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Part two: botanical, genetic and chemical studies, and the effect on cells, animals and humans

  • Chapter I: botanical and genetic studies

  • Chapter II: chemical studies of maca

  • Chapter III: study of cells, animal and human

  • Chapter IV: cultivation of maca and physiological studies.

In chapter II of part one, reference is made to properties of maca such as its fertilizing, aphrodisiac (frigidity and impotence), revitalizing and regulating action, as well as the ancestral use of fresh roasted maca roots, referred to as “Huatia” and the preparation of bread, based on cooked dry roots, known as “Atunca.” Mention is also made of its current popular use in various preparations such as juices, strong alcohols, capsules and tablets. Chapter II of part two is devoted to chemical studies of maca and refers, in turn, to the following works:




  • Garró et al (1993), “Extracción, separación e identificación por cromatografía de alcaloides de lepidium meyenii walp (maka)” (Extraction, separation and identification by chromatography of Lepidium meyenii walp (maka) alkaloids). Four fractions of alkaloids were separated from the dry and crushed roots of the plant.




  • Yllescas (1994), Thesis for the title of pharmaceutical chemist entitled “Estudio químico y fitoquímico comparativo de 3 ecotipos de Lepidium meyenii Walp “Maca” procedente de Carhuamayo (Junín)” (Comparative chemical and phytochemical study of three Lepidium meyenii Walp “Maca” ecotypes originating from Carhuamayo (Junín)). Roots of stabilized and crushed maca were used, on which the phytochemical action was carried out to identify three alkaloids and a flavonoid, as well as observing the presence of steroids and triterpenes, phenol compounds, flavonoids and/or cumarins, tannins, glycosides, saponines, free amino acids, secondary aliphatic amines and tertiary amines.




  • Garró, León, Fuertes and Carrasco (1995), “Investigación química y biológica de Lepidium meyenii walp “maca” (Chemical and biological research into Lepidium meyenii walp “maca”, published in the UNMSM review Theorema. Powder of maca roots and a methanol extract of dried and crushed roots were used, as well as fine layer analytical chromatography, finally reported as fruit bearing components and alkaloids.

“Estudio Botánico y químico de los ecotipos amarillo y morado de Lepidium peruvianum “Maca”. Evaluación de su toxicidad aguda” (Botanical and chemical study of the yellow and purple ecotypes of Lepidium peruvianum in “Maca”. Evaluation of its acute toxicity”) (1997), carried out by professionals from UNMSM and the American Phytotherapy Institute, including Dr. César Fuertes. Three alkaloids (in the ether extract), flavonoids, saponines and glycosinolates were reported.


Page 118 contains a general framework for ranges obtained in various analyses of dried “maca” from micronutrients, vitamins, minerals and calories, within which a value of carbohydrates is presented from 51.81 per cent up to 76.05 per cent; for proteins from 10.10 per cent to 18.25 per cent; and fats from 0.20 per cent up to 2.20 per cent.


  1. F. Retuerto et al, (1996), “Efectos citostáticos del extracto etanólico de Lepidium meyenii W. En células meristemáticas de Allium cepa L.” (Cytostatic effects of the ethanol extract of Lepidium meyenii W. In meristematic cells of Allium cepa L). Biological Science Research Institute “Antonio Raymondi” (ICBAR), March 13-15, 1996.

There is a strong belief that the consumption of Lepidium meyenii Walpers (Cruciferae), ie “maca,” has aphrodisiac effects and causes an increase in human fertility. The composition of hydrolyzated carbohydrates is 59 per cent, most of which are thioglucosides. Bulbs of A. Cepa L., with roots of two to three centimeters in length, kept constantly at 20 +/- 0.5oC in aired water and darkness, are submerged in a solution of ethanol extract of L. Meyenii W., of six per cent for 2, 4, 6, 8, 10 and 12 hours respectively, whereby the mytotic index (MI) and the phase index (PI) of the meristematic population being treated are analyzed. Four thousand cells were analyzed.


The MI of the meristematic cells decreased from an MI=13 (control) to an MI of 7.45 after 12 hours’ treatment. The roots treated with the ethanol extract demonstrate a cytostatic effect through the presence of C-mytosis; suggesting the results of the activity of the ethanol extract are due to the thioglycosides present in the extract.


  1. M. E. Valdivia et al (1998) “Efecto de la soya y maca sobre la morfología y fisiología espermática en ratones”(Effect of soya and maca on the sperm morphology and physiology of mice), Seventh Ibero-American Congress of Cellular Biology, October 26-30, 1998.

The weekly in vivo effect of natural products (soya and maca) in male mice is studied, using the alcoholic form of maca. It is concluded that maca may be used to stimulate fertility.




  1. Rodolfo Tello Saavedra and Mary Porras Osorio (1999) “Estudio técnico para la elaboración de licor de maca (Lepidium meyenii Walp) por maceración” (Technical study for the preparation of maca strong alcohol (Lepidium meyenii Walp) by maceration), a research work carried out in the National University of Central Peru, starting in July 1998 and ending in August 1999.

In the summary portion, it is mentioned that a flow of operations was as follows: selection and classification, weighing, washing, REHYDRATION, MACERATION, decanting, filtration, standardization, packaging and storage. It is specified that the soaking and/or rehydration are carried out with hot water at 40oC for a period of 24 hours, thereby eliminating the alkaloids and/or antinutrients which maca possesses. The optimum period for maceration of maca in extra fine alcohol of 96o gl was 13 days, in a proportion from one to three (maca-alcohol).


This document describes a process for preparing a strong alcohol with a rehydration step which amounts to an aqueous extraction, eliminating this aqueous extract and following with the ethanol maceration step, which amounts to a second consecutive extraction process.


  1. L. W. Wattenberg (1987), “Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia A/J mice.” Carcinogenesis 8 (12): 1971-1973. Summary only.

The inhibitive effects of benzyl isothiocyanate on carcinogenesis induced by the chemical carcinogens dimethylnitrosamine and benzopyrene were studied in mice. The results showed that the benzyl isothiocyanate compound, a natural derivative in cruciferous plants, completely inhibits formation of tumors both in the stomach and in the lungs.




  1. K. A. Steinmetz and J. D. Potter (1996), “Vegetables, fruit, and cancer prevention; a review.” J Am Diet Assoc, October 1996 (10): 1027-1039. Summary only.

A revision of various studies relating to the consumption of fruit and vegetables and the risk of cancer was made. From 202 epidemiological studies in humans and 22 studies in animals, it is concluded that there is evidence of a preventive effect of various types of cancer: in the stomach, oesophagus, lungs, oral cavity, pharynx, endometry, pancreas and colon, through the consumption of certain vegetables, including cruciferous plants; among the substances or phytochemical compounds involved in this effect, isothyocyanates are some of the most frequently mentioned.


In the annex to this report reference is made to other texts which represent important precedents for studies carried out in relation to maca.
(iii) Analyses in relation to the international application
Claims referring to extracts (1 to 11)
91 From the revision of the cited documents, known aqueous extracts of Lepidium are considered (references 1, 4 and 5), together with the fact that a polysaccharide or carbohydrate component is a component normally present in the root in percentages which vary from 51.81 per cent to 76.05 per cent; for which reason, the composition defined in claim 1 does not meet the requirement of novelty, thereby also affecting its dependent claims, for example where they specify that additional components are amino acids, which have also been described as usual Lepidium components (reference 5), or in the case of benzyl isothiocyanates (derivative of a thioglycoside), esterols or fatty acids preferably present in extracts using alcohol (references 1, 4, 5 and 6), and it is concluded that claims 1 to 4, 6 and 7 do not meet the requirement of novelty.
92 Although claims 5 and 8 to 11 meet the requirement of novelty in that they refer to the macamide component, however, it is not clear from the description of the application that the macamide component is responsible for the activity.
93 It is noted that biological tests are generally carried out with extracts which comprise multiple components, including components with benzyl isothiocyanate and esterols to which the biological activity of maca is attributed (references 3, 4, 5 and 6). In this sense, it is OBVIOUS that an extract which contains these components with verified activity would maintain the desired activity, since claims 5 and 8 to 11 do not meet the requirement of inventive step, as explained in more detail in point (iv).
Claims referring to macamides (12 to 15)
94 Claim 12 for the compound N-benzyl octanamide, referred to by the applicant as macamide A or MA-3, does not meet the requirement of novelty, since this compound has already been described in the 1996 publication by Adamczyk et al., cited in the analyses of the American Publication US 2002/0042530: in the prior art, the compound is described as part of an example of synthesis of amides and not as an isolated maca component.
95 In the case of claims 13 to 15 which define three amides of fatty acids, it should be observed that although the compounds in question may be novel, as in the prior art only fatty acids and amines are described as a component of maca (reference 5), it is necessary to demonstrate that the compounds are biologically active, for which reason they may meet the requirement of industrial applicability. This information is not clear from the content of the application, since although in table 2 the activity of macamide A (MA-3) is tested, this corresponds to the compound N-benzyl octanamide which does not meet the requirement of novelty, and further information is not provided in relation to the biological activity of the three isolated compounds defined in claims 13 to 15 in comparison with the extracts comprising multiple components.
96 It is understood that a compound with unknown activity does not meet the requirement of industrial applicability, a fact which may apply to claims 13 to 15.
Claims referring to an extraction process (16 to 32)
97 The extraction process defined in claim 16 is anticipated by the extraction processes known as maceration in the case of an alcohol extract or infusion or cooking in the case of an aqueous extract (references 1, 4, 5 and 6), for which reason it does not meet the requirement of novelty, and this also affects its dependent claims, since although in claim 16 an aqueous solvent is mentioned, in the dependent claims it is specified that the solvent is water, alcohol or a mixture of both.
98 On the other hand, it should be pointed out that chromatography techniques are routinely used in processes for separating and identifying components.
Claims referring to therapeutic methods – uses (33 to 54)
99 Claims 33 to 54 as drafted define therapeutic methods which are not patentable, in accordance with a number of different legislative acts, including Decision 486 of the Commission of the Andean Community. In all cases, it should be considered that:
100 Use in the treatment of cancer appears to be anticipated by document 6 which describes the use as cytostatic for the ethanol extract, owing to the presence of thioglycosides: use as an anticarcinogenic agent is known in many members of the Brassicaceae family to which maca belongs.
101 This effect is attributed to the glucosinolate and isothiocyanate components which are found in the Brassicaceae family, mainly to benzyl isothiocyanate, which has been previously isolated and characterized in Lepidium meyenii by Johns (1980). In addition, this effect of the isothiocyanates has been studied in epidemiological terms both in animals and in humans with positive anticarcinogenic effects for different types of cancer (references 9 and 10).
102 The use in the treatment of sexual dysfunction, such as subnormal libido, impotence or subnormal fertility, appears to be anticipated by the traditional use as an aphrodisiac and fertilizing agent (reference 5), complemented by biological tests in animals (references 1, 2 and 3).
103 In conclusion, in light of the above and considering both the documents cited in the International Search Report and those obtained today by the working group: claims 1 to 4; 6; 7; 12; 16 to 32; and 33 to 54 do not meet the requirement of novelty. Although claims 5 and 8 to 11 meet the requirement of novelty, they do no meet the requirement of inventive step.
104 Since the biological activity of the isolated compounds 13 to 15 is not documented, it is possible that they do no meet the requirement of industrial applicability, despite the fact that the compounds in question are novel.
(iv) Analyses in relation to patents of the United States of America
105 Claim 1 of patent no. US 6,297,995 defines an extract which contains four main components, the extract also being defined by its production process.
106 Claim 1 of patent no. US 6,428,824 defines the use of this extract in a method for the treatment of sexual dysfunction.
107 Taking into account the fact that a Lepidium extract has not been described which contains the macamide component (d), nor is a process described with two extraction steps, using firstly 90 per cent water and subsequently 90 per cent alcohol, with a publication date prior to March 3, 1999, both claim 1 of patent no. US 6,297,995 and claim 1 of patent no. US 6,428,824 appear to meet the requirement of novelty, since only aqueous, alcohol or hydroalcohol extracts, or successive extractions, have been described, but with the use of four solvents (references 1, 4, 5 and 7).
108 Since the final composition obtained in claim 1 is a strong alcohol, as this relates to an alcohol extract, it is considered that the closest prior art is reference 4 which also describes an ethanol extract of maca and its production process, using alcohol rectified in a laboratory or a domestic maceration using strong alcohol, rum or cane alcohol, an extraction which contains between 20 and 40 g of the maca root per liter of alcohol.
109 In accordance with examples 2 and 3 of the patent description, it is clear that in:

  • example 2 of the American patent 500 mg of maca root is used together with 14 liters of water, thereby obtaining an extract which evaporates completely until 20 g of a product is obtained, containing 0.01 per cent of esterols, 0.1 per cent of fatty acids, nine per cent of amino acids and 44 per cent of polysaccharides;

  • example 3, the residue of example 2 is used, which is extracted with 15 liters of 100 per cent SDA alcohol, i.e. 33.3 g per liter of alcohol, thereby obtaining an extract which evaporates completely until 10 g of a product is obtained, containing 7.8 per cent benzyl isothiocyanate, 1.8 per cent esterols, 22 per cent fatty acids and 12 per cent macamide component.

110 Although reference 4 describes a single-step process using ethanol, the fact that it mentions that in this extraction process components such as proteins and carbohydrates would be lost, owing to the fact that they are not soluble in ethanol, this may suggest the need to find a process in which these components are not lost, which actually occurs in the claimed process that, by means of the first aqueous extraction, allows nine per cent of amino acid component and 44 per cent of polysaccharide component to be recovered, and it is therefore OBVIOUS in relation to reference 4, since the selection of water as a solvent in accordance with the solubility known for these components is predictable.


111 In relation to the components of the extract, the fact that the first three components are known as components of maca and are attributed mainly to the benzyl isothiocyanate components and esterols with biological activity, appear to make it necessary to demonstrate the advantages of an extract with macamide component over another extract which does not contain that component, for which reason the comparison made in examples 9 to 11 for examples 1 and 5 provides insufficient evidence, and since it deals with component mixtures of different concentrations does not allow a correct comparison to be made. Thus, although in example 5, 4.4 per cent of macamide is detected, a larger quantity of benzyl isothiocyanate (4.1 per cent) and esterols (0.4 per cent) than that detected in example 1 (0.89 and 0.079 per cent) is also observed, as may be noted in the following table:


Component

Example 1

Example 5

Benzyl isothiocyanate

0.89%

4.1%

Lepidium esterols

0.079%

0.4%

Lepidium fatty acids

1.46%

12%

Macamide components




4.4%

Amino acids

8.72%




Polysaccharide

41.9%




Total of solids

77%



112 Since there is no proof to demonstrate the unexpected advantages of the claimed extract, in that it has ten per cent or more of macamides, this does not meet the requirement of inventive step.


113 Patent no. US 6,428,824 is a fractional application of patent no. US 6,267,995, and in claim 1 therein reference is made to the use of the extract defined by four components for the treatment of sexual dysfunction.
114 In the article by Johns, cited in the International Search Report, and in reference 3, details are given of the benzyl isothiocyanate component, derived from a glycoside, and of the esterols with biological activity. Reference 4 describes how the alkaloids and a number of glycosides will be found in an ethanol extract. In reference 7, it is noted that an ethanol extract of maca may favor fertility. Taking into account that the revised report does not provide a better demonstration of the beneficial effect of the macamide component, it may be concluded, in accordance with the description given by Johns and references 3 to 7, that it is OBVIOUS that an alcohol extract, in containing benzyl isothiocyanate and esterols among its components, will maintain the traditional use attributed to maca as an aphrodisiac and a fertilizing agent.
115 On the other hand, it should be highlighted that many references exist by various authors who, working both with maca extracts and the cooked and liquefied plant, have tested this beneficial effect on animals, as may be noted in reference 1 where an alkaloid extract is tested in rats and toads: reference 2 in lambs, reference 3 in rats and reference 7 in mice; the conclusion of all such authors is that maca possesses a beneficial effect on fertility.
116 In conclusion, the claims included in patents nos. US 6,267,995 and US 6,428,824 are suggested by the new prior art compiled by the working group, thereby affecting its inventive step.

IX. IN ADDITION TO PATENTS


(i) Access to genetic resources
117 The patents referring to Lepidium meyenii also bring to light problems connected with the method of access to these materials and whether compliance has been achieved with the basic principles of the CBD and with the relevant legislation in force in the Andean region and Peru (specifically with Decision 391 concerning a Common Regime on Access to Genetic Resources). Attention is drawn to the fact and concern expressed that the intellectual property regime (in this specific case that relating to patents) grants rights over materials and resources which could have been obtained unlawfully, contrary to the specific Decision 391 or even the rules in force for collecting and exporting biological materials.
(ii) Protection of knowledge
118 Lepidium meyenii has been known and used in various ways and for different purposes by indigenous populations in Peru since time immemorial. One question which arises as a result of the patents analyzed is the degree of indigenous knowledge which was used to generate the claimed inventions. In addition to whether or not rules exist for regulating or protecting indigenous knowledge, or whether it is possible to do so once this knowledge is disseminated outside the sphere of the communities in question, it is obvious that at any point in time during the scientific process of research and development (recent or past), which gave rise to these inventions, this knowledge must have been used directly or indirectly.

X. CONCLUSIONS AND FINAL REMARKS


(i) As regards the international patent application, some of the analyzed claims do not meet the requirement of novelty; although certain others do, they do not meet the requirement of inventive step; finally, since the biological activity of the isolated compounds of claims 13 to 15 has not been demonstrated, these claims do not appear to meet the requirement of industrial applicability. In sum, the claimed invention does not appear to be patentable in these terms.
On the other hand, as regards the inventions claimed in American patents, from the analysis made it is concluded that they do not meet the requirement of inventive step. In this regard, these patents are very questionable from a legal point of view.
(ii) Six of the seven inventors mentioned in the patents of the United States of America and international applications analyzed recognize that they obtained dry maca roots from Peru in 19982. However, there is no evidence that: (i) these materials have been lawfully obtained from Peru or that they comply with the corresponding national legislation, and (ii) that provision has been made for the equitable sharing with the country of the benefits derived from the use of these patents.
(iii) A third conclusion which emerges from the work of this group is the enormous difficulty encountered by the country in its attempts to challenge or question, for administrative or legal reasons, in the United States or Europe, patents of this nature. Although the rules of the game are clear, the reality is that even where we wish to use them, the costs, time, and need for specialized advice make effective action in relation thereto and other similar patents very difficult. Any action taken after the event is prohibitively expensive.
(iv) The methodology used by the Working Group, combining local and international experience, complementing the scientific and legal capabilities, and acting in an open and participation-based manner, make it possible to conclude that as an area for evaluating and analyzing similar patents, this form of work is appropriate and it is to be hoped that the possibility arises to institutionalize the functioning and operation of a national group or committee which is directly responsible for cases such as that analyzed.
(v) This national group or committee should assess a monitoring or early-warning mechanism, providing familiarity with similar situations where, through the use of materials or components of national biological diversity (without following the corresponding procedures) or ancestral knowledge of our communities (without their consent), or through a mistaken interpretation of the specific rules or principles of intellectual property, attempts are made to invoke particular rights. In addition, the group must establish a channel of communication with patent and intellectual property offices in other countries so that they request information from it when applications on resources or materials of Peruvian origin are filed.
(vi) It has remained clear that, although much literature and information exists (a great deal of which is clearly documented and is in the public domain) on Lepidium meyenii, access to this information (and its general availability) is at times difficult. This explains why patent offices from third countries have not institutionalized the practice of revising documents and literature which could refer to ancestral uses of components of biological diversity by indigenous peoples or to different manifestations of traditional indigenous knowledge. These practical difficulties affect the possibilities for rigorous and comprehensive examinations of patent applications, giving rise, in many cases, to the granting of rights of doubtful legitimacy.
(vii) The latter gives rise to the need to evaluate how it would be possible to organize and systematize much of this information and the role that could be played by a national database in that regard. In summary, how is it possible to articulate this database and information with the search procedures and examinations of the main patent offices throughout the world in order to avoid patents being granted on the basis of partial and limited examinations of novelty and inventive step.
(viii) Such principles and rules contained in the Andean Community Legislation (Decision 486 on the Common Industrial Property Regime), Costa Rica, Brazil and some other countries, in which supervision of the origin of biological materials and knowledge which could be part of an invention (especially in the biotechnology field) is required, and where it is even necessary to demonstrate the legal provenance of these materials as a requirement for the processing of patent applications, should be incorporated in international patent legislation and the domestic legislation of all countries. This is an alternative for avoiding cases of biopiracy in which attempts are made to invoke rights over products which incorporate materials unlegally or unlawfully obtained and used.
(ix) As the country of origin of a great variety of native crops with commercial and industrial potential, it is to be hoped that in the future in Peru cases similar to that of Lepidium meyenii continue to be presented. In that regard, there is an urgent need for the development of a standard for protection of native crops.
(x) As the country of origin, Peru should consider the possibility of participating much more actively in the research and development processes relating to plants and biological materials and, especially, being party to the benefits derived from the products resulting from such research and development. For that purpose, a national legal regime is required to generate appropriate incentives for cooperation in research and development.
(xi) As a final comment, it will be very difficult to generate appropriate incentives for the preservation of biological diversity and compliance with the CBD in general, not only where cases such as the subject of analyses in this report are presented but, for example, situations such as those imposed by the European regulations on Novel Foods arise (European Communities Regulation (EC) 258/97 of January 27, 1997) which have already led to restrictions on the export of maca from Peru to Europe.
These initiatives place at risk any possibility of exporting products prepared from the biodiversity existing in Peru, since as they are considered to be novel foodstuffs or medicinal plants, it should be verified that their use is not harmful to human beings, which would be very costly and complicated for our country. This specific point does not deal in a precise manner with the subject of patents, but there is a cumulative effect in the sense of biopiracy on the one hand, and trade restrictions on the other. In essence, it places at risk sustainable business which seeks precisely to give value to biodiversity and thereby provide an incentive for its preservation and better use. In the final analysis, it places at risk the political and regulatory agreements assumed as a party to the CBD, insofar as, in practice, the options of countries such as Peru are limited and it simply becomes impossible for the country to meet its obligations.
Lima, May 8, 2003.

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    J Am Diet Assoc, Oct 96 (10): 1027-1039. Summary only.




  1. Tello, R. y Porras, M. 1999. Estudio técnico para la elaboración de licor de maca (Lepidium meyenii walp) por maceración. Trabajo de investigación. Universidad Nacional del Centro del Perú. Instituto de Investigación de la Facultad de Ingeniería en industrias alimentarias. Huancayo, Perú.




  1. Toledo J., P. Dehal, F. Jarrín, M. Hermann, I. Al-Shehbaz and C.F. Quiros. 1998. Genetic variability of Lepidium meyenii and other Andean Lepidium species (Brassicaceae) assessed by molecular markers. Annals of Botany 82: 523-530.




  1. Valdivia, M.E., Del Valle, J.M., Ruiz, M.A., Maima, N.V. y Poma, J.G. 1998. Efecto de la soya y maca sobre la morfología y fisiología espermática en ratones. En: VII Congreso Iberoamericano de Biología celular, Sociedad Ibero-americana de Biología celular, 26-30 de octubre de 1998. Montevideo, Uruguay.




  1. Verhoeven, D., R. Goldbohm, G. van Poppel, H. Verhagen y P. van den Brandt. 1996. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiology Biomarkers and Prevention. Vol. 5, Issue 9:733-748.




  1. Wattenberg, L.W. 1977. Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds. J. Natl. Cancer Inst., February 1, 1977; 58(2):395-398. Summary only.




  1. Wattenberg, L.W. 1983. Inhibition of neoplasia by minor dietary constituents. Cancer Research 43(5):2448s-2453s. Summary only.




  1. Wattenberg, LW. 1987. Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia A/J mice. Carcinogenesis 8 (12): 1971-1973. Summary only.




  1. Wattenberg, L.W. 1990. Inhibition of carcinogenesis by minor anutrient constituents of the diet. Proc. Nutr. Soc. July 1, 1990; 49(2):173-183.




  1. Zolezzi, O. 1997. Transformación de la uña de gato y la maca en el Perú. En: Tercer Encuentro de la Agroindustria Rural. Tarapoto, Perú. pp 31-38.




  1. Zúñiga, E. 1992. El cultivo de la maca (Lepidium meyenii, Walp.). Agronomía, XL (2): 54-56.



List of additional references relevant tomaca


  1. Aguila Calderón, J. y Chacón de Popovici, G. 1998. El valor nutricional de la “maca” (Lepidium peruvianum Chacón) en niños anémicos por desnutrición. Trabajo presentado al II Curso nacional de maca. Huancayo, del 3 al 5 de diciembre de 1998.




  1. Aliaga, R. 1999. Guía para el cultivo, aprovechamiento y conservación de la maca Lepidium meyenii Walpers. Convenio Andrés Bello. Santa Fe, Colombia. 50 pp.




  1. Arroyo Acevedo, J. y Sandoval de Arroyo, S. 1997. Inocuidad de la maca (Lepidium peruvianum Chacón) con respecto a la DL50. Sección Farmacología de la Facultad de Medicina Humana de la Universidad Nacional Mayor de San Marcos.




  1. Bauer, R., Remiger, P. and Wagner, H. 1988. Alkamides from the roots of Echinacea purpurea. Phytochemistry, 27(7): 2339-2342. Summary only.




  1. Bauer, R., Remiger, P. and Wagner, H. 1989. Alkamides from the roots of Echinacea angustifolia. Phytochemistry 28(2): 505-508. Summary only.




  1. Cabieses, F. 1997. La maca y la puna. Universidad San Martín de Porres. Primera edición. Lima, Perú. pp. 65-94.




  1. Capcha, R., Rojas, P., Aguilar, J. 2000. Toxicidad Aguda (DL50) para dos extractos estandarizados de Uncaria tomentosa (Willd.) DC. y un extracto de Lepidium meyenii (maca) rico en glucosinatos. Summary book of First International Congress FITO 2001. Lima, Perú. Pp. 159-160.




  1. Castro de León, M. 1990. An Andean crop in extinction: Case of maca. Perú Indig. 12(28): 85-94.




  1. Chacón de Popovici, G. 1990. La maca (Lepidium peruvianum Chacón sp.nov.) y su habitat. Revista Peruana de Biología 3(2) : 171-267.




  1. Chacón de Popovici, G. 1997. La importancia de Lepidium peruvianum Chacón (Maca) en la alimentación y salud del ser humano y animal, 2000 años antes y después de Cristo y en el siglo XXI. Servicios Gráficos Romero. Lima, Perú. 137 pp.




  1. Chacón de Popovici, G. 1998. Análisis cuali-cuantitativo de los 31 elementos de la “Maca” (Lepidium peruvianum Chacón) y otros alimentos nativos del Perú. Trabajo presentado al II Curso nacional de maca. Huancayo, del 3 al 5 de diciembre de 1998.




  1. Chacón de Popovici, G. 1999a. Estudio ecológico, fitoquímico y farmacológico de Lepidium peruvianum Chacon (“maca”). In Maca: Memories of First Course on Maca. ECO. Lima, Perú. pp. 23-42.




  1. Chacón de Popovici, G. 1999b. La maca: Alimentación y salud. INDOAGRO, FONDE. Agronegocios No. 4. Lima, Perú. pp. 50-60.




  1. Cicero, A., Bandieri, E., Arletti, R. 2001. Lepidium meyenii Walp. improves sexual behaviour in male rats independently from its action on spontaneous locomotor activity. Journal of Ethnopharmacology 75 (2001): 225-229.




  1. Cicero, A., Piacente, S., Plaza, A., Sala, E., Arletti, R., Pizza, C. 2002. Hexanic Maca extract improves rat sexual performance more effectively than methanolic and chloroformic Maca extracts. Andrologia 34: 177-179.




  1. Cole, R. 1976. Isothiocyanates, nitriles and thiocyanates as products of autolysis of glucosinolates in Cruciferae. Phytochemistry 15(5): 759-762.




  1. Cóndor, D. 1994. Efecto de diferentes niveles de maca en raciones de crecimiento para cuyes. [Effect of different maca (Lepidium meyenii WALP) levels on growth rations for guinea pigs]. In: Summary Book of research on guinea pigs. INIA. pp. 146.




  1. Cuentas Jara, M.J., Domínguez Calderón, J.L., Mendoza Cabanillas, M.C., Mendoza Chávez, H., Montoya Henriquez, J.G., Mori Quispe, N. y Pérez Díaz, D.S. 2000. Efectos del extracto alcaloideo de maca (Lepidium peruvianum G. Chacón) en la función testicular normal y la alterada por administración de decanoato y de nandrolona. Trabajo de investigación. Universidad Nacional Mayor de San Marcos, Sección de Farmacología de la Facultad de Medicina Humana.




  1. Dini A., Migliouolo G., Rastrelli L., Saturnino P. and Schettino O. 1994. Chemical composition of Lepidium meyenii. Food Chemistry 49: 347-349.




  1. Ganzera, M., Zhao, J., Muhammad, I., and Khan, I. 2002. Chemical profiling and standardization of Lepidium meyenii (Maca) by Reversed Phase High Performance Liquid Chromatography. Chem. Pharm. Bull. 50(7): 988-991
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