Zampelli A, Pizza C. Investigation of the tuber constituents of maca (Lepidium meyenii Walp) J Agric Food Chem. 2002;50:5621–5. doi: 10.1021/jf020280x. [DOI] [PubMed] [Google Scholar]
- 3.Wakabayashi K, Ochiai M, Saito H, Tsuda M, Suwa Y, Nagao M, et al. Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, a precursor of a mutagenic nitroso compound, in soy sauce. Proc Natl Acad Sci USA. 1983;80:2912–6. doi: 10.1073/pnas.80.10.2912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.APSSA. From the French Agency of Sanitary Security on foods relative to the risk assessment for health by consuming pulverized maca roots or as alimentary supplement. Afssa-Saisine 2004-SA-0155. 2004:1–3 [Google Scholar]
- 5.Herraiz T, Galisteo J. Tetrahydro-beta-carboline alkaloids occur in fruits and fruit juices. Activity as antioxidants and radical scavengers. J Agric Food Chem. 2003;51:7156–61. doi: 10.1021/jf030324h. [DOI] [PubMed] [Google Scholar]
- 6.Sato E, Kohno M, Niwano Y. Increased level of tetrahydro-beta-carboline derivatives in short-term fermented garlic. Plant Foods Hum Nutr. 2006;61:175–8. doi: 10.1007/s11130-006-0028-2. [DOI] [PubMed] [Google Scholar]
- 7.Ichikawa M, Yoshida J, Ide N, Sasaoka T, Yamaguchi H, Ono K. Tetrahydro-beta-carboline derivarives in aged garlic extract show antioxidant properties. J Nutr. 2006;136(Suppl 3):726S–31S. doi: 10.1093/jn/136.3.726S. [DOI] [PubMed] [Google Scholar]
- 8.Manabe S, Yuan J, Takahashi T, Urban RC., Jr Age-related accumulation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid in human lens. Exp Eye Res. 1996;63:179–86. doi: 10.1006/exer.1996.0106. [DOI] [PubMed] [Google Scholar]
- 9.Pari K, Sundari CS, Chandani S, Balasubramanian D. β-Carbolines that accumulate in human tissues may serve a protective role against oxidative stress. J Biol Chem. 2000;275:2455–62. doi: 10.1074/jbc.275.4.2455. [DOI] [PubMed] [Google Scholar]
- 10.Gonzales-Castañeda C, Gonzales GF. Hypocotyls of Lepidium meyenii (maca), a plant of the Peruvian highlands, prevents the ultraviolet A, B and C (UVA, UV B and UV C)-induced skin damage in rats. Photodermatol, Photoimmunol Photomed. 2008;24:24–31. doi: 10.1111/j.1600-0781.2008.00330.x. [DOI] [PubMed] [Google Scholar]
- 11.Higashimoto M, Akada Y, Sato M, Kinouchi T, Kuwahara T, Ohnishi Y. Inhibitory effects of tea extracts on the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid on treatment with nitrite in the presence of ethanol. Food Chem Toxicol. 2000;38:7–13. doi: 10.1016/s0278-6915(99)00121-0. [DOI] [PubMed] [Google Scholar]
- 12.Rubio J, Dang H, Gong M, Liu X, Chen S-L, Gonzales GF. Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice. Food Chem Toxicol. 2007;45:882–90. doi: 10.1016/j.fct.2007.04.002. [DOI] [PubMed] [Google Scholar]
- 13.Herraiz T, Chaparro C. Analysis of monoamine oxidase enzymatic activity by reversed-phase high performance liquid chromatography and inhibition by beta-carboline alkaloids occurring in foods and plants. J Chromatogr A. 2006;1120:237–43. doi: 10.1016/j.chroma.2005.12.009. [DOI] [PubMed] [Google Scholar]
- 14.Rubio J, Caldas M, Dávila S, Gasco M, Gonzales GF. Effect of three different cultivars of Lepidium meyenii (Maca) on learning and depression in ovariectomized mice. BMC Complement Alternat Med. 2006;6:23. doi: 10.1186/1472-6882-6-23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Gonzales GF, Valerio LG., Jr Medicinal Plants from Peru: a review of plants as potential agents against cancer. Anti-Cancer Agents Med Chem. 2006;6:429–44. doi: 10.2174/187152006778226486. [DOI] [PubMed] [Google Scholar]
