This study was primarily designed to determine the efficacy of oral consumption of extracts of black maca or red maca, a cruciferous plant, during a 12-week period in a double-blind placebo-controlled trial at LA and HA. Secondary objectives of the study were the determination of acceptability, adverse effects, and effect of altitude on outcomes after maca intervention.
3.1. Primary Outcomes: Efficacy
During the period of the study, consumption of spray-dried extracts of black and red maca increased self-perception of sexual desire, mood, and energy. This is in accordance with experimental studies and results in human beings with unidentified maca [8
This trial was also able to demonstrate that spray-dried extracts of black maca and red maca have different biological properties. In fact, self-perception of increase of sexual desire, mood, and energy, and reduction in CMS score were more relevant with red maca than with black maca. This is in accordance with different properties shown for black maca and red maca in experimental designs [8
]. Black maca demonstrated better response with hemoglobin levels at high altitude. Both maca phenotypes have similar responses in HRQL score.
Although red maca increased sexual desire more than black maca, the effect seems to be modest since it represented only 50% of the subjects. Moreover, a placebo effect was observed particularly at HA. In a previous study using gelatinized maca in men at LA, sexual desire increased only in 42% and after eight weeks of treatment [16
]. Maca dry extract supplementation was also useful to improve subjective perception of general and sexual well-being in adult men with mild erectile dysfunction [17
]. Another study using maca flour at a dose of 3.3 g/day for six weeks was unable to show an increase in sexual desire in post-menopausal women [15
]. Stone et al. [14
] showed an increase in sexual desire at week 4 using an extract of unidentified maca. Although extract of maca, particularly the red phenotype, seems to be better than flour or gelatinized maca, the results are still modest.
Maca shows greater effects on mood and energy. In fact, over 80% of the population reported increased mood and energy following maca consumption.
Among the most notorious compounds in maca are macamides, a group of fatty acid lipids. These compounds seem to act on a widely expressed signaling system known as the endocannabinoid system (ECB) [18
]. Macamides inhibit anandamide degradation through the inhibition of fatty acid amide hydrolase (FAAH). Anandamide acts on the CB1 receptor. Maca’s effects on mood might be linked to its role on the CB1 receptor since other FAAH inhibitors have been shown to act as antidepressants by enhancing central serotonergic and noradrenergic transmission and promoting neurogenesis in the hippocampus [20
The presence of GABA might also explain the elevated mood [21
] after the 12 weeks of treatment. GABA was higher in red than in black maca and this may explain the differences in the response on mood. Indeed, the present study showed that treatment with red maca was more effective at increasing mood than black maca.
Choline is another compound present in spray-dried extracts of maca. Choline supplementation improves neurocognitive functioning [22
]. Choline also plays a critical role in hepatic function and systemic lipid metabolism [25
]. Mood is also improved after choline supplementation [26
Choline acts in the brain as an agonist of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) [27
]. Choline is also antinociceptive [27
] and this property may improve the score in the HRQL questionnaire. The generic health-related quality of life (HRQL) questionnaire used for assessment health status [12
] showed that the score increased with treatment with spray-dried extract of black or red maca compared to the placebo. This was an effect of maca and not a placebo effect. This finding confirms previous findings that populations consuming maca at HA have better HRQL scores than populations not consuming maca at the same altitude [8
Our finding of increased HRQL scores after maca consumption is also in concordance with the absence of serious or severe adverse effects due to consumption of spray-dried extracts of red or black maca reported in the present study.
In the present study, at LA or at HA, systolic or diastolic blood pressure did not change after consumption of spray-dried extracts of red or black maca compared to the placebo. In a previous study in postmenopausal Hong Kong Chinese women, there was a significant reduction in diastolic blood pressure over 12 weeks of treatment with 3.3 g/day of maca [15
]. However, there is a report in patients with metabolic syndrome indicating that maca administration at a dose of 0.6 g/day for 90 days resulted in a moderate elevation of AST and diastolic blood pressure [28
]. There is no other study confirming this finding. In fact, in a previous study, no increase in arterial blood pressure occurred in healthy men who took gelatinized maca at doses of 1.5 of 3.0 g/day for 90 days [1
]. The fact that maca contains high amounts of potassium and low of sodium [1
] and inhibitory activity of ACE [7
] suggests that it is feasible that maca may reduce arterial blood pressure rather than increase it.
Spray-dried extract of black maca reduced fasting glucose levels over time whereas in the placebo group they did not change during the treatment period of 12 weeks at LA and at weeks 4 and 8 at HA. This result corroborates previous results from experimental studies in which black maca reduced fasting blood glucose levels in mice with streptozotocin-induced diabetes [5
]. In addition, maca, as well as rosiglitazone, significantly improved glucose tolerance, decreased the AUC (area under the curve) of glucose, and reduced glycemia [29
]. In our study, black maca reduced glycemia at both LA and HA. A placebo effect also occurred for glycemia reduction over time: glycemia was significantly lower at HA than at LA, confirming results previously reported [30
Hemoglobin was another primary outcome assessed, since scientific publications without scientific evidence suggest maca has been used for centuries in the Andes to treat anemia [15
]. This assumption is probably due to the presence of iron in maca [1
]. However, our results at LA show that 12 weeks of treatment with spray-dried extract of black or red maca has no improving effect on hemoglobin level, suggesting that maca is not useful in treating anemia at LA.
On the contrary, our results indicating a reduction in hemoglobin levels at HA after black maca consumption are remarkable since high hemoglobin levels at HA are associated with chronic mountain sickness, a condition of lack of adaptation to HA compromising almost 20% of the population living over 4000 m [11
]. Previously, a cross-sectional study in a population close to Cerro de Pasco (over 4000 m) showed that maca consumers have lower CMS scores than those non-maca consumers living in the same place [8
]. Data suggest that red maca could be acting on signs and symptoms whereas black maca is acting on high hemoglobin levels. Our results suggest that this is an effect based on maca. The consumption of maca, particularly the red phenotype, could be an important alternative in cases of CMS.
Our study shows a placebo effect in several variables studied, although these were not consistent over time. This placebo effect was also observed in other studies with maca [15
], but our results are consistent, in which several of the primary outcomes studied were different with maca than with the placebo.
Our results are in accordance with other authors who suggest that the placebo effect should be part of alternative medicine [32
Recent findings showed that neurotransmitter pathways might mediate placebo effects [33
]. The higher placebo effect observed at HA than at LA is remarkable. Genetic signatures have been identified in those subjects responding to placebo [34
] and this may explain the differences between populations at LA and HA. At HA, placebo administration to headache sufferers inhibited the nocebo-related component of pain and prostaglandin synthesis [35
]. This may explain the reduction of CMS score with placebo in headache as part of the symptoms included in the CMS test.
3.2. Secondary Outcomes: Acceptability
Most of the subjects included in the present study were satisfied with the taste of the product consumed independently if they consumed a placebo or a spray-dried extract of maca. This high satisfaction occurred as early as the first week of treatment and reached its highest values at weeks 8 and 12.
This is an important finding since cruciferous vegetables are bitter, which might be off-putting to consumers [36
]. Thus, high acceptability of consuming a spray-dried extract of maca, another cruciferous vegetable, might be important to promote its consumption as a value-added product. Perceived bitterness of cruciferous vegetables varies from person to person, which suggests a genetic contribution in acceptability [37
]. Glucosinolates and metabolites, compounds present in maca (Table 1
), impart the characteristic bitter taste and pungent odor of cruciferous vegetables [38
]. Maca flour has a pungent smell and bitter taste and may result in aversion in persons not accustomed to its consumption.
Our results showed differences in acceptability between populations at LA and at HA. It is possible to think that subjects at LA are not as accustomed to the maca flavor as those living at HA. Our study used spray-dried extracts of black maca or red maca instead of flour, resulting in an improvement of the taste with maintenance of biological activity.
3.3. Adverse Effects
It is common to find severe adverse effects with medicinal plants’ usage [40
]. For such reason, since interest in maca, a nutraceutical plant, has increased worldwide, it is important to know its adverse effects, particularly in populations with little or no experience with its consumption.
Another secondary outcome of this study was to determine the adverse effects after consumption of spray-dried extracts of maca and compare data with those obtained after placebo consumption during an intervention period of 12 weeks. There were no severe or serious adverse effects due to consumption of an extract of red or black maca, and no subject discontinued the trial due to an adverse effect. The discontinuation rate was similar in the three groups of treatment at LA and at HA. Most occurred at the first month due to reasons besides adverse effects or disagreement with the products. Moreover, the percentage of people missing the follow-up was similar between groups consuming the placebo, black maca extract, or red maca extract.
Previous findings in experimental animals receiving different phenotypes of maca (black, red, or yellow) showed no acute toxicity at ≤17 g of dried hypocotyls/kg body weight (BW) [1
]. Similarly, rats treated chronically for 84 days with 1 g maca/Kg BW showed no adverse side effects and a histological picture of the liver similar to that observed in controls [41
]. Gelatinized maca given for 12 weeks to healthy adult men and women also showed that consumption was safe [13
]. All data taken together suggest that in humans the consumption of spray-dried extract of red or black maca at the dose used in the present study seems to be safe. This dose is used in Peru in self-care and/or medical practice.
The use of 3 g of the spray-dried extract was calculated from data obtained in experimental animals using the body surface normalization method [42
The present study provides data that could be the basis for the use of extracts of black or red maca (Lepidium meyenii) in adult human subjects in possible clinical therapies.