DTU

Note

To: Food Supplement Group, Danish Veterinary and Food Administration

Concerning: Risk assessment of Lepidium meyenii root and hypocotyl

From: The Danish National Food Institute (DTU FOOD),

Technical University of Denmark 23 October 2020
DTU DOCX No 20/1002812

Background
The Food Supplement Group has asked The Danish National Food Institute (DTU FOOD), Technical
University of Denmark, for an updated risk assessment of root and hypocotyl from Lepidium meyenii
Walp. (synonymous L. peruvianum Chacon). The plant has no Danish name, but is sold under the name
‘maca’, which is also used in Spanish and English.

Conclusion
Chemical substances

A large number of qualitative analyses of constituents in the root and hypocotyl of L. meyenii have been
performed, but quantitative data are only available for some substances. No toxicological data are
available to link specific substances or groups of substances to the effects reported in experimental
animals.

Animal studies - general toxicity

The effects of a preparation of the root tested in rats in both a 28- and 90-day study showed that L.
meyenii affected normal growth in male rats resulting in significantly lower body weights in the dosed
groups compared to the control group. In the study, two dose groups were used and an effect was
observed at the lowest dose. Such a lack of normal weight gain is considered an adverse effect.

Animal studies - effects on the reproductive system

Experimental studies of possible effects on reproductive parameters in male animals of various

CVR number DK

preparations of L. meyenii from hypocotyls, tubers or roots as well as commercial products have been
performed.

Technical University of Denmark Kemitorvet Building 202 Tel. +45 35 88 70 00 www.food.dtu.dk

The National Food Institute 2800 Kgs. Lyngby
DTU

Several of the studies show that the roots, tubers or hypocotyles of maca may affect reproductive organs
and accessory reproductive organs, spermatogenesis and/or the sperm count in male rats. The effects
point to an androgenic effect i.e. a change towards masculinisation. DTU FOOD considers the changes as
adverse effects.

A number of studies have been performed on possible effects on reproductive organs and sex hormones
in female mice and rats after dosing with various preparations of the roots, tubers or hypocotyls of L.
meyenii. In addition, experiments have been performed in female ovariectomized mice and rats no
longer having oestrous cycles. Several of these studies have after maca dosing observed changes in
levels of sex hormones: estradiol, the follicle stimulating hormone (FSH), the luteinising hormone (LH),
progesterone (PG) and testosterone, as well as in some cases increased weights of the uterus in
ovariectomized mice, as sign of changes in hormone levels. Overall, animal studies indicate that dosing
with the root and preparations hereof may affect the normal level of sex hormones in females. DTU
FOOD consider such changes as adverse effects.

Human studies

There are several human studies aiming at investigating the effects of maca on sex hormones. Four of
these studies in peri- and postmenopausal women are comparable using similar preparations and doses
of maca and similar study design. For estradiol there is an increase in all three studies. The results for
most of the other measured sex hormones (FSH, LH and PG) are not pointing in the same direction, i.e.
both increase, reduction and no effect after maca intake are observed. Based on the reported human
studies, DTU FOOD considers that it cannot be excluded that 2 g maca per day taken as a food
supplement may affect hormone levels in peri- and postmenopausal women.

Overall conclusion

On the basis of animal studies showing that the roots or hypocotyls of L. meyenii and preparations
hereof can cause both general toxicity and adverse effects on the reproductive system in both males
and females, DTU FOOD considers that it is not possible to establish a dose under which the intake will
be without adverse effects.

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Literature search
To identify relevant articles for the risk assessment of L. meyenii, we searched in the two scientific
databases PubMed and Web of Science. The results are shown in Table 1. The searches were carried out
on 18/2 2020 without limitations.

Table 1. The result of the literature search in PubMed (PM) and Web of Science (WoS) for relevant articles
for the risk assessment of maca.

Database Search # Search terms Number of articles

WOS 1 (maca OR meyenii OR peruvianum) 1703

WOS 2 (peruvian AND ginseng) 2

WOS 3 #1 OR #2 1703

PM 4 ((maca) OR (peruvianum)) OR (meyenii) 913

PM 5 (peruvian) AND (ginseng) 1

PM 6 #4 OR #5 913

Search #3 and #6 were imported to EndNoteTM, where duplicates were removed. The final number of-
papers (n=2127) was transferred to MS Excel for the first review of relevance by screening title and
abstract. Potentially relevant articles were divided into five study types: constituents (n=131),
genotypes/chemotypes (n=21), in vitro studies (n=38), animal studies (n=110) and human studies (n=85).
The second review (consultation of the whole article) resulted in 28 relevant articles for constituents, 8
for genotypes/chemotypes, x for in vitro studies, 29 for animal studies and 14 for human studies. These
articles are used in the risk assessment of maca.

Taxonomy, natural occurrence and chemotypes

L. meyenii (maca) is a domesticated plant that grows at altitudes above 3500 m in the Andes and has a
very high freezing tolerance. L. meyenii is an octaploid plant with 64 chromosomes. Maca was probably
domesticated over 2000 years ago, but it is unclear what the wild origin of the plant is (Toledo et al.,
1998). Among locals, maca is used both in cooking and as herbal medicine. Peru is the leading
production country, but the production has spread to other countries especially China (Wang & Zhu,
2019). The plant has a large spherical or oval root that can be up to 20 cm in diameter, while the green
parts of the plant only reaches up to 10-20 cm. For food supplements, both the hypocotyl and the
conneced primary taproot are used. The tuber (hypocotyl + taproot) is often referred to as “hypocotyl”
(Wang & Zhu, 2019). In the review of the specific articles, the authors’ description of the part of the
plant is used.

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However, it should be stressed that when a writer mentions the use of hypocotyl, it can in fact be both
hypocotyl and taproot that are used in the study. The plant has a large morphological variety, and the
root can have different colours from white, cream-coloured, yellow, orange, red, dark red, violet to
black. Up to 13 colour variants are described. Different phenotypes of L. meyenii are typically referred to
as yellow, red, violet and black maca, which are the more common types (Carvalho & Ribeiro, 2019;
Meissner et al., 2015; Meissner et al., 2016; Wang & Zhu, 2019).

Constituents in root/hypocotyle
There has been a relatively high interest in mapping L. meyenii’s potentially bioactive substances. In a
recent review, Carvalho & Ribeiro (2019) lists 101 different substances, mostly identified in the root
and/or hypocotyl of the plant. This section describes the different substance groups.

Nutrients

The fresh root contains more than 80 % water, but typically the root is dried before further use (Wang &
Zhu, 2019). The water content in the root after traditional air-drying has been measured to about 10 %
by Dini et al. (1994) and Meissner et al. (2016), while Esparza et al. (2015) reported that the average
water content in the dried tubers are 13 %. The nutrient content is influenced by the phenotype, soil
conditions, climate and cultivation method, so there can be a significant variation. The majority of the
dried root consists of carbohydrates (46-74 % of the dry weight), the majority of which is starch.
The content of dietary fibres can vary between 16 to 26 % of the dry weight. The protein content can
vary from just below 10 % to just over 20 % of the dry weight. The fat content is low, typically 0.6 %-
2.2 % of dry weight (Wang & Zhu, 2019).

Glucosinolates

Glucosinolates are a group of thioglucosides that plants use as defensive substances. They are -
widespread in the Brassicaceae, to which L. meyenii belongs, and the substances are found in several
commonly used food plants such as cabbage, mustard and horseradish. Altogether nine different
glucosinolates have been identified in L. meyenii. Benzyl glucosinolate (glucotropaeolin) is the
glucosinolate typically found in the highest concentrations and may account for up to 80 % of the total
glucosinolate content. However, there may be significant qualitative as well as quantitative differences
in the glucosinolate contents between phenotypes or influenced by different cultivation conditions
(Carvalho & Ribeiro, 2019; Meissner et al., 2019; Yabar et al., 2011). Li et. al. (2001) measured the total
glucosinolate content in a variety of maca products. In a sample of fresh root, a total glucosinolate
content of 25.7 µmol/g (content per g dry weight will be 5-10 times higher) was found, while the
content was much lower in a sample of dried root (4.5 µmol/g), and a flour sample containing 4.1
µmol/g (maca flour is produced from the ground dried root). Unlike macamides, the contents of
glucosinolates are highest in the fresh hypocotyl, while the content decreases during drying. Zhang et al.
(2020) found that the total content of p-hydroxybenzylglucosinolate, benzyl glucosinolate and
m-methoxybenzyl glucosinolate decreased from 33.3 mg/g dry weight (approximately
81 µmol/g) to 22.2 mg/g dry weight (approximately 54 µmol/g).

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Macaenes, macamides and other substances related to fatty acids.

Analyses of the fatty acid composition in root/hypocotyl have been performed. In addition to the fatty
acids commonly occurring in plants, the fatty acid 2-oxononadecanonic acid and the fatty acid amides,
anandamide and oleamide, have been found (Qiu et al., 2016; Valentova et al., 2006). In addition, three
macaenes (fatty acid with an oxo-group) have been found: 9-oxo-10E,12E-octadecadienic acid, 5-oxo-
6E,8E-octadecadienic acid and 9-oxo-10E,12Z-octadecadienic acid (Ganzera et al., 2002; Muhammad et
al., 2002; XIa et al., 2018).

A group of substances that has attracted attention is the contents of macamides (N-alkyl-amides), which
is highlighted as a group of substances that has bioactive properties and that may be responsible for the
effects attributed to L. meyenii. Macamides may possibly be formed by a reaction between benzylamine
and fatty acids. Benzylamine can be formed from benzylisothiocyanate, a degradation product of
glucosinolates (Xia et al., 2019) and thus the glucosinolates and macamides content may be connected
to each other. Macamides are fatty acid amides, N-bound to a benzyl group, e.g. N-benzyl-octanamide.
There may be differences in the chemical structure of the substances both in the fatty acid part and in
the benzyl group. Currently, 23 different macamides have been identified (Carvalho & Ribeiro, 2019).
McCollom et al. (2005) found that the total content of 11 analysed macamides in four samples of dried
hypocotyls ranged from 0.0016 % to 0.0123 % (0.016-0.123 mg/g). Both Pan et al. (2016a) and Chen et
al. (2017) found that the place of cultivation was more important for the contents of macamides than
the colour variety. Chen et al. (2017) found that the macamide content (ten quantified macamides) in
the hypocotyls of samples from twenty oven-dried maca from different sites in Tibet varied greatly from
0.07 mg/g dry weight to 4.0 mg/g dry weight (yellow, black and purple colour variations).
Melnikovova et al. (2012) found that L. meyenii grown in the Czech Republic in low-lying areas (257 m
above sea level) did not contain macamides, while the total content of seven macamides in hypocotyls
from three different Peruvian products was 3.1 to 6.2 mg/g dry weight. Pan et al. (2016b) found that the
contents of seven analysed macamides in samples of hypocotyl dried in different ways ranged from
0.58 mg/g to 2.52 mg/g depending on the drying method. Zhang et al. (2020) and Esparza et al. (2015)
found that the drying method is of great importance for the contents of macamides in the hypocotyls.
Drying experiments carried out by Zhang et al. (2020) with maca (black) showed that natural air drying
over 6 months resulted in a higher concentration than the much faster oven drying (after 2 months). The
content gradually increased through the drying period, and in the final product, the total content was
3.5 mg/g dry weight, a 10 times increase in content compared to the content of the fresh hypocotyls.
Esparza et al. (2015) found only a minimum content of 0.012 mg/g dry weight in fresh freeze-dried
Peruvian hypocotyls, while the average content was 0.63 mg/g dry weight in the dried hypocotyls
(average of seven experiments analysing three macamides).

Alkaloids
Many alkaloids have potent bioactive properties. Alkaloids are chemically different, naturally occurring
organic substances containing nitrogen, and thus their bioactive properties may vary considerably. Four
imidazole alkaloids, called lepidiline A-D, have been found in the roots (Cui et al., 2003; Jin et al., 2016).
In addition, three pyrrol alkaloids, called macapyrroline A-C, have been found in the roots (Zhou et al.,
2018), as well as the substances 3-benzyl-1,2-dihydro-N-hydroxypyridine-4-carbaldehyde and (1R,3S)-1-
methyltetrahydro-β-carboline-3-carboxylic acid (Muhammad et al., 2002; Piacente et al.,

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2002).

Hydantoins and thiohydantoins

A long series of hydantoins and thiohydantoins have been identified in L. meyenii. These are the
hydantoins: meyeniihydantoin A-C and macahydantoin C-D, and the thiohydantoins: macahydantoin A-
B, macathiohydantoin B-K (Geng et al., 2018; Tian et al., 2018; Yu et al., 2017a; Yu et al., 2017b, 2018).
Quantitative data on the contents of these substances in L. meyenii are not available.

Phytosterols

Phytosterols are commonly found in the cell membranes of plants. In the hypocotyls of L. meyenii, six
phytosterols have been found: 3,5-stigmastadien, β-sitosterol, 3,5-stigmastadien-7-one, brassicasterol,
avenasterol and campesterol (Clément et al., 2010; Esparza et al., 2015; Valentova et al., 2006).

Flavonoids and phenols

The tubers of the plant contain the flavanoles: catechin, epicatechingallate, gallocatechin and
epigallocatechingallate, the O-methylated flavon, tricin, and two of its flavonolignan derivatives, and the
lignane pinoresinol (Bai et al., 2015; Campos et al., 2013; Sandoval et al., 2002). However, Sandoval et
al.(2002) found that the contents of catechins were not high (2.5 mg catechins/g dry matter). Mandelic
acid, 3,4-dihydroxybenzoic acid and p-coumaric acid have also been found in the hypocotyl (Campos et
al., 2013; Sandoval et al., 2002) as well as p-coumaric acid and malic acid benzoate in the root (Bai et al.,
2015).

Other substances

Piacente et al. (2002) reported levels of benzylisothiocyanate and 3-methoxybenzyl isothiocyanate in a

root extract. The substances are potential degradation products of glucosinolates. Sun et al. (2018)
found that the content of essential oils in dried hypocotyls was 0.007-0.010 % in samples of yellow, red
and black maca (cultivated in China above 4 000 m). The constituents were not quantified but based on
the chromatograms. It looks as if benzenacetonitrile, benzylisothiocyanate and 3-
methoxyphenylacetonitrile may constitute a significant part of the oil.

In vitro studies
DTU FOOD has considered the in vitro studies that have examined the effects on sex hormones and
receptors for these hormones are the most relevant for the risk assessment of the root from L. meyenii.
Some other in vitro studies have examined the viability of cells, but they are not relevant to the risk
assessment and are therefore not reviewed.

Gao et al. (2019) investigated substances from a methanol extract of dried roots and rhizomes. In the
extract, ten substances were identified with HPLC analysis. Testosterone levels were measured in the

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Leydig cells (TM3 cells) of mice after exposure to each of the ten substances. There was an increased
level of testosterone following exposure to the macamide, benzylhexadecanamide, at concentrations
between 62.5 and 250 µg/ml.

In another study, the powdered root tuber was extracted with chloroform, methanol, ethanol or hexane
and all four extracts were studied in the DU 145 cell line, an androgen-independent prostata cell line.
None of the extracts showed an effect on the androgen receptor at concentrations up to 50 µg/ml
(Bogani et al., 2006).

Animal experiments
DTU Food has reviewed the published animal experiments. A review and description of all relevant
experiments are shown in Appendix 1, tables 1-4. DTU FOOD notes that in some studies the statistical
tests used following the analysis of variance (e.g. Least Significant Difference Test (Yu et al. 2020), Tukey’s
test (Valdivia Cuya et al., 2016) or Scheffe’s test (Rubio et al., 2006)), compared all groups with each
other, including the control group. The statistics used in these studies are therefore not the most
appropriate for a safety assessment. In toxicological studies, it is relevant to compare the dosed groups
with the control group for which Dunnett’s test is typically used.

Toxicokinetic Studies (ADME)

Two studies on toxicokinetics have been found in the literature review (see Appendix 1, table 1).

Yang et al. (2018) isolated a mixture of the imidazole alkaloids lepidiline A and lepidiline B from maca
powder. This mixture was administered orally to male mice at a dose of 5000 mg/kg. Various organs
were studied after 0, 1, 2, 3, 4, 6, 10 hours. Lepidiline A and lepidiline B were distributed mainly to the
liver, followed by the kidneys, heart and lastly the spleen. In the liver, the amount of lepidiline A and
lepidiline B metabolites decreased significantly after 4 hours, in the kidneys, heart and spleen after 3
hours.

Zhang et al. (2017) examined the distribution of the macamide, N-3-methoxybenzylpalmitamide, in rats.
Rats (sex not specified) were dosed orally with 80 mg N-3-methoxybenzylpalmitamide/kg body weight
and blood samples were taken after 0, 0.08, 0.16, 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 hours. The highest
concentration of the macamide was measured in the stomach, followed by lungs > spleen > brain, heart,
kidneys, liver and reproductive organs. The maximum concentration of macamide in blood plasma (600
ng/ml) was measured after 30 minutes and the half-life was 7.4 hours.

Both studies show that metabolites of constituents of maca, the alkaloids lepidiline A and lepidiline B,
and the macamide N-3-methoxybenzylpalmitamide, are distributed to several organs in mice and rats.

General toxicology

DTU FOOD has reviewed the literature and found a number of studies that investigate different
toxicological effects. DTU FOOD has assessed that the animal experiments performed by Meissner et al.
(2006a) included most parameters and is most relevant to the risk assessment. Therefore, this study will
be described in more detail, while other studies have been reviewed in Appendix 1, table 2. The study

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has been performed with a design closer to the OECD guidelines for 28- and 90-day animal studies than
any of the other published studies, but still has some shortcomings in fully following the OECD guidelines.

The used roots from L. peruvianum (a synonym for L. meyenii) were harvested in the Junin area of Peru,
located at an altitude of 4200 m and 4500 m above sea level. The maca roots represented the typical
distribution of three ecotypes (out of 13 known): black, yellow and purple/red roots observed in this
growing area. The roots were dried for three months and Dr. Gloria Chacon verified the authenticity of
the roots. After cleaning (washing under pressure) and cutting, the dried roots were added to water
before being subjected to a process of gelatinisation under pressure and high humidity, followed by
drying and powdering. The powder was chemically characterised for its contents of protein,
carbohydrates, vitamins, etc.

Sprague-Dawley rats (9-week-old females and 12-week-old males) were used. A 28-day and a 90-day
study was carried out. In both studies, the rats were dosed for 5 days a week. In the 28-day study there
were 5 male and 5 female rats in each dose group and in the 90-day study 10 male and 10 female rats in
each dose group. In both studies, the rats were orally dosed (by gavage) with water (control) or powder
(dissolved in 15 ml water) at doses of 750 and 7500 mg/kg body weight.

There were no deaths in the 28-day study. Results from the 28-day study showed that male rats lost 8.6
% of their weight (750 mg/kg) and 14.7 % (7500 mg/kg) compared to their initial weights, whereas the
control group increased their weight by 2.9 %. These weight reductions were statistically significant
compared to the control group. There were no differences in initial and end body weights for the
females in both dose groups compared to the control group.
Experimental results are not shown separately for males and females, only pooled values for the
hematological studies and for the clinical chemical studies are shown. The only exception is for
measurements of different sex hormones, which are shown for males and females separately. The authors
argue that data was “pooled” because there was a similar pattern in data from male and female rats. There
was an increase in concentrations of white blood cells in the lowest dose group (750 mg/kg) and a
corresponding increase in the highest dose group (7500 mg/kg) compared to the control group (both
measurements were just exactly not reaching statistical significance (p=0.06)). There was a statistically
significant increase in the number of lymphocytes in both dose groups compared to the control group. The
highest dose group showed a statistically significant increase in red blood cell decomposition and an
increased average cell volume of red blood cells compared with the control group. In addition, the number
of red blood cells and haemoglobin concentrations were reduced in the highest dose group compared with
the control group with a significance level close to statistic significant (p=0.06). It should be noted that,
compared with the clinical chemistry described in OECD guideline for a 28-day study, a number of
measurements are lacking: e.g. urea, bile acids and at least two parameters relevant to the assessment of
possible liver damage e.g. ALAT (alanine aminotranserase), ASAT (aspartate aminotransferase), gamma-
glutamyltranspeptidase or alkaline phosphatase. The concentration of triglycerides was significantly lower
in the highest dose group compared with the control group and the concentration of cortisol was
statistically significantly lower in both dose groups compared with the control group. Estradiol levels in
females were statistically significantly increased (136 pg/ml) in the highest dose group compared to the
control group (34.6 pg/ml). No differences were found in the levels of prolactin, FSH (the follicle stimulating
hormone), LH (the luteinising hormone) and progesterone in the females, PSA (prostate specific antigen) in
the males or TSH (the thyroid-stimulating hormone) between dosed groups and control groups. According
to the authors, no changes have been observed in the histopathological examination of different tissues
from male and female rats in the dosed animals as compared with the control group. DTU FOOD notes that
no histopathological examination were performed of the liver in male rats in the lowest dose group and of
the following organs: liver, pancreas, spleen and kidney in female rats in the lowest dose group. Based on
the description, there is inflammation of the prostate in the dosed groups, which is not described in the
control group. Renal inflammation are described in the female control group and in the lowest dosed male
group, whereas there are no such changes in the male control group. DTU FOOD also notes that the numbers
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of animals with the changes in question are not given.

There were no deaths in the 90-day study. There were statistically significant differences in the body
weight gains of the dosed male rats compared with the control group. In the lowest dosed group, male
rats lost 8.6 % in comparison with control animals gaining 20 % weight. In the highest dose group, the
animals increased their weight by 14.3 %, which was lower than the control animals (20 %). In females
there was a significantly lower weight gain (8 %) in the highest dose group compared to the control
group (25 %).

Also in this study, the authors “pooled” results for males and females from studies of hematology and
for clinical biochemistry instead of showing results for the two sexes separately. There were no
differences in hematological data of the dosed groups compared to the control group. A number of
biochemical measurements are lacking in relation to the OECD guideline for a 90-day study (the same as
in the 28-day study). The biochemical measurements showed that the glucose level in the highest dose
group was statistically significantly increased compared to the control group. The potassium level was
statistically significantly lower in the highest dose group compared to the control group. The same
hormones as in the 28-day trial were measured. The cortisol level in the lowest dose group was
statistically significantly lower than in the control group. In addition, progesterone in the female rats
was statistically significantly increased compared to the control group.
According to the authors, there were no differences in histopathological changes in various organs of the
dosed groups compared to the control group. DTU FOOD notes, however, that in in the females the
kidneys of both dose groups had infiltration of lymphocytes in the kidney cortex and increased lumen in
nephrites (which is probably the kidneys, but it is not a commonly used term), while histopathological
changes in the control group of the female animals have not been described. In males something similar
is seen in the lowest dose group, while the highest dose group has not been studied. However, here
changes in the control group are also described, but they are different from what is seen in the dosed
males.

The authors write that the 90-day study is performed in accordance with OECD guideline no. 408.
However, DTU FOOD notes that there are many deviations from this guideline, e.g. animals should be
weighed once weekly, the feed intake should be determined weekly and organs should be weighed at
termination. As already mentioned, several biochemical measurements of importance for assessing liver
or kidney injury are lacking. Histopathological examination of some selected organs has been performed,
but far less than recommended in OECD guidelines for a 90-day study. It is difficult to assess the
significance of tissue changes as the number of animals with changes in the individual dose groups is not
specified, which is not a normal practice. Two dose groups have been used in the study, while the OECD
guideline recommends three dose groups. Data for hematological and biochemical analyses of blood
from both the 28-day and 90-day study have not been shown separately. Male and female data are
pooled into one dataset. DTU FOOD notes that it is highly unusual and does not follow the OECD
guideline. It is relevant to show data for males and females separately, as there may be gender
differences in sensitivity to the test material.

The study shows that the dosing with the roots affects normal growth, which in the males are significantly
lower in both dose groups than in the control group. In the 90-day study, there is also less growth in
females in the highest dosed group. In addition, the administration affects the hormones, including, an
increase in the sex hormones estradiol and progesterone in female rats. In addition, in the 90-day study
changes in the kidneys of the females are observed, which are not seen in the control group. However,
the interpretation is difficult, because renal changes with inflammation have also been described in the
female rats of the control group in the 28-day study and the number of animals with changes is not
specified.

There is one other study (Chung et al. 2005) (Appendix 1, table 2-4), which shows reduction in body
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weights, while other animal studies do not show any effects on body weights.

Effects on the thyroid gland

Because glucosinolates are found in L. meyenii and it is well-known that glucosinolates may have an
effect on the normal function of the thyroid gland (Cooper & Johnson, 1998), DTU FOOD studied
whether such effects have been observed in animal studies. Various changes have been observed in the
level of thyroid hormones: TSH (thyroid-stimulating hormone), T3 (triiodthyronine) and T4 (thyroxine) in
a study in which racehorses (stallions) had been fed daily for 30 days with standard feed (control) or
standard feed supplemented with 50 or 75 g powdered root from L. meyenii (equivalent to 104 mg/kg
body weight or 157 mg/kg body weight, respectively) (Bilal et al., 2016) (see Appendix 1, table 2). It is
not possible to interpret a possible effect on thyroid hormone levels measured before and after feeding,
as it is expected that the measurements in the same groups were similar before and after feeding, which
they are not in the experiment. It would have been more relevant for the safety assessment if hormone
levels were measured in the blood samples before the beginning of the study (day 0) in the same way as
done for other parameters such as clinical chemistry and hematology. In other studies, a decrease in
TSH, but no effect on T3 or T4, were observed after dosing female rats with 500 mg dried roots/kg body
weight per day for 28 days (Meissner et al., 2006b), while no effects on TSH were observed in a study in
rats receiving up to 50 % maca powder in the diet for 7 weeks (Uchiyama et al., 2014). It will require
other and better studies of the hormone levels and eventually other studies to clarify whether maca has
an effect on the thyroid gland.

Effects of sex hormones, reproductive organs and mating behaviour

A number of studies have described the effects on reproductive parameters, including measurements of
sex hormone levels after dosing with L. meyenii in both males (Appendix 1, table 3) and females
(Appendix 1, table 4). In addition, there are some studies of male mating behaviour (Appendix 1, table
3). As described in Appendix 1, these studies have some limitations in terms of study design, study
description and statistics. In the following, there will be a shorter review of significant findings from the
studies in males and females.

Males

Gonzales et al. (2006a) (for more information see Appendix 1, table 3), studied the effects of aqueous
extracts of hypocotyls in different colours (black, red and yellow) dosed orally (equivalent to 0 and 1660
mg hypocotyls/kg body weight per day) to male rats for 7 or 42 days. Different types of effects were seen
with the different colour types. The only colour type that affected organ weights was the red maca that
reduced the weight of the ventral prostate after 42 days of dosing, while all colour types affected the
length of different stages of spermatogenesis after 7 days in various ways. Black maca also affected the
length of other stages, while black and yellow maca also affected the length of the last stage of
spermatogenesis after 42 days. Black and yellow maca affected the sperm concentration in the
epididymis after both 7 and 42 days.

Dosing with red maca for 7, 14 and 42 days (2000 mg/kg body weight) resulted in a reduction of the

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ventral prostate weight compared to relevant control groups, while there was no effect on prostate
weight after dosing with yellow and black maca for 7 days (these two colour types were not studied after
longer dosing) (Gonzales et al., 2005).

The same research group has in other experiments studied various preparations of the root (sometimes
different colours) orally administered to male rats. These studies have reported effects (most often
increases, but decreases are also described) on the sperm count (number of sperm per ml), when
isolated from the epididymis (e.g. Chung et al. (2005); Gasco et al. (2007); Gonzales et al. (2003b);
Gonzales et al. (2013); Yucra et al. (2008)). Effects on different stages of spermatogenesis (development
and maturation of sperm cells) have also been observed after 7 days of dosing or more (e.g. Chung et al.
(2005); Gonzales et al. (2006b); Gonzales et al. (2001); Gonzales et al. (2013)). Often, no weight changes
in the reproductive and accessory reproductive organs have been observed other than the reductions in
weight of the ventral prostate (Gonzales et al., 2005), while Gonzales et al. (2001) measured increased
weight of testes and epidydimedes. In studies, where measurements of testosterone levels have been
performed, levels are often not affected, but Chung et al. (2005) found decreased levels at some doses
as well as decreases in the ratio of estradiol to testosterone at the three highest doses.

The mentioned studies and additional studies mentioned in table 3, appendix 1, indicate that maca
hypocotyl or root may affect reproductive and accessory reproductive organs, spermatogenesis and/or
sperm count in male rats dosed with different preparations and colour types of L. meyenii root. The
effects point mainly to an androgenic effect.

Other studies of effects on male reproductive parameters also show effects indicating an androgenic
effect. Ohta et al. (2016) measured increased testosterone levels in male rats and increased weight of
seminal vesicles after dosing with a commercial maca powder (1000 mg/kg body weight) for six weeks.
Onaolapo et al. (2018) measured increased body weights and increased testosterone levels in mice
blood plasma after oral dosing with commercially available maca capsules at doses of 500 and 1000
mg/kg body weight for 28 days.

Studies (Appendix 1, table 3) show that dosing with maca results in increased sexual behaviour in male
animals (Cicero et al., 2001; Cicero et al., 2002; Lentz et al., 2007). DTU FOOD considers that increased
sexual behaviour is an adverse effect.

Other studies in experimental animals (Appendix 1, table 3) also show various effects, while some
studies do not find effects. Many different preparations of maca and different doses have been used in
the studies, so it is not surprising that not all studies show effects or the same type of effects. There are
shortcomings and limitations in the published studies, but the general finding is that various extracts of
maca from hypocotyls, tubers or roots, etc., as well as commercial products thereof, can have an
androgenic effect. Such an effect has also been observed in an in vitro study where increased levels of
testosterone were found after exposure to the macamide, benzylhexadecanamide. DTU FOOD considers
an androgenic effect as an adverse effect.

Females

The various studies of measurements of sex hormones, weight of reproductive organs, etc. after dosing
with the root of L. meyenii are examined in Appendix 1, table 4. In the following, a brief review of the main
findings is given.
These studies have been carried out both in intact females and others who were ovariectomised i.e. have
had the ovaries removed. The result of ovariectomisation is that the animals no longer have an oestrous
cycle and that levels of sex hormones change compared to animals with intact ovaries.
Several studies suggest that L. meyenii may affect the endocrine system in female animals. For example,
11
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a decreasing level of FSH has been observed in both dosed groups of ovariectomised female rats dosed
for 28 weeks with an ethanol extract of the root of L. meyenii (0.096 or 0.24 g/kg bw) compared to an
ovariectomised control group. In the lowest dose group, there was also an increase in estrogen
(estradiol). In a study by Meissner et al. (2006b) there was a decrease in estradiol levels in both intact
and ovariectomised female rats after 28 days of dosing with an aqueous extract of the root.
There is one study in which no weight changes of the uterus have been shown in ovariectomised rats
dosed with an ethanol extract of the root (Zhang et al., 2014). In two studies where ovariectomised
female mice received aqueous extracts of hypocotyls (three different colour variants) for 21 days and 42
days. respectively, there was a significant increase in uterus weights compared to the ovariectomised
control group (Rubio et al., 2006; Ruiz-Luna et al., 2005). In the study of Rubio et al. (2006) there was a
doubling of uterus weights after dosing with all three colour variants of the root. Such weight gain in
uterus in ovariectomised females suggests that L. meyenii may have an estrogen effect. In the study of
Ruiz-Luna et al. (2005) there was also earlier vaginal opening in female mice, whose mothers were
dosed with an aqueous extract of hypocotyls of maca. This can be a sign of an estrogen effect. The
authors attribute it to an effect of better nutrition, because it was only seen in female mice from litters
below a certain size. Whether one or the other explanation is right cannot be determined because the
offspring was not weighed.

In studies with female animals (with or without ovaries) dosed with different preparations of L. meyenii
roots observed effects indicate an estrogenic effect, and in other studies effects indicating other effect
on the normal levels of sex hormones have been observed.

Summary of animal testing

The study of Meissner et al. (2006a) including both a 28-day and 90-day studies, shows that dosing with
dried gelatinised roots of L. meyenii affects normal growth in male rats, so body weights are significantly
lower in the dosed groups compared to the control group. In the study, two dose groups have been
used and there is an observed effect at the lowest dose group. DTU FOOD considers that based, on the
data available from this study, no limit can be established for the intake of the root, below which the
intake will be without risk of adverse effects.

A number of studies have examined effects on reproductive parameters including changes in sex
hormones in male animals after dosing with various extracts of L. meyenii from hypocotyls, tubers or
roots, etc., as well as commercial products. Part of the studies show different types of effects. Some
studies show that the root of maca may affect the reproductive and accessory reproductive organs,
spermatogenesis and/or sperm cell count in male rats. The effects suggest an androgenic effect.

DTU FOOD considers that based on these studies, no level can be established under which the intake will
be without risk of adverse effects.

A number of studies have been performed on possible effects on reproductive organs and sex hormones

12
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in female mice and rats after dosing with various preparations of the root of L. meyenii. In addition,
experiments in ovariectomised female mice and rats no longer having an oestrus cycle have been
conducted. Some of these studies have after dosing with maca observed changes in levels of sex
hormones: estradiol, FSH, LH, progesterone and testosterone, and in some cases also weights of uterus in
ovariectomised mice, as evidence of changes in hormone levels.
These changes are not seen in the control groups which have not been administered maca. Overall,
animal studies indicate that dosing with the root and preparations herof may affect the normal level of
sex hormones in females. DTU FOOD considers such changes as adverse effects. Based on the animal
studies described, it is not possible to establish a dose under which these effects are not seen.

Human studies
Human studies are described in Appendix 1, table 5.

Hormone levels

Six studies have investigated the effects of administration of L. meyenii (maca) on hormone levels. Five
studies have studied the effect of maca on peri- and postmenopausal women (Brooks et al., 2008;
Meissner et al., 2005; Meissner et al., 2006c; Meissner et al., 2006d; Meissner et al., 2006e) and one
study has studied the effects on men (Gonzales et al., 2003a). Gonzales et al. (2003a) found no effects of
maca at the levels of progesterone, testosterone, estradiol, FSH, LH and prolactin in men administered
up to 3 g maca per day for 12 weeks. The results of the five studies examining the effect of maca on peri-
and postmenopausal women (Brooks et al., 2008; Meissner et al., 2005; Meissner et al., 2006c; Meissner
et al., 2006d; Meissner et al., 2006e), do not produce results pointing in the same direction, although
several of the studies are carried out under comparable conditions and with the same kind of maca
supplementation. This applies to measurements of LH, FSH, PG (progesterone), thyroid hormones,
cortisol and ACTH (corticotropin). DTU FOOD notes that the results of Meissner et al. (2006d) is a
repetition of results from Meissner et al. (2006c). These results from Meissner et al. (2006d) is,
therefore, not included in this assessment. In three of the studies, serum estradiol levels were higher in
women, who had received maca (2 g per day) for 1-2 months, compared to placebo (Meissner et al.,
2005; Meissner et al., 2006c; Meissner et al., 2006e), while it remained unchanged, probably due to too
few participants, after administration of 3.5 g maca per day for 6 weeks (Brooks et al., 2008). Due to the
few participants (n = 7-18) and significant differences in the level of estradiol between the groups at the
beginning of the interventions, the uncertainty is high.

A case of prolonged intermenstrual bleeding has been reported after intake of an unknown dose of maca
(Srikugan et al., 2011). Based on the abovementioned studies DTU FOOD considers that it cannot be
excluded that 2 g maca per day taken as a food supplement may affect hormone levels in peri- and
postmenopausal women.

Liver damage

Maca-induced liver injury has been reported as an adverse reaction in a 30-year-old man following the
intake of 300 ml of Maca medicinal liquor with 50 % (V/V) alcohol (Xiao et al., 2017). The real dose of
maca in the product is unknown. An elevated level of aspartate aminotransferase (ASAT) were observed
in the 30- year-old male as well as in a study conducted by Valentova et al. (2008) after dosing of 0.6 g
maca per day for 90 days to patients with metabolic syndrome. A review of the U.S. National Library of

13
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Medicine (NIH, 2019) concludes that maca is unlikely to cause clinical liver damage at doses of 0.5-3 g per
day.

Side effects

A number of studies report side effects from the gastrointestinal tract and headache associated with maca
interventions (up to 3 g per day) (Corazza et al., 2014; Dording et al., 2008; NIH, 2019).

Miscellaneous

Reduction in body weights in women after intake of 2 g maca per day were observed in two studies
(Meissner et al. 2006b, 2006c) while one study did not find an effect after 3.5 g maca per day (Brooks et
al., 2008).

14
Appendix 1.

It is not generally indicated in the tables which statistics are used in the surveys unless statistics have been used, which the DTU FOOD does not
consider to be the most optimal.

Table 1: Toxicokinetics (ADME (Absorption, Distribution, Metabolism and Elimination))

Abbreviation used: bw: body weight.

Plant part Extraction Chemical identification Animals, doses and Endpoint Outcome Comments
dosing Reference
L. meyenii 95 % etanol and Fat-soluble and water- Male mice (strain: ADME Lepidiline A and lepidiline B were Yang et al.
powder. subsequently fractioned. soluble alkaloids were Kunming, n=5 per time (2018)
group). Oral 5000 mg/kg
bw. The heart, liver,
spleen and kidneys
. isolated from the powder were sampled after distributed mainly to the liver,
(lepidiline A (1,3- dibenzyl- after 0, 1, 2, 3, 4, 6, 10 followed by the kidneys, heart and lastly to
2,4,5-trime hours.
thylimidazolechloride) and the spleen. In the
lepidiline B (1,3-dibenzyl- liver, the amount of metabolites
4,5- dimethylimidazole
chloride). of lepidiline A and lepidiline B-
decreased significantly after 4
hours, in the kidneys, heart and
spleen after 3 hours.
N-3-methoxyben- N-3-methoxybenzyl UP LC MS/MS method. Rats (strain: Sprague- Distribution Maximum Gender not Zhang et al.
specified.
zyl-palmitamide palmitamide Dawley) orally at concentration (600 ng/ml) in blood (2017)
plasma was
(macamide in was 80 mg/kg, n=6. Analyses measured at 0.5 hours and
maca) from manufactured to performed for up to 48 the half-time was 7.4 hours. The
Sinopharm the animal study hours after dosing. highest concentration was
Chemical Reagent by chemical measured in the abdomen, followed by
Co. Ltd., China. synthesis. lungs > spleen > brain, heart,
kidneys, liver and reproductive
organs.
DTU
Table 2: Acute, subacute and subchronic animal studies (general toxicity)
Abbreviations used: GGT gamma-glutamyl transpeptidase, bw body weight, TSH thyroid-stimulating hormone, T3 triiodthyronine and T4 thyroxine.

Plant part Extraction Chemical identification Animals, doses and Endpoint Outcome Comments
dosages Reference
Dried L. meyenii, 95 % ethanol. The extract contained Acute toxicity: Male and Acute toxicity, Acute toxicity: No effects, LD50 Statistics: Least Yu et al.
powder from 756.62 mg macamides/100 g - female mice (strain: Ten subchronic toxicity. >2000 mg/kg bw. Significant Difference (2020)
hypocotyls from analysed with HPLC. Kunming, n=10) orally Subchronic toxicity: No effects Test following the
the company Bai- by gavage, twice within observed (bodyweights, relative analysis of variance.
SuiFang Co. Ltd, four hours, 2000 mg/kg organ weights, feed intake, This test compares all
Yunnan, China. bw. Mice observed for water intake, hematotology and dose groups with each
14 days. Subchronic: clinical chemistry. other, including the
Male and female mice, control group.
(strain: Ten Kunming
n=10) orally, twice
within four hours (200,
500 and 1 000 mg/kg
bw.) daily for 45 days.

Yellow maca tubers Two extracts: Both extracts were analy- Body weights. No effect. Two of the authors Zheng et al.
Male mice (strain:
from Anhui 95 % etanol (raw serated with a chromatogra- were employed by (2018)
Kunming, n=10) orally
Sunshine Phar- extract). 25 % fish method and in both Anhui Sunshine
for 28 days.
maceutical Co., Ltd etanol (purified extracts 8 different macamides Pharmaceutical Co., Ltd
Raw extract: 30 and
(Bozhou, China). extract), this were quantifiable (Bozhou, China), which
120 mg/kg,
extract was supplied the maca
corresponding to 0.14
fractionated. tubers.
and 0.57 mg/kg of
macamides.
Purified extract: 8 and
32 mg/kg,
corresponding to 0,14
and 0.55 mg/kg of
macamides.

Water. Fractioned Polysaccharides measured by Male mice (strain: Body weights. No effect on body weights. Like et al.
L. meyenii, tubers
to a high content the RSM method. Kunming) orally with (2018)
from the company of polysac- gavage (150, 300 and
Yantai, ShanDong, carids in the 600 mg/kg bw.) for 30
China. The plant is extract. days, n=5-6.
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grown in China.

17
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L. meyenii, root Petroleum ether. Male mice (strain: Body weights. No effects on body weights of the Yang et al.
from Lijiang The extract yield Balb/c) dosed orally various macamides. (2016)
BaiSuiFang Bio- was 1.96 %. with extracts of 12 and
technology De- 40 mg/kg of N-benzylli-
velopment Co. Ltd. noleamide, 12 and
Yunnan, China. 40 mg/kg of N-benzyl
oleamide or 12 and 40
mg/kg of N-
benzylpalmitamide for
14 days, n=10.

Not specified. Maca The content of macamides in Male mouse (ICR strain, Body weights. No differences in body weights No statistics have been Guo et al.
powder (L. meyenii) the powder was measured 14 months old). Daily were found between the dosed applied on body (2016)
imported from with HPLC and compared with dosing by gavage for 5 group and the control group. weights.
Peru. The authors standard maca products from weeks. However, nothing
have received the Peru. Similar levels of Control: (n=7) received suggests an effect
powder as a gift macamides were found in the the same volume based on Figure 2,
from Nanjing Bio- used powder compared to physiological saline as which shows body
Array Technology other maca products. the dosed group. Dosed weights relative to the
Company, China. group (n=7): maca time in weeks.
powder (500 mg/kg
bw.) in a physiological
saline suspension.

Powdered Eighteen racehorses, Clinical chemistry M75 (day 45): gamma-glutamyl Differences in thyroid Bilal et al.
organically grown (stallions, average age was carried out on transpeptidase (GGT): ↑, Mg: ↓ hormones are observed (2016)
root from maca (L. 6.5 years, average blood samples M50 and M75: (day 30, 60 min. in the different groups,
meyenii) imported- weight 478-480 kg, from days 0, 30 after feeding): insulin ↓ e.g. reduction in TSH
by Dogaform Gida n=6). The study lasted and 45 and he- M50 and M75: (day 30, prior to prior to feeding in both
Sanayii, Turkey. for 45 days The control matological studies feeding): TSH ↓. dosed groups. The
group: ordinary feed; on blood samples authors have
taken days
0 and

18
DTU M50 group: ordinary 45. On blood M75: (day 30, all time points not published the levels
feed + 50 g maca samples from day after feeding): T3 ↑ and T4 (30 of TSH, T3 and T4 or
powder, M75 group: 30 were examined: minutes after feeding): ↑. Body any other hormones
ordinary feed + 75 g ghrelin, adipo- weights, the average daily feed from a sample prior to
maca powder. The nectin, leptin, intake and hematological data the beginning of the
horses were fed twice a insulin, TSH, T3 were unaffected by maca study. In contrast to
day. 50 g maca for a and T4. Hormone feeding. clinical chemistry and
horse (478 kg) ~ levels were the hematology, where
104 mg/kg bw. 75 g examined it is possible to
maca ~ 157 mg/kg bw. 60 minutes before compare with a 0-
feeding and 15, 30, sample. There are no
60, 120 and 240 data on the
minutes after glucosinolate content
feeding. of the maca powder
used. The authors refer
to their previous
experiments in which
the feed (energy
intake, protein, zinc
and copper) have
affected the hormones
of the thyroid.
According to the
authors, high levels of
GGT are seen in
diseases of the
kidneys, liver and
pancreas, but they
refer to the fact that
the levels of GGT and
Mg are in the normal
ranges for horses.
After the analysis of
variance, differences
between all groups
were determined by
“Tukey
Multiple Range test”.

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Roots (mixture of Gelatinisation
yellow, black and process with
red colour types of water.
L. meyenii from the
Junin region of
Peru).
This test compares all
groups with each other
including the
control group
Acute toxicity study 1: Acute toxicity: Acute toxicity studies 1 and 2: Meissner et
Rats (strain: Wistar) and clinical No deaths of the laboratory al.
mice (strain: Swiss), observations. animals reported. The authors (2006b)
males and females, concluded that the LD50 for
n=5: 2000 mg/kg bw, mice is > 15 g/kg bw and > 5 g/kg
orally (by gavage), bw for rats.
observed for 14 days.
Acute toxicity study 2:
Male rats dosed orally
with 500, 1000,
2000 and 5000 mg/kg
bw and male mice
with 1000, 5000,
10000 and 15000
mg/kg bw orally,
observed for 72 hours
for clinical signs of
toxicity.
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Table 3: Effects on sex hormones, reproductive organs and mating behaviour in male animals
Abbreviations: I.m. intramuscular, LH luteinising hormone and bw body weight.

Plant part Extraction Chemical identification Animals, doses and Endpoint Outcome Comments
study design Reference
L. meyenii roots 95 % etanol. The extraction yield was Male and female mice No effects on male mating Zhang et al.
collected in 1.05%. Screened for ten (strain: Balb/c). Males Body weights. behaviour, the relative organ- (2019)
Yunnan, China. macamides and macaenes. (n=10) were orally Mating behaviour, weights of the reproductive
Four substances were dosed with extract 200 weights of male organs or testosterone level.
detected (4.51 mg/g). The four mg/kg bw daily for 14 reproductive
substances: (9Z,12Z,15Z)- days. After dosing males organs (testes,
octadecatrienoic acid, were mated with the seminal vesicles,
(9Z,12Z,15Z)-N- females. preputial glands
benzyloctadecatrienamide, and epididymedes)
(9Z,12Z)-octadecadienamide and testosterone
and (9Z,12Z)-N- level.
benzyloctadedienamide.
Dried hypocotyls Aqueous extract Male rats (strain: Body weights, No effect on body weights (7 and Following the analysis Gonzales et
from three eco- Holzman, 4 months old, organ weights 42 days). Red maca: ↓ prostate of variance, differences al. 2006a
types (black, yellow n=6), orally (by gavage), (testes, weight after 42 days of dosing were determined with
and red) of L. 0 (water, control group) epididymedes, compared to the control group Scheffe’s test.
meyenii from Car- or 1 660 mg/kg bw for 7 ventral prostate, All three colors of maca affected This test compares all
huamayo, Junin, or 42 days. kidneys, spleen, dose groups with each
the stages of spermatogenesis
other, including the
Peru. lungs and heart), after 7 days of dosing - the black control group.
stages of maca affected most stages. After
spermatogenesis. 42 days of dosing black and
Semen quality: yellow maca affected one stage
sperm count of spermatogenesis, while red
(epididymis), daily maca had no effect. Daily sperm
sperm production production in the testicle ↑ after
in testes and sperm 7 days of dosing with black and
motility. yellow maca and ↑ after 42
days with black maca.
Sperm cell count ↑ in

21
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the epididymedes ↑ after 7 and

42 days of dosing with black and
yellow maca compared to the
control group. After 42 of dosing
with black maca sperm motility
↑ whereas no effect of other
colour types were observed after
42 days of dosing and no effect
was observed after 7 days of
dosing regardless of colour type.

MacaxsTM from Water/ethanol. Study 1: Male rats (8 Body weights, Study 1: One rat died in the The authors write that Yoshida et al.
Towa Corporation weeks old, n=8) dosed food intake, maca group. The study showed mass of hair was found (2018)
K. K., Tokyo, Japan. with maca via feed (2 testes weights, that the younger rats (8-week- in the stomach at
Powder produced %) daily for 27 weeks testosterone old) who received maca in their autopsy of all the dead
by extraction of corresponding to levels in serum diet gained less weight in the animals.
dried maca roots. approximately 1300- (measured every last 7 weeks of dosing than the It is unusual that the
1700 mg/kg bw. A 6 weeks). control group. For three of these doses are not given in
control group (n=8) was weeks, the animals had a lower kg body weight per day
fed normal rat feed feed intake. After 6 weeks of (DTU has made an
during the same period. dosing, the levels of estimation). It is not
All rats were Wistar. testosterone ↑ in the maca normal practice and
Study 2: Male rats (18 group compared with the does not give an
weeks of age, n=13) control group. Such a difference accurate picture when
dosed daily for 30 was not seen at other time data on body weights
weeks with maca via points. and feed intake from
feed (2 %) daily for 30 Study 2: Two animals died in the animals dying during
weeks ) corresponding control group and two animals the study are excluded
to approximately 825- in the maca group. In fully from the data analyses
1200 mg/kg bw. A mature rats (18 weeks of age at on these endpoints. All
control group (n=12) the beginning of the study), surviving animals were
received regular feed there were body weight included in the
during the same period. differences between the maca measurements of
group and the control group testosterone levels and
during the following weeks after and testes weights.
the start of the study: 2, 5, 18,
26, 29 and 30. Maca had no

22
DTU
effect on testes weights and no
additional effect on serum levels
of testosterone in the two
studies.

500 mg capsules, The capsules were Male mice (9 weeks Body weights, Maca dosing (both doses): The mouse strain is not Onaolapo et
Maca root, from dissolved in old): 500 and testes weights, Increased body weights and mentioned. al. (2018)
Mason Natural®, water. 1000 mg/kg bw per day, testosterone level. testosterone levels in blood Statistics: Tukey’s
Florida, USA. orally for 28 days Histology of the plasma, higher sperm counts/ml honest significant
(n=10). testes and and increased percentage of difference (HSD) test is
morphometric sperm moving. No effect on used after the analysis
measurement in
testes weights or on tissue of variance. This test
the testes.
morphology histologically, but in compares all dose
morphometric measurement, the groups with each other,
dosing affected the widths of the including the control
seminiferous tubules that group.
became larger.

23
DTU
Macaxs TM from Powder produced Male rats (strain: Body weights, No effect on body weights. In the It is unusual that the Ohta et al.
Towa Corporation by extracting Wistar, 6 weeks old). feed intake, last two weeks, higher feed dose is not given in kg (2016)
K. K., Tokyo, Japan. from maca Dosing in the feed weights of intake in the maca group. In the bodyweight per day
‘bulbs’ (blend of with 2 weight percent testes, ventral maca group there was increased (DTU has made a
red, yellow and for six weeks, prostate and se- relative weight (i.e. organ estimation- based on a
black) with a corresponding to minal vesicles, weight/body weight) of seminal rats weight of 230 g).
mixture of water- approximately testosterone and vesicles, but no effect on relative One of the authors is
ethanol. 1400 mg/kg bw per day, LH levels in testes and prostate weights. employed by the
n=8. Controls (n=8) fed blood. Maca dosing ↑ testosterone company supplying the
normal rat feed. level in serum. No effect on LH. maca
powder.

Hypocotyls of Water. One gram Body weights and All three maca types increased The kidneys are not Gasco et al.
Male rats (Holtzman, 3 weighed or studied
black, yellow and of the dried organ weights of: sperm concentration in ductus (2007)
months old). histologically. However,
red maca from hypocotyls of reproductive deferens. The yellow and black
1000 mg/kg bw orally it is one of the
Peru. red, yellow and organs (testes, maca also in epidydimedes.
(by gavage) daily for 84 excretion organs (like
black maca epidydimedes, Dosing with maca had no effect
days, n=8. Control rats the liver) that are
yielded 0.40, seminal vesicles on bodyweights or organ
were dosed in the same normally weighed and
0.36 and 0.56 g and ventral pro- weights. No effect on the level of
way but with distilled examined histologically
freeze-dried state), as well as DNA in testes or apoptosis/ne-
water, n=8. to find possible harmful
aqueous extract. liver and spleen. crosis of DNA. No effects on the effects.
Different morphology of testes or liver in After the analysis of,
measurements of histopathological examination. variance, differences
sperm counts, The spleen was collected, but it were determined with
reproduction is not mentioned whether any Scheffe’s test. This test
parametres and- histological changes were compares all groups
quantification of observed in this organ. with each other,
DNA in testes. including the control
Histolological group.
examination of
testes,
epidydimedes and
liver.

24
DTU
Dried hypocotyls Aqueous extract. Sexually mature male- Hormone Maca affected the daily sperm Following the analysis of Gonzales et
from L. meyenii rats (strain: Holzman, 4 measurement of production, which was higher variance, differences al. (2006b)
(black variant) months of age, n=6) testosterone in day 7 compared with the control were determined with
from Peru. orally (by gavage), serum. group. The sperm cell count was Scheffe’s test. This test
2000 mg/kg bw per day Measurements of higher at some of the days up to compares all groups
for 1, 3, 5, 7 and 12 daily sperm day 7 in the epididymedes and with each other,
days. Control animals production, sperm ductus deferens, but no including the control
received water orally count per ml in difference was observed on day group.
(by gavage), n=6. epididymedes and 12. In the maca treated animals,
ductus deferens. the ratio between lumen and
Right testis and tissue in ductus deferens was
epidydimedes reduced day 7 but not day 12.
collected for
histology and
morphometry.
Dried hypocotyls of Aqueous extract. Two studies. Both are 1st study: Sex- 1st. study: It is not clear what is Gonzales et
L. meyenii including carried in adult male rats hormones The weight of the ventral pro- used as vehicle or al. (2005)
red, yellow and (Holtzman). (testosterone and stata ↓ with the red variant. which oil is used for
black variants, 1st study: Control oestradiol) in Yellow and black: No effect. injection. In study 1,
Peru. (vehicle n=35) or serum. Weights of: There were no other differences not all animals are
yellow, red or black L. testes, between the groups. included in the
meyenii (n=12). Dosed epididymedes, 2nd study: hormone
orally (by gavage) for 7 ventral prostate, Dosing in both 14 and 42 days measurements (n=10
days. Dosed groups seminal vesicles, with red maca (n= 6, 14 days, for the control group,
received extract kidneys, liver, n=7, 42 days) ↓ weights of the n=6 for the other dosed
equivalent to 2 g dried spleen, heart and ventral prostate compared with groups). The number of
hypocotyls per kg bw lungs. vehicle control (n= 13, 14 days animals are not
per day. 2nd study: As in and n=12, 42 days). described in the
2nd study: Included 8 study 1 (apart from Testosterone group: ↑ weight of material and method
groups. not measuring sex ventral prostate and ↑ weight of paragraph for study 2,
Four groups were dosed hormones), seminal vesicles. Red maca (n=6, but the number of
for 14 days, other four histology and 14 days, n= 5, 42 days) both days animals is mentioned
dosed in the same way quantification of ↓ in ventral prostate weight in together with the
for 42 days. Of the four tissue parts on the testosterone group (compared to different results.
groups, two were ventral prostate. testosterone control). In Study 2.
dosed with 0.1 ml of oil After 42 days of dosing: After the analysis of
intramuscularly (i.m.) quantitative analysis of variance, differences
and two were injected histological slides of ventral were determined using
with testosterone (0.1 prostate: ↓ at the height of the Scheffe’s test. This test
ml testosterone epithelium and ↑ lumen area in compares all groups
enanthate) (25 mg i.m.) rats receiving red maca compared with each other,
25
DTU on study days 1 and 7. with the control group (vehicle). including the control
One group (control No other differences among group.
group) received vehicle the groups were observed.
orally, the other
received red maca
(2 g/kg bw). The
testosterone treated
animals were either fed
orally with vehicle or
with red maca (2 g/kg
bw).

26
DTU

Hypocotyls of L. Aqueous extract. Sexually mature male Body weights, Reduced weight gain in the high Data from the study is Chung et al.
meyenii (yellow One gram of dried rats (three months organ weights of: dose group. No effect on organ poorly reported e.g. (2005)
type), Peru. hypocotyls old, strain: Holtzman), testes, weights other than seminal the number of animals
yielded 0.46 g of dosed orally (by epidydimedes, vesicles ↓ (100 and 1 000 mg/kg per dose group is not
freeze-dried gavage) for 7 days seminal vesicles, bw). There was a dose- mentioned. In a table it
maca. with 10, 100, 1000 liver, kidneys, dependent increase in the length is mentioned that
and 5 000 mg/kg spleen and lungs. of sperm stages VII-VIII in the testosterone levels
extract/kg bw per day. Measurements of testes. Sperm count/ml ↑ in the have decreased in two
Doses corresponded testosterone and three highest doses. dose groups, whereas
to 2, 220, estradiol in serum. Testosterone ↓ in groups that the authors only
2200 and 11 000 mg of Study of sperm received 100 and 1 000 mg/kg mentiond one in the
dried hypocotyls/kg bw quality: sperm bw. The ratio text.
per day. count in sperm testosterone/estradiol: ↓ in the
samples from the groups receiving the three
epididymedes, highest doses (100, 1000 and
sperm motility 5000 mg/kg bw. day).
histological
examination of the
testes.

27
DTU
Hypocotyls of L. Water/ethanol. The raw extract was fractioned Male rats (strain: Body weights, No effect on body weights and Following the analysis of Yucra et al.
meyenii (black va- Yields: 100 grams by ethyl acetate, n-butanol, Holtzman, 3 months weight gain, organ relative organ weights. The ethyl variance, Scheffe’s test (2008)
riant). of dried petroleum ether or chloroform old), 1000 mg/kg bw per weights of acetate fraction: ↑ daily sperm was used. This test
hypocotyls = 7.6 g with the following yield: day orally (by gavage) reproductive production. Ethyl acetate, petro- compares all groups
raw extract. petroleum ether (23.7 mg), for 7 days. Control organs (as relative- leum ether and chloroform- with each other,
The extract was chloroform (176.8 mg), ethyl groups received weight - organ fractions: ↑ sperm cell count in including the control
made by acetate (207.7 mg), n-butanol distilled water or epididymedes. group.
weight/body
Agroindustrial (2.46 g) and the residual distilled water added 1 weight): testes, Petroleum ether, etyl acetate
aqueous solution (25.93 g).
Chanchmayo, % dimethyl sulfoxide, epididymedes, and water fractions: ↑ sperm
The five fractions were tested
Lima, Peru. n=6. seminal vesicles count in vas deferens.
together with the raw extract.
and ventral pro-
state. Testis
functional
parameters as
daily sperm
production, sperm
count in
epididymides and
vas deferens.
Root of L. meyenii Aqueous extract. Mice (strain: Balb/c, 5-6 Semen quality: No effects of maca dosing on the The study included Valdivia
(yellow colour weeks of age, n=5), Sperm count in measured parameters. other groups of mice Cuya et al.
type), Peru. orally with 666 mg/kg semen from the whose fertility was (2016)
bw per day for 35 days epididymedes, reduced by chemical
and an untreated sperm mobility and and physical exposure.
control group. DNA This becomes
fragmentation in important when the
sperm cells. authors after the
analysis of variance
have used Tukeys test
since this test
compares all groups
with each other,
including the control
group.

28
DTU
Dried hypocotyls Water/ethanol The contents of polyphenols Male rats (strain: Body weights, In the maca group: ↑ daily- Poorly reported study. Gonzales et
from L. meyenii 60:40 (v/v). 100 and flavonoids were measured. Holtzman, 3 months organ weights of production of semen, ↑ number Dosing is not indicated al. (2013)
(black colour type) gram of dried old, n=6). reproductive of sperm cells/ml and increased in mg/kg bw. DTU has
from Peru. hypocotyls Intake: organs: testes, length of stages VII, VIII, IX-XI therefore calculated on
corresponds to approximately epididymedes, and XII in spermatogenesis. the assumption that
22 g of dry 200 mg/kg bw vesicula seminalis the rats weigh 250 g.
extract. daily orally (by and ventral Statistics: after the
gavage) for 7 days prostate. Semen analysis of variance,
The control group quality: sperm Scheffe’s test was used.
received distilled count, sperm This test compares all
water by gavage. production and groups with each other
assessment of the including the control-
length of different group (there are more
stages in groups in the study
spermatogenesis. than mentioned in this
table).

Maca (Natura-max Aqueous extract. Sexually mature male Mating behaviour The aqueous maca extract had There is no information Lentz et al.
S.A.C., 100 % rats (strain: Sprague- was examined a small effect of male sexual on the plant part used (2007)
natural). Dawley, weight: 250- after 1, 7 and 21 behaviuor in mature male rats and growing
350 g, n=11, sexually days of dosing after 1 and 7 days of dosing. conditions. including in
experienced). Control when males were After 21 days of dosing, there which country the
(distilled water). 25 or paired with a were no effects. plants were grown.
100 mg/kg bw/day receptive female.
orally (by gavage) for 30
days.

L. meyenii, root, Extraction with Sexually mature male Semen quality: Effects were observed on the Poorly reported. Gonzales et
from Peru. hexane followed by rats (strain: Holzman, 3 cell counts in length of different stages of Dosing is not indicated al. (2003b)
100 % ethanol. months old, epididymedes, spermatogenesis at both maca in mg/kg bw. DTU
weight: 295 g; n=6). stages in doses. The concentrations of made an estimation
Control: approximately spermatogenesis sperm cells in the epidydimedes assuming that the rats
2 ml day (5 % etanol) and testosterone were: ↑ after 7 days with both weigh 300 g.
orally. Other groups: level in serum doses, ↑ after 14 and 21 days of
approximately 160 or (only after 21 dosing with the low dose and ↓
320 mg/kg bw per day days). with the high dose after 14 and
orally for 7, 14 and 21 21 days of dosing. No effect on
days. the testerone levels

29
DTU
Root from L. Aqueous extract. Sexually mature male Weights of testes, Weights of testes and Badly reported and Gonzales et
meyenii from Peru. rats (strain: Holzman, 3 epididymedes and epidydimedes: ↑ poorly designed: the al. (2001)
months old, n=10). seminal vesicles, in the maca group. Dosing with mean weight of animals
Approximately 485 effects on maca resulted in a reduction in in the control group
mg/kg bw per day orally spermatogenesis. the lengths of stages II -VI and an (246 g) differs
for 14 days. The control increase in the lengths of the significantly (12 %)
group received vehicle. stages IX-XI and XII in the compared with the
spermatogenesis dosed group (275 g).
Dosing is not given in
mg/kg bw. It is
therefore calculated by
DTU on the assumption
that the rats
weigh 275 g.

L. meyenii, root 500 g powdered Rats (strain: Sprague- Different All three extracts of maca Poorly reported study. Cicero et al.
donated by roots were Dawley, 60 days old). parameters related affected different parameters in Dosing is not given in (2002)
Naturalfa Quimica extracted with Males (sexually to mating the mating behavior. The hexane mg/kg bw. It is
Suiza Lima, Peru. hexane, inexperienced) and behaviour. extract affected the most estimated by DTU on
chloroform or females (sexually parameters. the assumption that
methanol. experienced). The the rats weigh 250 g.
females were
ovariectomised and
oestrus was initiated
by subcutaneous
injection of estradiol
benzoate and
progesterone. Males:
orally (by gavagel): 0
(control),
approximately
208 mg/kg bw of the
hexane extract, 3480
mg/kg bw

30
DTU

of the methanol extract

or 96 mg/kg bw per day
of the chloroform
extract for five days.
Thereafter males were
housed with females in
oestrus.
Powdered root Rats (strain: Sprague- Body weights, No effect on body weights. Cicero et al.
from L. meyenii, Dawley, 3 months old, different mating Effects of different parametres in (2001)
standardised to (body weight males: behaviour male mating behaviour after
0.6 % macamides 240-260 g), n=20). Both parameters. both 1 and 15 days of dosing
and macaenes, males and the females with both doses. For several of
donated by Santi- were sexually the parameters measured, there
veri, Barcelona, experienced. The was a tendency to a dose-
Spain. females were dependent effect after 15 days
ovariectomised and of dosing.
entered oestrus after
subcutaneous injection
with estradiol benzoate
and progesterone.
Males: orally: 0
((control), saline by
gavage), or powdered
root: 15 or 75 mg/kg
bw per day for 15 days.
After 1 and 15 days of
dosing, the males were
housed with the
females.

31
DTU
Table 4: Effects on sex hormones and reproductive organs in female animals
Abbreviations used: ACTH corticotropin or adrenocorticotropic hormone, FSH follicle stimulating hormone, HDL high density lipoprotein, LDL low density
lipoprotein, LH luteinising hormone, TSH thyroid-stimulating hormone, T3 triiodthyronine and T4 thyroxine.

Plant part Extraction Chemical identification
Dried and The powder was examined
powdered root chemically by extraction with
tubers of L. petroleum ether, followed by
meyenii HPLC-UV-MS analysis. 12
purchased by the- macamides were identified
company Yamano and the chemical profile was
del Peru SAC. similar to what other papers
have described in tubers from
L. meyenii.
Animals, doses and Endpoint Results Comments Reference
design
Female rats (Sprague- Body weights, feed LH (the luteinising hormon) ↑ At the beginningof the Uchiyama et
Dawley) were included intake, oestrus dose-dependently in both the study, the rats are not al. (2014)
in the study from the cycles were highest and median dosed sexually mature. The
age of 21 days. The rats followed by groups. FSH (the follicle rats are purchased at
were randomised and examination of stimulating hormone) ↑ in the 14 days of age. Rats
divided into four vaginal smears. highest dose group. ACTH usually go at least to
groups. Study period: The animals were (corticotropin or day 21 with their
Seven weeks. A control euthanised in adrenocorticotropic hormone): mother before
group (n=20) was fed prooestrus after 7 ↑ in the highest dosed group. weaning. The
normal rat feed. Three weeks of dosing. No differences in the contents of powdered tuber
dosed groups received Measurements of somatotropin, TSH (thyroid accounts for up to 50 %
feed mixed with sex hormones in stimulating hormone) and of the feed, without
different percent maca blood samples prolactin. No differences in food taking into account
powder: 5 % (n=10), 25 collected during intake, weight gain, absolute whether the feed
% (n=10) or 50 % euthanasia where weights of ovaries, uterus, contains the same
(n=20). also non-specified hypothalamus and pituitary macro- and
At day 38 (study day 16) organs were gland between the control group micronutrients as the
all groups had the same removed. and the maca dosed animals. control feed. The
feed intake in and the absolute weights of
authors calculated daily four organs are
intake of powdered root reported. The
of 0 (control), 3.0 (5 % experiment is poorly
group), 15 (25 % group) described because it is
and 30 g/kg bw (50 % not known whether
group). more organs have been
collected than the ones
the authors describe.
Only data from the
highest dose group and
control group are
shown, but whether a
dose-response is seen
is of

32
DTU

toxicological interest.
No pathological studies
of the weighed organs
have been carried out,
neither by macroscopic
observation or micro-
skopically.
The powdered 95 % etanol. The yield of the extract was 50 female rats (Spra- Body weights and Body weights were unaffected in It is unclear how the Zhang et al.
roots/root tubers of 19.2 % (weight). The extract gue-Dawley, 90 days old weights of uterus. maca dosed animals. Uterine purchased root is (2014)
L. meyenii was further diluted with were divided into 5 Blood samples weights were similar in already standardized to
(standardised to distilled water to the final groups, n=10). Four of collected after 12 ovariectomised control and both a content of
0.6 % macamides concentrations. the groups were and 28 weeks of maca groups. 12 weeks: macamide/macaenes).
and macaenes) ovariectomised while dosing for Testosterone ↑ in the lowest
purchased from the 5th group was measurent of maca group compared to the
Lima, Peru, through intact (sham operated). estradiol, FSH and ovariectomised control After 28
Chinese Maya All groups were daily testosterone. weeks: Both maca groups: FSH
Bioengineer Co, orally dosed (by gavage) ↓, lowest maca group: estradiol
Hubei, China. for 28 weeks. Two ↑.
control groups (one
intact and one
ovariectomised)
received distilled water.
Two
ovariectomised groups
received extract of L.
meyenii (0.096 or 0.24 g
per kg bw).
The same study as No differences in organ weights The authors don't write Zhang et al.
in Zhang et al. 2014 of liver, spleen and adrenal gland that this is the same (2006)
but with other between the different groups study as Zhang et al.
samples taken. (See (data are not shown in the (2014), but it can be
further description paper). Serum calcium and seen from the identical
of this study above). inorganic phosphorus was body weights and
comparable uterus weights in the
between groups. two papers.

33
DTU
Apart from one
difference (error) in
data from a single
group showing lack of
care in the reporting
of weights.

Hypocotyls from L. Standardised The polyphenol contents were 36 female rats, three Weight of uterus. No change of uterine weights in The extract is poorly Gonzales et
meyenii - variants extract measured by a previously months old. The groups the three groups that received characterised. The rats al. (2010)
in 3 colours (black, (water/alcohol) described method (not consisted of: An intact maca compared to the relevant are most likely dosed
yellow or red), extracted from described in the present (sham operated group) control group. by gavage but this is
grown in the same the dried paper). The polyphenol together with 5 not described in the
field in Peru. hypocotyls. The content varied in the extracts. ovariectomised groups. method section. After
extract was spray- There were 5.81, Study period: 4 weeks the analysis of
dried. 1.76 and 6.5 g polyphenol (n=6). Groups: An intact variance, Scheffe’s test
and an ovariectomeised
(pyrogallol/100 g) spray-dried is used. This test
group received daily
extracted from the red, black compares all groups to
distilled water orally.
and yellow variants each other, including
Three ovariectomised
respectively. groups received daily the control group.
orally extracts of the
three types of coloured
roots corresponding to
4.3 mg
polyphenol/kg bw.

Black hypocotyls of Water. One gram Female mice (strain: Body weights. An increase in body weights After analysis of Rubio et al.
L. meyenii, grown of dried hypo- Kunming), three months (weight gain) was observed in all variance, differences (2011)
in Peru. cotyles yielded old, ovariectomised. groups after 35 days of dosing. were determined by
0.46 g of freeze- 500 and The greatest increases in Scheffe’s test.
dried hypocotyles. 2 000 mg/kg bw. Dosed weights (24.7 % and 22.3 % This test compares all
orally (by gavage) for 35 were observed in the groups to each other,
days, n=10. Three ovariectomised maca groups including the control
control groups: an receiving the lowest and highest group.
untreated group, an maca dose, respectively). The
ovariectomised group weight gain was 14.7 % in the
and an intact group intact, sham operated control
(sham operated) group and 16.7 % in the
ovariectomised control groups.

34
DTU The differences between dosed
and control groups were
statically significant.

Hypocotyls of L. An aqueous 6-month-old Body weight and Dosing with the aqueous The study is poorly Rubio et al.
meyenii. Red, extract was made ovariectomised female uterine weight. extracts of yellow, red and black described e.g. the (2006)
yellow and black from 500 g of mice (Swiss), n=20, variants of L. meyenii resulted in extract is poorly
variants , which are powdered were divided into a ↑ weights of the uterus (69.6 characterised. It is
not described hypocotyles, control group receiving mg, 60.8 mg and 72.7 mg unclear how the
further. which was cooked vehicle and three dosed respectively) compared to the authors calculates from
in 1500 ml of groups (1 g/kg bw per control group (35.51 mg). No the dose of extract to 1
water. The liquid day) dosed with the individual differences were seen g/kg bw maca per day.
After the analysis of
was cooled and different coloured between the weights of uterus
variance, differences
filtered. The variants (yellow, black in the three groups given L.
were determined with
filtrate was and red). Dosing period: meyenii. The body weights were Scheffe’s test. This test
freeze-dried. The 21 days. The mice had not affected by the maca compares all groups to
freeze-dried become ovariectome- dosing. each other, including
extract was nest when they were 3 the control group.
diluted. months old.
Roots (mixture of Gelatinisation Sexually mature female The following were No effect on body weights. In The numbes of animals Meissner et
yellow, black and process with rats (strain: Wistar) was measured in blood the intact rats: ↓ estradiol and in the different groups al. (2006b)
red colour types of water. ovariectomised and samples: TSH levels and ↑ progesterone are not indicated in the
L. meyenii) from divided into a control Hematological and level compared to the intact section about material
the Junin region of group that received biochemical control group. In and methods but
Peru. distilled water orally pameters (iron, ovariectomised rats there were described under the
(via gavage, n=12) and a triglycerides, total ↓ levels of estradiol, various tested
dosed group receiving a cholsterol, LDL progesterone, cortisol, and parameters. It is
total of 500 mg/kg bw and HDL. ACTH levels in the maca dosed unclear how many
dosed orally (by gavage, Hormones: rats compared with animals are in each
administered in two Estradiol, ovariectomised control. In the group, as the number
daily doses) for 28 days, progesterone, intact animals there were ↓ of samples analysed in
n=14. Two other groups cortisol, ACTH and granulocytes and ↓ iron in the the various tests varies.
were intact (sham- thyroid hormones maca dosed groups compared
operated), n=18, were (TSH, T3, T4). with the control group, while in
dosed in the same way the ovariectomised maca dosed
as the two animals erythrocytes ↓,
ovariectomised groups. haemoglobin↓, haematocrit ↓
and MCHC (mean corpuscular

35
DTU hemoglobin concentration) ↑
compared with the
ovariectomised control group.

36
DTU

Hypocotyls from Aqueous extract, All mice: strain Balb/c. Study 1: Body No effect on body weights in It is normal practice in Ruiz-Luna et
dried L. meyenii freeze-dried. All three studies weights, uterus study 1 and 2. Dosing with maca this type of experiment al. (2005)
(yellow) from the One gram of included control studied for implant resulted in an increased litter to weigh the pups but
company Santa freeze-dried groups that received ation sites and the size (Study 2). In litters of less it is not done in the
Natura Company, extract ~ distilled water orally embryos were than 7 pups there was an earlier experiment. The
Peru. 2.19 g of dried by gavage. Study 1: counted and vaginal opening, this effect was authors write that
hypocotyles. sexually mature, weighed. not seen in litters of more than 7 earlier vaginal opening
sexually Study 2: Body pups. The authors write that may be a possible sign
inexperienced female weights, duration according to the statistical of an estrogen effect.
mice, orally dosed (by of pregnancy, litter analysis, there was an effect on However, in their
gavage) with size at birth, the litter size after dosing with experiments, they think
1 000 mg/kg bw day for distribution of maca. Dosing with maca resulted that earlier vaginal
22-28 days (15 days gender, number of in higher uterus weights in opening is due to
before mating and first live pups after ovariectomised mice compared higher intake of energy.
7 days of pregnancy). birth, days 4 and to the control group. The weight of the pups
On dosing day 15 (n=11- 21 after birth, may have an impact on
12) each female mouse vaginal opening in the time of vaginal
was mated with a male females. Study 3: opening but the pups
mouse. The females Body weights, are not weighed. The
were killed on uterine weights in authors do not explain
pregnancy day 7. Study ovariectomised why a litter size of
2: Female mice and mice. seven pups is chosen as
same dose prior to the dividing line.
mating as in study 1,
but the mice were
dosed during the
gestation period and 21
days after birth (period
of breastfeeding).

37
DTU

Study 3: Female mice

(ovariectomised)
received orally
500 mg/kg bw per day
(by gavage) for
42 days, n=7.

Table 5: Human studies

Abbreviations used: ACHE acethylcholinesterase, ACTH adrenocorticotropic hormone, ALP alkaline phosphatase, ALT alanine aminotransferase, ASAT
aspartate aminotransferase, BMI Body Mass Index, CHOL cholesterol, CT cortisol, E2 17β estradiol, FSH follicle stimulating hormone, HDL high density
lipoprotein, IVF in vitro fertilisation, LDL low density lipoprotein, LH luteinising hormone, M one month with daily intake of 2 g Maca, MTCA (1R.3S)-1-
methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, P one month with daily intake of placebo, PG progesterone, SHBG sex hormone binding
globulin, SSRI: selective serotonin reuptake inhibitor, TRGL triglycerides, TSH thyrotropin, ULN Upper Limit of Normal.

Plant part Extract- Description of Dosages Endpoint(s) Outcome Comments Reference

tion Chemical study
identifica
tion
Dehydrated Gelatini- 12-week double- Tablets (‘Gelatinised The effect of No effect of maca on the Gonzales et al. (2003a)
root (Lepidium sation blind placebo Maca’, Maca Gelatini- maca on levels of measured hormones
meyenii). process controlled, zada La Molina, Lima). sex hormones 17- after 12 weeks of dosing.
with water. randomised, Maca 1 (n = 15) 1.5 g per alpha-
parallel study in day, divided into three hydroxyproge-
56 healthy men doses 8 hours apart. sterone,
(21- 56 years) Maca 2 (n=15) 3 g per testosterone, E2,
divided into six day divided into three FSH, LH and
groups. doses given with eight prolactin in
hours intervals. serum.

38
DTU
Plant part Extract- Description of Dosages Endpoint(s) Outcome Comments Reference
Chemical study
tion
identifica
tion
Maca 3 (n=15) 1.5 g per
day with one dose in the
morning. The last
11 subjects were divided
into three placebo
groups receiving placebo
with the same dosage
interval than the
intervention groups.

Maca (Lepdium Dried The Double blind 2 g maca per day (as Relief of Trial I: 8 women did not The plant part is Meissner et al. (2005)
conclude the study
peruvianum method placebo- gelatinised powder symptoms so only 12 out of 20 described as both root
Chacon syno- hypocotyls used for controlled clinical divided into 2 capsules in associated with women finished the and hypocotyl. There is
nym for L. chemical pilot study with the morning and 2 menopause intervention, apparently a considerable difference
meyenii) root. rehydrated Identificatio Caucasian post- capsules in the evening). assessed on the not associated with the between the length of
n is
before not menopausal Trial I: one month with basis of effects of maca. LH the dose of placebo and
exposure to described. women dosed for placebo followed by 2 hormonal- significantly increased the dose with maca in
after 3 months trial II.
short-term Content: 3 months (Study I, months with maca. Trial disorders (LH,
elevated Glucosi n = 20) or 9- II: one month with FSH, E2 and PG) Trial II: statistically
pressure in nolates as months (Study II, placebo after 8 months and a significantly lower FSH
of maca. questionnaire
moist synigrine n = 8). and higher E2, LH and PG
surroundin 200 mg/100 (P<0.05) after 9 months.
gs, followed g, Cam
by drying pestral
and 7.8 % of the
powdering.
unsaponifie
d
fraction,
Sigma-

39
DTU sterol 4.1 %
of the
unsaponifie
d
fraction, β-
sistosterol
24.2 % of
the
unsaponifie
d fraction.
L. meyenii, As As Double blind, 2 g maca per day (as Changes in sex Serum lipids only Meissner et al. (2006c)
Trial I: 14 women did
(maca) root described described randomised, gelatinised powder hormones (FSH, measured in Trial I. No
not conclude the study,
(black 16 %, under under placebo controlled divided with 2 capsules E2, PG, LH) and information of any
so only 88 women
yellow 48 %, Meissner et Meissner et multicenter study in the morning and 2 serum lipids adverse effects.
completed the study (P-
purple/red 9 % al. (2005). al. (2005). with 168 capsules in the evening). (CHOL, TRGL,
MM (n=55) and MM-P
and 27 % other Caucasian Trial I: two different HDL, LDL)
(n=33). Lower FSH
colours). postmenopausal combinations of one and symptoms of
(P<0.05) and higher E2
women dosed in 3 month with maca (M) discomfort
(P<0.001) after maca
months (Trial I, and one month with associated with
dosing compared to
n=102) or 4 placebo (P): P-MM menopause.
placebo in P-MM
months (Trial II, (n=62) and MM-P (n=40).
gruppen. Higher HDL
n=66). Trial II: six different-
(P<0.05) after maca
combinations (n=11) of
compared to placebo in
one month with maca
MM-P gruppen.
(M) and one month with
Trial II: Only 40 women
placebo (P): P-MM-P, PP-
completed the
MM, MM-PP, MM-P-M,
intervention. Therefore,
PPP-M and MMM-P.
only data
from P-MM-P, PP-MM,
MM-PP and MM-P-M for
statistical analysis. Lower
FSH (P<0.01) in the P-
MM-P group and higher
E2 (P=<0.05) and lower
LH (P=<0.05) compared
to placebo in the PP-MM
group. Reduction of
menopausal symptoms

40
DTU after maca compared to
the placebo group.

Maca (Lepdium As As Double blind, 2 g maca per day (as Measurements of Two women did not There seems to be an Meissner et al. (2006e)
peruvianum described described randomised, gelatinised powder E2, FSH, LH, PG, conclude the study so error with Figure 1 in
Chacon syno- under under crossover, pilot divided into 2 capsules
CT, ACTH, TSH, only 18 women finished the article. The
nym for L. Meissner et Meissner et study with 20 in the morning and 2 T3, T4 in blood the intervention. A headline is
meyenii) root. al. (2005). al. (2005). peri-menopausal capsules in the evening).
samples, blood higher level of FSH was “Menopausal Index by
(black 16 %, women (41-50 Intervention A: two pressure, body measured after two Kupperman”, but
yellow 48 %, years) dosed for months with placebo weights and months of dosing with according to the text it
purple/red four months. followed by two months
measurement of maca compared to was supposed to be the
9 %). of maca (PP-MM). the levels of Ca, placebo (P<0.01). Other results of the
Intervention B: opposite
K, Fe and lipid effects after maca dosing measurements of
order og intervention A
profiles in serum included reduction of hormones. The results
(MM-PP). and relief of body weight, lower for the hormones are
menopausal systolic and diastolic therefore cited only
symptoms. blood pressure, increase from the text.
in levels of E2, PG, HDL
and iron in serum
(P<0.05). Reduction of
menopausal symptoms
after maca dosing
compared to the placebo
group.
L. meyenii As As Double blind 2 g maca per day (as Body weights and Reduction of BMI, LH, T3, Crossover study (PP- Meissner et al. (2006d)
(maca), root described in described in randomised gelatinised powder height, FSH, E2, cortisol and ACTH after MM and MM-PP) is
(black 16 %, Meissner et Meissner et crossover study divided by 2 capsules in PG, LH, CT, ACTH, dosing wit maca identical to the
yellow 48 %, al. (2005). al. (2005). with 34 Caucasian the morning and 2 TSH, T3, T4, compared to placebo research previously
purple/red post-menopausal capsules in the evening). TRGL, CHOL, HDL, (P<0.05). described in Meissner et
9 %). women dosed for Two group with 11 LDL and bone Increased E2, LDL, iron al. (2006c)
four months. women in a crossover density. and calcium after maca
design: PP-MM and MM- Symptoms dosing compared to the
PP. In addition, two associated with placebo group (P<0.05).
groups of 6 women given menopause. Reduction in symptoms
maca or placebo for four associated with
months (MMMM and menopause after maca
PPPP, respectively). dosing compared to
placebo.

41
DTU
Dried maca Randomised, Dried maca powder. The effect of No significant effects on No side effects Brooks et al. (2008)
powder (Maca double-blind Each woman received in maca on hormone profile. mentioned.
Power, Incan placebo any order 3.5 g of dried hormone profile Statistically significant
Food, controlled maca pulver per day for (in blood serum) reduction in symptoms
Murwillumbah, crossover study in 6 weeks and placebo for of E2, FSH, LH associated with
NSW, Australia) 14 postmenopau- 6 weeks. and SHBG) and menopause. The power
not specified. sal women aged symptoms of the study is too small
53.5 ± 10.8 years. associated with toshow statistically
menopause. significant changes below
30 %. Increase in E2.

42
DTU
Plant part Extracti Description of Dosages Endpoint(s) Outcome Comments Reference
Chemical study
on
identifica
tion
L. meyenii Double blind, 1.5 g maca per day and Sexual Possible beneficial effect There was no placebo Dording et al. (2008)
(maca) root. randomised, 3 g per day. Purchased dysfunction on SSRI induced sexual group - all patients
parallel, pilot from ‘A Healthy studied dysfunction. received maca. Eleven
study with 20 with a out of 16 patients
Alternative
depressed questionna reported at least one
patients (17 (ahealthya.com) in Long ire side effect during the
women, 3 men), Island’. study. It is not apparent
36 ± 13 years of at which dose level
age with drug- adverse reactions was
induced (SSRI- reported. Side effects
induced) sexual included:
dysfunction. gastrointestinal
disturbances (n = 5),
headache (n = 2),
irritability (n = 2),
anxiety (n = 1),
increased urination (n =
1), blurred vision (n =
1), sleep disturbance (n
= 1), increased sweat
production (n = 1),
increased dream
activity (n = 1), thicker
discharge at menstrua
tion (n = 1), and
deterioration of
fibromyalgia (n = 1). All
side effects were
transient and no
patient left the study
due to side effects.

43
DTU
Plant part Extracti Description of Dosages Endpoint(s) Outcome Comments Reference
Chemical study
on
identifica
tion
Maca hypocotyl. Extraktion Determined Randomised, The 101 patients were BMI, blood Statistically significant Two patients dropped Valentova et al. (2008)
with with GC- placebo con- divided into five groups pressure, plasma trend for increased out of group 3.
methanol MS: β- trolled 90-day of which group 3 lipids (cholesterol diastolic blood pressure Apparently not
and Sitosterol study in 101 consisting of 11 women and compared with placebo associated with the
chloroform (9.32 mg/g) patients with and 8 men (46.6 triglycerides), (P = 0.027). Statistically effectes of maca.
(1:1). , 3-hydroxy- metabolic ± 8.7 years) received lipoprotein lipi- significant increase in
5-ergosten syndrome (58 0.6 g maca per day. The ds, glucose, Mg, ASAT levels compared
(0.75 mg/g) women and 43 remaining four groups C-reactive to placebo (P = 0.045).
and 3,5- men). received silymarin, protein, uric acid,
stigmasta- silymarin + yacon, urea, creatine,
diene silymarin + maca or ALT and ASAT.
(0.32 mg/g) placebo (19 women and
. 15 men (50.9 ± 12.8
years of age)).

L. meyenii Reported adverse A teaspoon of maca Intermenstrual The prolonged intermen- Srikugan et al. (2011)
(Maca) reaction in a powder dissolved in milk hemorrhage and strual bleeding is
woman in her 30s per day. The duration of increased probably due to the
referred to further intake is not reported. testosterone intake of maca.
investigaton due level. Symptoms showed up a
to increased few weeks after the
testosterone level women began eating the
and prolonged maca powder and was
intermenstrual declining a month after
haemorrhage . the intake had stopped.
The authors conclude
that the excessive
testosterone levels are
due to assay-in
terference due to testo
sterone-like maca

44
DTU
Plant part Extracti Description of Dosages Endpoint(s) Outcome Comments Reference
Chemical study
on
identifica
tion
constituents and not
endogenously increased
testosterone.
L. meyenii Manic Quandt & Puga (2016)
Abstract from a
(Maca). episodes in
conference. It is
an individual
therefore not possible to
after intake of
use the data in the risk
maca
assessment.
Lepidium Adverse reactions 300 ml of Maca medici Liver injury. Maca induced liver- *R = Xiao et al. (2017)
meyenii (Maca). in a 30-year-old nal liquor with 50 % damage based on an R* (ALT/ULN**)/(ALP/ULN
man with (V/V) alcohol. value of 40, augmented ). A R-value > 5
abdominal ALT, ASAT and total suggestive of a
distension, bilirubin levels. The hepatocellular drug
anepithymia, sour authors conclude that induced liver injury
regurgitation, and the liver injury was not (Weiler et al. 2015).
eructation after related to acutely alcohol **ULN (the upper limit
ingestion of 300 induced liver injury. of normal values)
ml Maca medi
cinal liquor with
50 % (V/V) alcohol
10 days earlier.
These symptoms
were followed by
jaundice for one
week.

Lepidium Review. Review of Brief description of the Beharry & Heinrich (2018)
meyenii (Maca). reproduction toxicity of maca.
problems. According to the authors
no adverse reactions
have been reported in
clinical trials. The two
case studies of Srikugan

45
DTU
et al. 2011 and Quandt &
Puga (2016) are
mentioned. The authors
conclude that years of
intake of maca among
people living in the
Andes indicate that
maca is safe to eat.
Maca root. Prospective Maca ingested together Effects of food Lower number of Correlation between Kieu et al. (2019)
cohorte study with other supplements supplements on fertilized eggs in users of maca intake and effects
with 25 IVF in a total of five patients. oocytes, embryos the food supplements in IVF patients has not
patients of which Doses are not reported. and number of concerned (P = 0.046) been demonstrated.
13 used dietary successful
supplements. pregnancies efter
IVF.
Lepidium Review. Doses from 500 to Review of Likelihood score E = NIH (2019)
meyenii (Maca). 3000 mg per day. possible liver unlikely cause of clinical
injury caused by apparent liver injury.
maca. The publication
mentions that side
effects are rare and mild
and mainly includes
gastrointestinal
symptoms and
headache.

46
 DTU

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