Maca

'Maca' is the common word to refer to the plant Lepidium Meyenii, of the genus Lepimedium and the famile of Brassicaceae; this family is that which also holds cruciferous vegetables such as broccoli, cauliflower, collard greens, and mustard. The plants most closely related to Maca (taxonomically) are rapeseed, mustard, turnip, black mustard, cabbage, garden cress, and water cress.^[1] Maca has been traditionally used as a folk medicine for vitality and fertility in the Andean region of Peru and has been used in both genders as well as animals,^[1][2] and is sometimes referred to as Peruvian Ginseng despite not bearing any resemblance to the Panax Ginseng plant of its family.^[1] It is grown exclusively in the Andean Region of Peru at a height level of 4000-4500m above sea level^[3] as its growing conditions require winds, cold, and ample sunlight^[1] and possibly being more conducive to growth, as one study noted growth rates were faster with lower temperatures.^[4] Interestingly it appears Maca may reverse the decrease in spermatogenesis that occurs at this height range (in rats).^[5]

Maca is grown exclusively in one height region of Peru, where it is historically used as a fertility enhancing agent. It belongs to a similar plant family as Broccoli and other Brassica vegetables

When used as a food product, the bulbous hypocotyls (stem-like protuberances) are dried and then eaten to levels upwards of 20g daily with no reported side-effects associated with this method, and when dried hypocotyls can be stored for years.^[1] Maca is frequently boiled and drunk as a juice, due to the storage form of dried hypocotyls being too hard to bite. Modern usage of maca tends to be capsules.

Nutritionally, Dried Maca (vegetable, not supplement) is:^[1][3]

• 10.4% water content unless otherwise dehydrated^[3]
• 10.2-16% protein by weight, with a small sarcosine content (0.70mg/100g)
• 59% carbohydrate
• 2.2% lipid (of which 40.1% are saturated and 52.7% unsaturated)
• 8.5% fibers
• Minerals are calcium (150mg/100g), copper (5.9mg/100g), zinc (3.8mg/100g), and potassium (2050mg/100g) and the overall Ash content is 4.6%^[3]
• Vitamins such as Vitamin C (8mg/100g), Riboflavin (650mcg/100g), and Thiamine (280mcg/100g)^[3]
• Phenolic compounds (at around 5.5-7.6mg/g, poor content)^[6]
• 53 Essential Oils (aromas) with most being Phenyl acetonitrile at 85.9%^[7]

Maca tends to have its hypocotyls (protuberances that resemble turnips) as the part of the plant commonly eaten, and in this form it is mostly carbohydrates and fibers with a hard texture

There are over 13 different variants of Maca known (all being referred to as Lepidium meyenii) which are produced differently depending on cultivar, ranging from White to Black; the most common is Yellow consisting of 47.8% and is the most commercially desirable.^[8] These variants are named due to the coloration of the hypocotyls being visibly different.^[1] These variants are sometimes referred to as ecotypes of Maca.^[9]

In comparative studies, Black Maca appears to be more neuroprotective than Yellow or Red^[8] and produce the greatest benefit on spermatogenesis.^[10] Red Maca, but not Black or Yellow, may reduce prostate size.^[11]

Different 'variants' of Maca based on the color of the hypotocyl, they are similar for the most part but on some properties they may be more specialized.

The noncaloric bioactives found in Maca tend to be:

• Macaridine^[12] and Maca alkaloids that are exclusive to Maca^[1]
• Macaenes which are Maca-exclusive unsaturated fatty acids^[13][14] and include
• Macamides, which are amine derivatives of the Macaenes;^[15] some include n-benzylhexadecanamide and n-benzyloctadecanamide^[15] and range from 0.0016 to 0.0123% dry weight (low content)^[15]
• Lepidine A and B,^[16] two imidazole alkaloids with the names 1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimidazolium chloride; respectively
• Glucosinolates such as glucoalyssin (0.6-0.9% total glucosinolates^[9]), glucosinalbin (0.02-0.028% total glucosinolates^[9]), glucobrassicanapin, glucobrassicin, glucoaubrietin (aka. glucolimnathin; 6-6.2% total glucosinolates), 4-methoxyglucobrassicin, glucotropaeolin (80-90% total glucosinolates^[17][9]),^[9][1] and Benzyl glucosinolate (7.01-17.5mg/100g dry weight of Red Maca)^[18] with aromatic glucosinolates consisting of up to 99% of total glucosinolates by weight with no significant differences between ecotypes.^[17][9]
• 7 alkamides^[14]
• Methyltetrahydro-β-Carboline molecules such as MTCA^[19] in the butanolic fraction^[20]
• Beta-Sitosterol^[12]

The alkaloid known as macaridine is said to be the main bioactive, as well as some glucosinolate content; the macaene fatty acids are unique to Maca, but their content as well as the amount of their derivatives in Maca (the macamides) may be too low to be the main bioactives

In reality, the active components and what they do in Maca are not too well known; mostly estimations

Gelatinized maca refers to a process known as starch gelatinization where maca powder is heated in water forming a collection of polymers in solution,^[21] and is claimed to increase the digestability and bioavailability of maca supplements when compared to the raw powder.

There are currently no studies assessing how this process affects the activity of maca, which is relevant since glucosinolates are known to be heat sensitive while the immune effects of maca may be traced back to the carbohydrate content (bioactive carbohydrates underlying many benefits seen with supplements and immunity, such as ganoderma lucidum and astragalus membranaceus).

A popular form of maca that is not studied, and it is unknown how this process affects the activity of the supplement. Claims related to the digestability of maca in this form relative to the raw powder are also not assessed.

Mechanistically, one study investigating whether there was a correlation between hormones and aphrodisia failed to find any relation and failed to find any spike of hormones in the study population despite aphrodisia being present; this study suggested that the mechanisms of Maca on aphrodisia are not mediated by hormones.^[22] These aphrodisiac effects also appear to be independent of the ability of Maca to induce locomotor activity, where in a study on rats finding benefits to mounting and intromission latency and the intercopulatory interval (not dose dependent) as well as post-ejaculatory latency (dose-dependent up to 75mg/kg) there was no apparent correlation with the observed increase in locomotion.^[23]

The active components may be the macamide (lipid) component due to a lipid extract being bioactive.^[13]

Mechanisms are independent of any hormones usually involved in aphrodisia (testosterone, estrogen, luteinizing hormone, etc.) and of other neural effects of Maca

One rat study published comparing acute effects of Maca against chronic dosing noted that, after consumption of 25 or 100mg/kg aqueous extract in mice, that a single dose 30 minute before sexual activity failed to increase mounting or ejaculatory parameters in mice.^[24] Measurements after a week started to trend towards significant improvements, but at a week and after 21 days these differences failed to be statistically significant.^[24]

Maca root appears to exert aphrodisia in a 'build-up' manner, with more efficacy coming from repeated doses and independent of timing around sexual activity

In otherwise healthy men taking 1.5g or 3g Maca daily, Aphrodisia (by self-report) is increased by 24.4%, 40%, and 42.2% at 4, 8, and 12 weeks; respectively. This study noted 16.6% of placebo reporting aphrodisia at week 4, which did not occur at either week 8 or 12.^[22] This aphrodisiac effect has also been noted in experienced athletes that were otherwise healthy, as 2g of a 5:1 extract of Maca taken for 2 weeks was associated with improved scores on a sexuality rating scale (Sexual Desire Inventory^[25]), with more improvement seen with dyadic sexual desire (sexual desire towards others) rather than solitary sexual desire.^[26]

In men with mild erectile dysfunction, both Maca (2400mg) and placebo resulted in significant improvements in scores on the IIEF-5 (rating scale for erectile dysfunction) but the degree of increase seen with Maca was significantly better than that seen with placebo; Maca appeared to be more potent in those with poorer scores.^[27]

One trial has been conducted using Maca root where depressed outpatients (17 women, 3 men) were recruited over a period of 10 months that met the conditions for anti-depressant induced sexual dysfunction using either 1.5g or 3g Maca daily over 12 weeks noted that according to the MGH-SFQ^[28] and ASEX^[29] questionnaires there was significant improvement across both dosage groups, with more efficacy occurring in high dose Maca.^[30] Libido reached significance according to one survey (ASEX), and self-reported sexual enjoyment was increased.^[30]

In human interventions, appears to show statistical significance in a variety of different population subsets

Female rats subject to a forced swim test given 1g/kg Maca not that Maca possesses anti-depressant effects, reducing immobility to 76.4-87.4% of baseline.^[8] This study also noted that although Yellow and Red Maca exerted anti-depressant effects, that Black Maca was slightly more effective.^[8]

One rat study suggested anxiolytic effects due to performance on an elevated maze plus test.^[24]

A reduction of both depression and anxiety has been noted in postmenopausal women ingesting 3.5g Maca daily for 6 weeks, as assessed by the respective subscales on the Greene Climacteric Scale.^[31]

Human studies are mixed, but Maca might aid in anxiety and depression assuming a pre-existing stressor or condition

A comparative study in ovariectomized female rats using 1g/kg Maca (Red, Yellow, and Black) all three forms appeared to improve cognition as assessed by a water finding task with Black outperforming the other variants.^[8] A similar task was employed with Black Maca in a test to see neuroprotective effects against scopalamine, and it was found that the Maca treated groups trended (nonsignificant) to outperform control.^[32]

Is showing trends to improve cognition in otherwise normal rats, but is not overly significant and mechanisms unknown

In the study injected scopalamine (which induces acetylcholinesterase) it was found that Maca suppressed this increase in AChE to a level not significantly different than placebo^[32] and was able to decrease an increase in AChE in menopausal rats.^[33] No influence was found on Monoamine Oxidase activity^[32] which has been replicated,^[33] this observation is a surprising result due to presence of some β-carboline compounds^[19] that have been associated with MAO inhibition previously.^[34]

One in vitro test with neurons isolated from Crayfish noted dose-dependent protection against hydrogen peroxide when neurons were pretreated 3 hours before H₂O₂ treatment, this pentane extract of Maca possessed an EC₅₀ of approximately 2.8μg/mL and exerted 88% protection when 30μg/mL was used.^[35] When tested in vivo, an injection of 3mg/kg bodyweight pentane Maca extract significantly reduced the infarct size from ischemia (indicative of protective effects) to 58.6% the size of control; higher doses (10, 30mg/kg) actuall exacerbated damage.^[35]

A study conducted with varying doses (0.125, 0.25, 0.5, and 1g/kg) Black Maca in a model of alcohol-induced memory impairment when both were administrated orally for 28 days noted that all doses of Black Maca were able to abolish the increase in escape latency (time required for the mice to remove itself from the maze) seen with alcohol, and trended to improve time relative to control.^[36]

Protection against scopalamine has been noted with Black Maca,^[32] this study fed both the aqueous (0.5, 2g/kg) and hydroalcoholic (0.25, 1g) extracts for 35 days and injected the acetylcholinergic toxin scopalamine prior to testing, and it was demonstrated that Maca administration was able to prevent the scopalamine-induced reduction in performance (via Moris Maze test) with no difference between extracts or doses, but the lower doses of each extract trending to outperform control.^[32]

Appears to be a potent neuroprotective agent, and Black Maca appears to be more neuroprotective than other ecotypes; currently not known why

Currently, one study suggests that Maca may possess blood pressure reducing properties via ACE inhibitory activities in a dose-dependent manner, with the heat-treated extract outperforming the raw extract.^[6] That being said, one preliminary toxicological study with 0.6g Maca daily noted a small but significant increase in diastolic blood pressure.^[37]

Interactions with cardiovascular healthy currently not known

Maca has been tested to its ability to inhibit carbohydrate uptake in the intestines, and an in vitro study assessing both raw and toasted extracts of maca noted that (in inhibiting α-glucosidase and α-amylase) noted that both extracts inhibited raw maca inhibited α-glucosidase in the 20-40% range (fairly weak) while raw maca weakly inhibited α-amylase (approximately 10%) while toasted maca failed to inhibit α-amylase.^[6] These results were not correlated to the polyphenolic content of Maca, which was poor.

One rat study using Maca at 1% food weight in an animal model of heredity high triglycerides (worsened by a sucrose-rich diet for two weeks) noted that Maca was able to reduce plasma cholesterole (LDL-C and vLDL-C) as well as triglycerides, and glucose was reduced (thought to be secondary to the reduction in triglycerides).^[38] This study used 0.02% rosiglitazone as an active control, which outperformed Maca.^[38]

Overall, nothing too spectacular known about Maca and its interactions with Glucose metabolism

In one pilot study using 8 experienced endurance cyclists with no changes to their diet or training aside from a single rest day prior to the trial, high dose Maca (2g of a 5:1 extract; bioactivity of 10g) taken for 2 weeks prior to the trial ride noted a significant reduction in time to complete the trial from 57.62+/-3.14min to 56.56+/-2.68min (1.84% reduction) when comparing baseline to post-supplementation; placebo tended to improve but it failed to reach significance.^[26] When comparing the performance of placebo and Maca at the time trail rather than against themselves from baseline, there were no significant differences.^[26]

Currently weak evidence for assessing the interaction of Maca and physical activity, with the preliminary results suggesting nothing special

One comparative study has been conducted with a polyherbal blend of Maca (1500mg) with 300mg Uncaria guianensis against 1500mg glucosamine sulfate, and although both treatments were associated with significant improvement rates the polyherbal blend was associated with less 'rescue' treatment (paracetamol given to participants and to be consumed when joint pain was not alleviated by treatment).^[39] This study recieved funding from the company producing the polyherbal blend.^[39]

1.5g and 3g of Maca for 12 weeks failed to increase circulating testosterone levels in healthy men.^[40] These same doses have been used in a 12 week study by other authors in men, and it was noted an increase in aphrodisia (as assessed by self-report) that reached 24.4%, 40%, and 42.2% of the subjects in Maca at 4, 8, and 12 weeks (respectively) while placebo had no increase at weeks 8 and 12; this increase in aphrodisia was independent of testoterone, which did not differ between groups.^[22] No androgenic effects or increases in testosterone are seen in postmenopausal women taking 3.5g Maca daily for 6 weeks.^[31]

Maca does not appear to have significant androgenic interactions beyond circulating testosterone, as this study failed to note any interactions of Maca components with the androgen receptor.^[41]

No current study has established a testosterone enhancing ability of Maca or its components

One rat study using lead to induce testicular damage noted that, while 2.2g Maca extract (boiled hypocotyls) was able to preserve spermatogenesis that it was unable to prevent the decline in testosterone levels induced by lead.^[42] A similar dose of 2g/kg, which is comparable to traditional usage of Maca, has also failed to influence testosterone levels in otherwise healthy rats.^[43]

Interestingly, one case study noted that they detected elevated testosterone in a female taking Maca but that this was attributed to Maca interfering with the testing protocol; a higher precision test revealed a normal testosterone level.^[44]

Circulating estrogen was not influenced with 1.5g or 3g Maca daily for 12 weeks in otherwise healthy men,^[40] and these results have been replicated elsewhere with similar dosing and length of study^[22] and in postmenopausal women using 3.5g daily for 6 weeks.^[31]

Currently no evidence to suggest that it works via increasing estrogen levels in vivo

One study using MCF-7 breast cancer cells (a cell line responsive to estrogen) noted that Maca at 0.1-100ug/mL was able to induce proliferation and induced notable estrogenicity at 100-200ug/mL concentration, but was less potent than physiological concentrations of estrogen;^[45] the potency was comparable to that of Silymarin from Milk Thistle.^[45] Estrogenic effects have been seen in vivo when ovariectomized rats were given 0.24g/kg ethanolic extract of Maca (equivalent to 1.25g/kg root extract), where the measured uterine weight after 28 weeks was 121.9% of ovariectomized control but 59.5% that of non-menopausal control.^[46] Another study using a lower dose of three variants of Maca for 4 weeks failed to establish estrogenic effects,^[47] and estrogenic effects have also failed to be observed in other in vitro assays.^[31]

Some evidence for Maca acting directly as a phytoestrogen, but evidence is currently mixed and practical relevance of this information unknown

In a 12 week double blind study using Maca at either 1.5g or 3g of Maca taken in three divided doses and a third group taking 1.5g as a single dose, the men in this study had no difference based on timing (and thus both 1.5g groups were pooled together) and there were no significant influence on follicle-stimulating hormone;^[40] similar results have been found in postmenopausal women ingesting 3.5g Maca daily for 6 weeks.^[31]

A 12 week study in healthy men taking either 1.5g or 3g of Maca daily failed to significantly influence circulating luteinizing hormone levels at 4, 8, or 12 weeks in time.^[40] A lack of effect has also been observed following 3.5g daily ingestion for 6 weeks in post-menopausal women.^[31]

In vitro, the methanolic and water extracts of Maca appear to have either no influence on hepatocyte function at 0.1-10ug/mL concentrations as assessed by MTT, LDH, and AST leakage (indicative of membrane permeability) and when incubated for a prolonged period of time (72h) actually acted to reduce leakage of LDH and AST to 61.2% and 55.6% of control; respectively, with concentrations over 1ug/mL being significantly protective of LDH leakage.^[45] However, this in vitro study appears to oppose preliminary human toxicological data where the only side-effect seen with 0.6g Maca taken daily for 90 days was a slight increase in serum AST levels.^[37] The reason for this discrepancy is not know, but is likely not mediated by oxidation as Maca was demonstrated in this study to possess relatively weak anti-oxidant properties, as a DPPH assay indicated that the water and methanolic extract had an IC₅₀ value of 3.46+/-0.16mg/mL and 0.71+/-0.10mg/ml, respectively.^[45] Maca has been associated with an increase in liver Superoxide Dismutase levels as well as increased serum reduced gluathione, although TBARS and CD (markers of lipid peroxidation) in serum are unaffected.^[38]

Unclear effects on the liver

The variant of Red Maca appears to be able to suppress prostatic growth, where Black and Yellow are ineffective at doing so.^[11] In this study, rated given 2g/kg of an aqueous extract of Red Maca daily for a week had smaller ventral prostatic weight relative to control, and over a period of 14 and 42 days Maca normalized the increase seen in prostatic weight following testosterone injections, the increase in seminal vesicle weight was also abolished.^[11]

The active ingredient may be benzyl glucosinolate, as the HPLC peak of Red Maca in the first study coincided with these components^[11] and a laster study established a dose-dependent decrease in prostate size when testing benzylglucosinolates at 0.02-0.08mg/mL^[18] and replicated the reduction in prostate size with 0.1mg glucosinolate orally over 14 days (although this study did not find complete abolishment of the increase).^[18] This study also noted that extracts delivering 0.1mg benzylglucosinolate (exact extract given not listed) was more effective in suppressing prostatic weight gain than 0.1mg finasteride, without affecting the weight of seminal vesicles^[18] (opposite the results observed previously with 2g/kg^[11]). A second study has been conducted with Red Maca using finasteride as a positive control and in rats comparing Red Maca (0.01, 0.05, 0.1, 0.5g/kg) confirmed dose dependence with 0.1g/kg reaching significance, while a second part of the study using 0.6mg/kg finasteride noted that 0.1 and 0.5g/kg Red Maca (0.64% benzylglucosinolate content) was more effective in suppressing prostate growth without influencing seminal vesicle weight.^[48] The authors hypothesized a mechanism of action downstream of DHT conversion.^[48] An increase of testosterone in these rats are not seen with Maca, which is normally the result of 5α-reductase inhibitors such as Finasteride^[49] or Fenugreek, suggesting no interaction on the level of the 5-AR enzyme.

Highly promising results in Red Maca, possibly as potent as finasteride in reducing prostate size (biomarker for prostate cancer risk); studies need to be replicated outside or Peru (producer and exporter of Red Maca, this issue may be similar to policosanol and Cuba) and conducted in humans

The role of Benzyl Glucosinolate (apparently active ingredient in suppressing prostatic growth) in relation to spermatogenesis is not known, as the above studies suggest that it does not play a role but passively allows testosterone to induce seminal vesicle size while the only other herb expressing Benzyl Glucosinolate, Tropaeolum tuberosum, is known to suppress spermatogenesis^[50] (although causation was not placed on the active ingredient). Some authors suspect polyphenolics may play a role, but currently this is not assessed.^[51]

Benzyl Glucosinolate is the systemic name for the glucosinolate known as Glucotropaeolin, which tends to comprise 80-90% of total glucosinolates by weight; surprisingly, the content of Glucotropaeolin has been found to not differ significantly between ecotypes of Maca, with one study reporting contents of 81.37% ,80.30%, and 80.25% for Red, Yellow, and Black respectively.^[9]

Additionally, Red Maca has been found to suppress the increase in prostate zinc levels which facilitate the conversion of testosterone to dihydrotestosterone (DHT); this study also found significant correlations between prostatic zinc levels and the prostate weight, although the correlation coefficient was r=0.76.^[52]

Although Red Maca is associated with decreased prostate size more than the other strains, it seems this may not be due to the Benzyl Glucosinolate content as this does not differ significantly between ecotypes; possibly a currently unknown molecule (or bias in studies form Peru) are to blame/credit

In a study on lead-induced testicular damage where rats were fed lead for 35 days and Maca was introduced on day 18, it was demonstrated that 2.2g/kg Maca daily (boiled hypocotyl extract) acted to attenuate the reduction in seminal vesicle weight that occurred from lead exposure while preserving the weight of the testicle.^[42]

In regards to spermatogenesis, it has been reported that Black Maca has more beneficial effects on spermatogenesis relative to Yellow and Red^[43] as the increase in daily sperm production seen with Yellow and Red sometimes fails to reach statistical significance.^[10] A comparative study between different extracts of Black Maca over 7 days noted that the ethyl acetate fraction was the most effective fraction for increasing daily sperm production although the chloroform extract appeared to be the one that increased sperm count in the vas deferans while both were equally effective in increasing sperm count in the epididymus.^[53] In general, improvements in daily sperm production can be seen from day 1 of supplementation in rats^[43] and improvements in sperm count can be seen independent of increased daily sperm production.^[54] These increases in daily sperm production appear to be related to increasing the onset of spermatogenesis.^[55][56][57]

Maca is also able to reverse suppression of spermatogenesis and sperm count induced by lead even when lead exposure precedes and continues through Maca administration^[42] and has been associated with preserving the reduction in spermatogenesis induced by high elevation.^[5] Interestingly, this conclusion could be an explanation as to why Maca has such an impressive history of fertility usage as it is grown exclusively in heights of 4000-4500m above sea level while this study was conducted at 4340m.^[3]

Maca in general appears to be somewhat protective of the testicles, while the variant of Black Maca appears to be most effective in increasing the production of sperm (and theoretically fertility)

No significant toxicity has been reported in human consumption with Maca root, with one study reporting that 0.6g Maca for 90 days was associated with an increased serum ALT and diastolic blood pressure.^[37] and rats have tolerated up to 5g/kg bodyweight without adverse effects.^[58] In human trials of up to 3g of Maca a day is well-tolerated, and the traditional method of boiling up to 20g of Maca to make into juice has not currently been associated with much toxicity.^[59]

Not too much toxicological information on Maca

Currently, the only evidence investigating a link between Maca consumption and Pregnancy is one conducted in mice where 1g/kg lyophilized (2.16g/kg dry weight) Maca, correlating to traditional usage amounts and consumed prior to and shortly after fertilization, noted increased litter size without any influence on gender ratios and not associated with any adverse pup morphology or viability.^[60] This was independent of any increases in implantation rates, the fertility index, or pup survival; all of which were similar between groups. No human evidence on safety nor adverse reports appear to exist.

Currently not known if it is safe for pregnancy or not, but appears to be somewhat promising to enhance female fertility based on animal studies