As a fresh root, maca contains more than 80% water [
17]. Peruvians commonly drink it as a juice at home and when compared against non-consumers of maca, experience several health benefits, including higher levels of estradiol and testosterone, lower systolic blood pressure, and serum levels of interleukin-6 (IL-6), as well as an improvement in chronic mountain sickness and better performance on a lower-limb strength test [
97]. Indeed, these benefits would seem to come from consistent consumption in the daily diet over years, if not decades, when considering that published clinical research over short periods (weeks or even months) from raw, gelatinized, or even extracts of maca have not demonstrated statistically significant efforts on hormones. There can be variability in maca’s nutrient levels depending on several factors: the location grown [
7,
72], its size and weight [
67], the part of maca tested [
60], and postharvest conditions involving drying, storage, and maceration [
83]. Maca’s macronutrient composition as a dehydrated powder includes carbohydrates (55–73%, mostly starch), fiber (8.2–25.6%), protein (8.9–21%), and fat (0.6–2.2%) [
7,
10,
17]. Amino acids identified in various parts of maca include aspartic acid, glutamic acid, serine, glycine, cysteine, alanine, arginine, tyrosine, hydroxyproline, proline, histidine, threonine, phenylalanine, D-phenylalanine, valine, methionine, isoleucine, leucine, lysine, and tryptophan [
60].
Researchers at Jinzhou Medical University have suggested that essential oils, lipids, and polysaccharides are the biologically active constituents in
L. meyenii and may contribute to its antioxidant activity, with the essential oils being the most potent contributor to free-radical scavenging action [
9]. There may be more complexity to the constituents of maca. Carvalho and Ribeiro [
19] reported on 101 bioactive phytochemicals in
L. meyenii extracts. These structurally diverse secondary metabolite compounds encompass a wide range of secondary phytometabolites such as glucosinolates, isothiocyanates, flavonols, phytosterols, polysaccharides, fatty acid derivatives (2-oxononadecanoic acid, anandamide, oleamide), and alkaloids such as macaenes, macamides, and thiohydantoins [
19,
101]. Meissner et al. list seven categories of phytochemicals within
L. peruvianum with known physiological relevance: amides, carbolines, catechins, cyanogenic compounds, fatty acids, glucosinolates, and imidazole alkaloids [
72].
Another study indicated that red maca had higher protein and potassium content but less soluble reducing sugars, riboflavin, and iron than black maca [
9]. Analytical attempts have been made to evaluate the phytochemical content of the different colorful varieties of
L. meyenii [
9,
71] and
L. peruvianum [
39,
67,
72,
103]. Seven compounds were reliably detected in yellow, black, white, and purple maca (
L. meyenii) samples grown in China:
p-hydroxybenzylglucosinolate, benzylglucosinolate,
N-benzyl-9Z,12Z,15Z-octadecatrienamide,
N-benzyl-9Z,12Z-octadecadienamide,
N-(3-methoxybenzyl)-hexadecanamide,
N-benzyl-hexadecanamide, and
N-benzyl-9Z-octadecenamide [
71]. Of these samples tested, yellow and black maca were highest in glucosinolates (1.55%), followed by white (0.93%) and purple (0.76%) maca [
71]. Macamides were lowest in black maca (0.15%) compared with the other colors (0.23–0.29%) [
71].
4. Clinical Application: Endocrine System Support
The rationale for this focus is that this area is where its central claims for use (e.g., energy, fertility, menopausal symptoms, prostate health, reproductive function) reside from a mechanistic point of view and where there exists most of the research, relative to its effects on other parts of the body.
4.1. Adrenal Health
In botanical medicine, maca is classified as an adaptogen [
3,
145]. Adaptogenic herbs are unique from other substances in their ability to modulate hormones and the immune system, assisting with maintaining optimal homeostasis. Adaptogens have a modulating effect on the body and can either tone down the activity of hyper-functioning systems or strengthen the activity of hypo-functioning systems [
150]. While the primary proposed mechanism of action for adaptogens is the impact on the hypothalamic–pituitary–adrenal [
151] axis, especially cortisol output, they can also display anti-inflammatory and antioxidant effects and influence gene regulation involved in modulating pathways of detoxification and stress regulation [
150].
Indeed, maca’s function would fit the definition of an adaptogen; however, as discussed herein, could maca be in a category by itself? It may be separate from being solely classified as an adaptogen due to the various phenotypes having different physiological effects and modulating other systems beyond the adrenal glands. The research utilizing standardized, quality-controlled maca formulations indicates that the entire endocrine axis, consisting of the hypothalamus, pituitary gland, thyroid gland, adrenal gland, and gonads (HPTAG axis), is impacted.
4.2. Ovarian Health
Scientific research suggests that when combining the purported benefits of select colors, maca’s mechanisms surpass that of a classically defined adaptogen [
27]. Importantly, research conducted more than fifty years ago by Dr. Gloria Chacón de Popovici [
152] touted that alkaloids in maca were stimulating the testes and ovaries of rats, extending its beneficial effects past the hypothalamus–pituitary–adrenal [
151] axis into the hypothalamus–pituitary–adrenal–gonad (HPAG) axis [
27]. However, to date, only one select formulation of specific concentrated maca phenotypes (referred to in research as Maca-GO
®, commercially as Femmenessence
®) has exhibited modulation of the hypothalamic–pituitary–ovarian (HPO) axis in early postmenopausal women via clinical changes in estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) [
24,
25,
26,
27].
Conversely, in another clinical trial, postmenopausal Chinese women from Hong Kong taking 3.3 g daily of an unspecified color of maca known commercially as Maca Power (Healthychoices, Murwillumbah, NSW, Australia) for six weeks did not experience any changes in E2, FSH, or LH, compared with six weeks on a placebo [
153]. It was not stated in this study whether the maca used was raw or gelatinized. Similar to these latter findings, the researchers found no differences in these hormones in fourteen postmenopausal women taking 3.5 g of Maca Power (Incan Food, Murwillumbah, NSW, Australia) daily for six weeks with a six-week crossover on placebo. There were no significant differences in serum concentrations of these hormones (E2, FSH, LH), even though symptoms on the Greene Climacteric Scale, such as anxiety, depression, and sexual dysfunction, were improved using Maca Power [
154]. A study in healthy, perimenopausal Japanese women given a maca extract standardized to at least 1.2% benzyl glucosinolate, known as Maca-BG1.2
TM (CPX PERU S.A.C., not currently sold commercially), for eight weeks found a 2.2-fold increase in E2 levels, although this was not statistically significant [
155]. These findings, in conjunction with the Maca-GO
® results, highlight how important phenotype and concentration are in eliciting statistically significant effects on hormones in peri- and post-menopausal women.
Concerning menopausal symptoms, one of the studies using Maca Power mentioned above reported non-significant menopausal symptom reduction compared with a placebo (using Greene’s Climacteric Scale, the total score after six weeks of maca supplementation was 17.6 ± 10.0,
p = 0.07, and the placebo group was 16.8 ± 9.1,
p < 0.05) [
153]. Alternatively, the clinical trials using Maca-GO
® reported highly significant reductions in menopausal symptoms in early postmenopausal women, notably hot flushes and night sweats, and overall symptoms, including nervousness, depression, sleep, and heart palpitations, using Kupperman’s Menopausal Index and Greene’s Menopausal Score (
p < 0.001) [
24,
25,
26]. These results further validate how important phenotype and concentration are for ensuring optimal clinical outcomes.
Eighty-five percent of peri- and postmenopausal women experience various menopausal symptoms, including hot flushes, night sweats, sleep disturbances, mood imbalances, loss of libido, weight gain, and vaginal dryness, that can last for decades [
156,
157]. Apart from debilitating symptoms impacting the quality of life, the significant loss of hormones experienced at these stages of life results in substantial increases in morbidity and life-threatening conditions, ranging from osteoporosis to cardiovascular disease [
158]. These serious health implications have naturally given rise to the use of HRT and bioidentical hormone therapies (BHRT). While the introduction of exogenous hormones is a logical solution, the fluctuations of hormones experienced during perimenopause and the simultaneous increase or proportional increase, such as between E2 and testosterone (T), indicates that a potentially more optimal functional medicine approach would be to support the declining function of the endocrine (hypothalamus–pituitary–thyroid–adrenal–ovarian, HPTAO) axis, thereby creating hormonal “balance”.
With this novel mechanism of action of supporting the endocrine axis and regulating the endogenous production of hormones despite the absence of the introduction of exogenous hormones, it would seem that this would be an ideal first step as a treatment for many women. From that point forward, a clinician could assess if there is a need for additional exogenous hormone support and, if so, which hormones and to what degree, aligning with the current North American Menopausal Society (NAMS), Endocrine Society, and National Health Service (NHS) recommendations of personalizing the dose (often the lowest) and the duration of HRT (often the shortest) to the individual patient to maximize benefits and minimize risks [
159,
160,
161]. Furthermore, this strategy offers an alternative for women who are over ten years beyond their menopausal transition, where there are heightened concerns about starting hormone therapy at an advanced age. It may also be a helpful, more natural approach for women who are looking for long-term hormone support throughout their life without side effects or risk or women for whom hormone therapy may not be an option or desired for various reasons (77% of women surveyed in one study were reluctant to do hormone therapy despite having symptoms) [
162].
Apart from identifying phenotype (color), another point to consider is dose and concentration. Both Maca-GO® and Maca-BG1.2TM were noted as a concentration and an extract, respectively, versus Maca Power, which was undefined. Daily doses used in the abovementioned studies ranged between 300 mg and >3000 mg. Still, they did not define active ingredient parameters, except for Maca-GO®, which had glucosinolates as one of its standardized biomarkers and more information on sourcing described in the study methods (country, elevation, hypocotyl size, and manufacturing procedures). This additional information would enable greater accuracy in assessing and differentiating maca ingredients. Moreover, the genetic and/or cultural aspects of study participants could relate to the menopausal transition in a way that would result in maca products having differential effects.
In a published case report of a Caucasian female in her thirties taking a maca extract to improve energy and libido, there was evidence of increased plasma testosterone; however, no symptoms related to virilization [
163]. Upon further investigation, the researchers noted that there was analytical inference in the immunoassay caused by maca supplementation [
163]. Therefore, it is worth noting from a laboratory test point of view that there can be potential interference in the testosterone immunoassay in women taking a maca supplement. However, this is a single subject, and these results have not been reported elsewhere.
Of note, maca is also not a phytoestrogen with high concentrations of isoflavones like soybean and red clover [
27,
135,
152], but it has been proposed to have progestin-like activity due to increases in uterine weight seen in a study with ovariectomized mice [
164]. While it may not be a classical phytoestrogen, by nature of its potential ability to enhance endogenous E2 and P levels depending on the possible phenotypes used and the form it is in, its use would be contraindicated in those with a personal history of hormone-sensitive cancer. However, with several chemopreventative compounds present in some forms and phenotypes of maca, there will no doubt be additional investigation on this topic in future research [
95].
4.3. Testicular and Prostate Health
Standardized formulations known as MacaPure M-01 and MacaPure M-02 derived from unspecified colors of maca
(L. meyenii) root were shown to enhance sexual function in mice and rats, suggesting possible regulatory modulation of gonads through specific phytochemicals like macaenes, macamides, and certain unsaturated fatty acids and their amides [
126]. It is of interest to note that increased libido in men due to taking maca may not be due to hormone changes. In a clinical study, men aged 21–56 years old were given two doses of gelatinized dehydrated maca root or placebo for twelve weeks. While sexual desire increased at eight and twelve weeks, the effect was not attributed to changes in serum T or E2 [
50]. In another study in men of the same age range, there was no statistically significant difference in T, FSH, LH, prolactin, or E2 in men when given gelatinized maca root (no colors specified) or placebo in doses known to be used for aphrodisiac enhancement [
165].
Men with mild asthenozoospermia and/or mild oligozoospermia given a non-specified color of maca (2 g/day) or placebo for 12 weeks presented statistically significant changes in sperm concentration [
166]. However, the effects on sperm with this maca product are rather specific, considering the researchers found no significant differences in other parameters (sperm volume, mobility, and morphology) between the maca-supplemented and placebo groups [
166]. Conversely, other studies using black maca in animal models have shown an improvement in parameters related to sperm, which may suggest that the color of maca may be relevant to men’s health [
29,
32,
33,
34,
167,
168]. A dried maca extract (of unspecified color) supplement given to non-Peruvian men for twelve weeks resulted in greater improvements in erectile dysfunction and well-being compared with those given a placebo [
169].
Another important mechanism related to the endocrine system is its anti-inflammatory effect in the prostate gland through red maca’s impact on decreasing prostate weight (
Figure 3) [
51]. While the preponderance of data on prostate health advocates the use of red maca, there may be other colors of maca or combinations of maca that would also benefit specific physiological effects related to the function of this gland.
Figure 3. Endocrine system modulation by maca phenotypes.
4.4. Thyroid Health
Subsequent clinical studies on Maca-GO
® also revealed some degree of positive impact on the thyroid hormone, triiodothyronine (T3), further suggesting that the hypothalamus–pituitary–thyroid–adrenal–gonad (HPTAG) axis may be affected through specific phenotypes and concentrations of maca, though this topic is less studied (
Figure 3) [
26,
27].