Origin & Historical Context

Maca is an annual cruciferous root vegetable and one of 249 known Lepidium species of plants [2]. It belongs to the same botanical Brassicaceaefamily as the turnip, cabbage, mustard, and broccoli, yet it is phytochemically distinct from this vegetable group [3]. 

Geographic Origin

Maca is indigenous to the Andes Mountains and thrives at high altitudes, typically between 3500 and 5000 meters above sea level. The plant is native to regions in Peru and Bolivia. Archaeological evidence indicates cultivation in the central Peruvian Andes (specifically Junín province) dating back over 2000 years, around 700 to 600 BC.

Cultural Origins

Maca was a dietary staple of the native Peruvians, who regularly consumed the dried hypocotyl in amounts often exceeding 20 grams daily. The Incan people regarded maca as their most sacred plant and referred to it as the "food of the brain" because they believed it provided happiness and balance during stress. Historically, dried maca roots were a valued commodity that could be preserved for years and traded for staple foods with communities living at lower altitudes.

Traditional Medicine Systems and Historical Use (Patterns)

Maca has been incorporated into traditional Peruvian systems for centuries for its dual purpose as a food source and therapeutic agent.

Traditional Uses and Early Associations:

• Energy and Vitality: Maca was traditionally used for enhancing energy, vitality, and libido. Some native sources specified that it was used for its energizing properties rather than specifically as an aphrodisiac.

• Fertility: Early reports from Spanish chroniclers in the mid-17th century emphasized its value for improving fertility, recommending it for cattle reproduction in high-altitude lands and noting its consumption by women who struggled to conceive.

• General Health: It was recognized as a tonic for postmenopausal women and was traditionally associated with treating respiratory ailments and rheumatic pains.

• Preparation: The traditional way to consume maca was to use the dried root (rather than fresh) and prepare it boiled in water.

Early Correlations / Observed Contexts Distinguishing the Different Types of Maca

The maca hypocotyls exhibit a range of external colors or phenotypes, with up to seventeen different colors identified, though the majority of research focuses on black, red, and yellow varieties. These color differences correspond to variations in phytochemical profiles and traditionally observed biological responses.

Pre-Clinical Biological Rationale (Mechanism-Level Education)

Maca (Lepidium meyenii) is an area of increasing modern research, moving beyond its traditional use as an adaptogen to explore targeted pharmacological applications for specific phenotypes (colors) and extracts.

Pharmaceutical Lineage & Drug-Class Comparisons

Maca is primarily researched as a non-hormonal, non-toxic, and low-cost alternative or adjunct to conventional pharmaceuticals, particularly those targeting endocrine and sexual health.

Natural vs. Synthetic / Standardization Forms

Maca research focuses on standardizing the natural product itself, particularly concerning different preparations and their concentration of bioactive compounds. The United States Pharmacopeia (USP) is working on finalized monographs for maca root, maca root powder, and maca root glucosinolates dry extract to address product quality, identity, purity, and contaminant limits.

• Raw vs. Gelatinized: Gelatinization is a processing method involving short-term high pressure, temperature, and moisture applied to dried, pulverized maca. This process creates a more digestible product (by reducing high starch content), increases the bioavailability of actives, and can reduce goitrogen content. However, raw maca may have about 20% higher glucosinolates than the gelatinized form.

• Extracts and Concentration: Specific extracts, such as spray-dried extracts, concentrate phytochemicals and often contain components that might not be consumed when maca is eaten as a traditional food. Highly refined extracts are currently being developed and tested for certain biomarker classes, such as Maca-BG1.2TM (standardized to at least 1.2% benzyl glucosinolate).

Metabolism, Cellular/Enzymatic/Endocrine Mechanisms

The biological actions of maca stem from a synergistic mix of unique secondary metabolites, particularly the macamides, glucosinolates, and macaenes.

Endocrine and HPTAG Axis Modulation

Maca is classified as an adaptogen due to its potential to modulate hormones and the immune system and promote optimal homeostasis.

• HPTAG Axis (Hypothalamus-Pituitary-Thyroid-Adrenal-Gonad): Research indicates that standardized formulations combining different maca colors can modulate the entire endocrine axis.

• Ovarian/Menopausal Hormone Balance: Specific proprietary formulations (e.g., Maca-GO®) have demonstrated significant modulation of the hypothalamic–pituitary–ovarian (HPO) axis in perimenopausal and early postmenopausal women. This modulation resulted in statistically significant increases in estradiol (E2) and progesterone (P), alongside decreases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH), all without introducing exogenous hormones.

• Adrenal Health: Maca contributes to adaptive responses and modulates the HPTAG axis by influencing the stress response, notably by reducing cortisol and adrenocorticotropic hormone (ACTH) levels in clinical trials involving women.

Cellular and Enzymatic Mechanisms

• Neuro-Endocannabinoid System: Macamides, which are benzylated alkamides unique to maca, are structurally similar to the endogenous cannabinoid anandamide. Macamides exert their effects by inhibiting the enzyme Fatty Acid Amide Hydrolase (FAAH), preventing the degradation of anandamide. This mechanism is linked to maca's anti-fatigue, mood-enhancing, and neuroprotective properties.

• Glucose Metabolism: The ability of black maca to reduce glycemia is suggested to involve activation of the AMP-activated protein kinase (AMPK) pathway, enhancing glucose uptake in insulin-resistant cells.

• Detoxification and Antioxidant Defense: Macamides have been noted to potentially activate the Nuclear Factor Erythroid 2-related Factor (Nrf2) pathway, a critical mediator of intrinsic cellular defenses against oxidative stress.

Areas of Active Research

Preclinical (animal model) and clinical (human) studies explore a wide array of potential applications for maca.

Evidence Tier Summary

The scientific evidence for maca's efficacy is varied, highly dependent on the phenotype studied, the outcome measured, and often limited by small sample sizes, leading to low certainty of evidence for many applications.

• RCTs (Randomized Controlled Trials): A review of clinical trials shows that approximately 50% of published studies fail to specify the maca color used. Black maca has the most publications (six) as a single phenotype in clinical trials, followed by yellow maca (two) and red maca (one study testing both red and black).

• Systematic Reviews/Meta-Analyses (SR/MA):

    ◦ Erectile Dysfunction (ED): A meta-analysis of two RCTs found that maca had a positive effect on erectile function in men with mild ED. However, the certainty of evidence (CoE) for this outcome was ranked as LOW due to small sample sizes and methodological concerns in the underlying RCTs.

    ◦ Menopausal Symptoms: SR/MA indicates that maca consumption is linked to the reduction of menopausal symptoms, often based on specific combined formulations (e.g., Maca-GO®) proven effective in multiple RCTs.

    ◦ Semen Quality: SR/MA suggests that maca may improve semen quality parameters (e.g., concentration, motility), but the evidence is inconsistent or considered insufficient to draw firm conclusions due to the common failure of primary studies to identify the specific maca color used.

The complexity of Maca's effects is analogous to a master key ring: rather than a single master key (single chemical compound) for one lock 

(mechanism), Maca offers multiple keys (macamides, glucosinolates, etc.) in varying ratios (phenotypes) that interact to operate complex mechanisms (the HPTAG axis or endocannabinoid system), meaning the efficacy is dependent on selecting the right combination for the right job.

Patient Populations

Maca (Lepidium meyenii) is used by a broad range of individuals, historically as a dietary staple and traditionally for general wellness, but modern research suggests specific populations or phenotypes (colors) are targeted for particular physiological effects.

Maca is generally for:

1. Individuals Seeking Hormone and Endocrine System Support

Maca is classified as an adaptogen, a substance that may modulate hormones and the immune system to promote optimal homeostasis. Unlike a pharmaceutical agent that targets a single receptor or hormone, some maca formulations (such as Maca-GO®) modulate the entire endocrine system, including the hypothalamus–pituitary–thyroid–adrenal–gonad (HPTAG) axis.

• Women in Peri- and Postmenopause: Maca is researched as a non-hormonal alternative to Hormone Replacement Therapy (HRT). Specific concentrated maca phenotype combinations (Maca-GO®) have demonstrated significant modulation of the hypothalamic–pituitary–ovarian (HPO) axis, leading to statistically significant increases in estradiol (E2) and progesterone (P), and decreases in Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) in postmenopausal women.

    ◦ It is used clinically to reduce menopausal symptoms, including hot flushes, night sweats, nervousness, and depression.

    ◦ It also showed benefits for bone health, increasing forearm bone density scores in postmenopausal women who experienced decreases in the placebo group.

• Men with Androgen Deficiency Symptoms: While maca typically does not significantly increase serum testosterone (T) or free T levels, it has been shown to improve symptoms associated with late-onset hypogonadism (androgen deficiency symptoms).

    ◦ A clinical trial using gelatinized black maca powder (5 g/day) significantly improved scores for Aging Males’ Symptoms (AMS), International Index of Erectile Function (IIEF), and International Prostate Symptom Score (IPSS).

• Individuals with Chronic Stress/Fatigue: Maca is researched for its adaptogenic and vitality-enhancing properties. It can modulate the stress response, notably by reducing levels of cortisol and adrenocorticotropic hormone (ACTH).

2. Men for Sexual and Reproductive Health

Maca is marketed as a "Testosterone Booster" and "Peruvian Viagra". However, consumers should be cautious, as most ingredients in "T booster" supplements are not supported by academic literature to increase T levels. Maca is used for:

• Improving Libido and Sexual Desire: In men, maca supplementation increased sexual desire independent of changes in serum T or E2 levels. This benefit was noted in men with mild erectile dysfunction (ED) and in healthy men.

• Mild Erectile Dysfunction (ED): Maca showed a positive effect on erectile function in men with mild ED. However, the evidence tier for this is considered LOW certainty, and the efficacy may be dose-dependent, with a higher dose (2.4 g/day) over a longer duration (12 weeks) showing positive results, whereas a lower dose (1.2 g/day) over a shorter duration (8 weeks) did not.

• SSRI-Induced Sexual Dysfunction: Maca root, particularly at a high dose (3.0 g/day), significantly improved sexual dysfunction scores in remitted depressed outpatients concurrently taking Selective Serotonin Reuptake Inhibitors (SSRIs).

• Spermatogenesis/Fertility: Maca use is traditionally associated with fertility enhancement.

    ◦ Black Maca extracts have consistently been shown to impact spermatogenesis and improve sperm count and production in animal models, often preferentially over other colors.

    ◦ Unspecified maca products have shown statistically significant increases in sperm concentration in men with mild asthenozoospermia and/or oligozoospermia.

• Prostate Health: Red Maca is the most vigorously researched phenotype for its ability to inhibit benign prostatic hyperplasia (BPH) (enlarged prostate) in animal models. Red maca reduced prostate size in mice and rats, similar to the action of the pharmaceutical drug finasteride, but via a different anti-inflammatory pathway.

3. Athletes and High-Altitude Dwellers

• Athletic Performance and Endurance: Black maca has been shown in human clinical trials to improve muscle endurance, agility, muscle strength, and power in elite athletes. It can also reduce ammonia levels and increase muscle strength in racket athletes.

• Chronic Mountain Sickness (CMS) and Altitude Adaptation: Maca (specifically red and black extracts) improved mood, energy, health status, and reduced CMS scores in adult human subjects living at high altitudes.

    ◦ Red maca was noted to be more effective at improving mood, energy, and CMS scores than black maca.

    ◦ Black maca specifically helped reduce abnormally high hemoglobin levels observed in highlanders, a common sign associated with CMS.

4. Individuals Seeking Specific Health Benefits (Phenotype Dependent)

Due to distinct phytochemical profiles, specific colors of maca are targeted for unique effects:

• Black Maca (Memory/Cognition): Preclinical studies suggest black maca is the most effective for enhancing memory and learning, partly due to its antioxidant content and acetylcholinesterase inhibitory activities.

• Red Maca (Bone and Skin Health): Red maca showed a protective action on bone structure in animal models and promoted skin wound healing in mice exposed to high-altitude stress.

• Yellow Maca (General Balance and Resilience): As the most common and traditionally consumed variety (60–70% of the harvest), yellow maca is historically used by men, women, and children daily to maintain balance and build resilience. Preclinical data suggest a potential role in muscle hypertrophy and female fertility, reportedly increasing litter size in mice.

The efficacy of maca is highly dependent on using a well-defined product whose color, cultivation location, preparation method (raw vs. gelatinized vs. extract), and concentration/dose have been standardized and ideally verified through clinical testing

Safety, Interactions & Quality Considerations

The safety, interactions, and quality assurance of maca products are recognized as critical variables influencing their clinical use and efficacy, especially given the distinct properties of red, yellow, and black maca phenotypes.

Bioavailability & Dose Considerations 

The clinical efficacy of maca is influenced heavily by the dose, duration, and preparation method, often leading to inconsistent results in human trials.

Dose and Duration:

• Traditional consumption by native Peruvians was high, often exceeding 20 grams daily of dried hypocotyl as a food staple.

• Clinical trials most often utilize daily doses ranging from 1.5 g to 5 g.

• A direct dose-response relationship has been observed in some studies; for instance, in trials for mild erectile dysfunction, consuming a higher dose (2.4 g/day) over a longer duration (12 weeks) reported positive results, while a lower dose (1.2 g/day) over a shorter period (8 weeks) did not demonstrate beneficial effects.

Preparation and Bioavailability:

• Raw vs. Gelatinized: Maca hypocotyls contain high starch, which can cause digestive issues. The process of gelatinization (using pressure, heat, and moisture) reduces this starch content, creating a product that is more digestible and potentially more bioavailable. Gelatinization may also help reduce goitrogen content, which can interfere with thyroid activity. However, raw maca may retain about 20% higher glucosinolates compared to the gelatinized format.

• Extracts: Highly concentrated extracts, like the spray-dried extracts of red and black maca used in clinical trials, contain concentrated phytochemicals, demonstrating efficacy at a dose of 3 g/day.

Known Safety Profile & Common Side Effects

Maca (Lepidium meyenii) is generally regarded as safe, non-toxic, and well-tolerated in humans, supported by preclinical studies that demonstrate low toxicity even at high doses. For example, preclinical tests show acute oral toxicity (LD50) greater than 7.5 g to 15 g/kg body weight in rats and mice, and it was found safe for chronic use of up to 90 days.

Specific Maca Phenotype Safety: A randomized, controlled study testing spray-dried extracts of black maca and red maca (3 g daily for 12 weeks) in adult subjects living at low and high altitudes reported good acceptability and no serious adverse effects.

Common and Rare Side Effects:

• Common/Transient: Clinical trials involving oral administration of maca powder or capsules have reported minor, transient side effects such as gastrointestinal upset, headache, and irritability. Since raw maca is high in starch, using gelatinized maca may be preferable to minimize digestive issues.

• Moderate Effects: One study involving patients with metabolic syndrome who took 0.6 g/day of unspecified maca powder for 90 days reported a moderate elevation in a liver enzyme (AST) and diastolic blood pressure (DBP).

• Rare Adverse Events: Case reports have noted isolated severe effects, including vaginal bleeding in a young woman and a manic episode in a man with no prior psychiatric history, though these reports are rare.

Contraindications / Medication Interactions

Due to Maca’s observed ability to modulate the hypothalamus-pituitary-thyroid-adrenal-gonad (HPTAG) axis, certain clinical situations may warrant caution:

• Hormone-Sensitive Conditions:    Products of sufficient dose and quality that modulate the endocrine system may be contraindicated for individuals with a personal or family history of hormone-sensitive cancers.

• Drug Interactions (Hypothetical): Limited information suggests a possible interaction between maca and the tetracyclic antidepressant mianserin in one case report. The proposed mechanism involved maca potentially inhibiting the cytochrome oxidase CYP3A4, thereby increasing the mianserin concentration.

• SSRI Mitigation: Conversely, maca has demonstrated a beneficial interaction in clinical settings. A pilot dose-finding study determined that a high dose of maca root (3.0 g/day) significantly improved sexual dysfunction scores in outpatients successfully treated with Selective Serotonin Reuptake Inhibitors (SSRIs).

• Testosterone Assay Interference: A single case report demonstrated that maca consumption can cause analytical interference in the plasma testosterone immunoassay in women, leading to a falsely elevated result.

Quality Risks (Identity, Adulteration, Variability, Contaminants)

The quality and chemical profile of maca products are highly inconsistent, representing significant risks to identity and expected efficacy:

1. Variability by Phenotype and Origin: The chemical composition of maca varies significantly based on its color (phenotype), geographic origin (altitude, soil), and post-harvest processing methods. This high variability means that selecting the correct product for a specific purpose is highly challenging:

• Color-Specific Profiles: Although up to seventeen colors exist, scientific efforts focus mainly on black, red, and yellow varieties. These colors possess differential phytochemical compositions; for instance, in one study comparing extracts, red maca predominated in GABA, while black maca had higher concentrations of macamides and fatty acids.

• Cultivation Site: The location where maca is grown significantly affects its secondary metabolites, potentially more than the color itself, leading to different concentrations of macaenes and macamides.

2. Adulteration and Mislabeling:

• Dilution: Maca powder products have been reported in some instances to be diluted with cheaper powders like corn, wheat, or yam.

• Inconsistent Claims: Supplements making "Testosterone Boosting" claims are often not supported by academic literature, with only about 24.8% of ingredients reviewed having data to support such claims.

3. Contaminants and Microbial Risk:

• Toxic Metals: Maca roots can accumulate heavy metals (such as arsenic, cadmium, and lead) from contaminated soil, particularly in areas of Peru affected by the mining industry. Manufacturers often rely on testing the land prior to cultivation or testing the final product to mitigate this risk.

• Microbial Risk: Different colors exhibit different stability profiles. For example, yellow maca powder was found to have consistently higher microbial contamination (specifically Gram-positive aerobic Bacillus strains) in comparison to black maca and red maca, necessitating careful storage based on color.

4. Quality Control Solutions (USP): The United States Pharmacopeia (USP) is addressing these risks by working to establish quality monographs for maca root and its derivatives to set standards for identity, purity, composition, and contaminant limits. Consumers can look for the USP Verified Mark, which indicates the product:

• Contains the ingredients and potency listed on the label.

• Does not contain harmful levels of specified contaminants.

• Is manufactured according to FDA current Good Manufacturing Practices (cGMPs).

The highly complex nature of maca—where color, preparation, and origin determine its chemical effect—underscores why research often lacks coherence. It is like trying to identify the flavor profile of a vintage wine without knowing the grape varietal, the specific vineyard, or the aging process; lacking any one detail means the outcome is unpredictable and unrepeatable.

Krafted Formulation Rationale - Our Difference

Krafted Supplements approaches botanical formulation through a clinical, systems-biology lens, integrating ethnobotanical history with modern pharmacology, standardization science, and future regulatory readiness. Maca is not treated as a generic “adaptogen,” but as a phenotype-dependent, dose-sensitive biologic, where color, preparation, and sourcing materially alter physiological outcomes.

Our Maca Root Blend is intentionally designed to reflect this complexity while remaining safe, transparent, and scalable.

Sourcing Standard

Krafted Maca is sourced exclusively from high-altitude Andean cultivation zones (≥3,800 m) in Peru, where environmental stressors (UV exposure, hypoxia, temperature variance) drive the synthesis of maca-specific secondary metabolites (macamides, glucosinolates, macaenes).

Sourcing criteria include:

• Verified botanical identity: Lepidium meyenii (voucher specimens maintained)

• Altitude-verified cultivation (not lowland or greenhouse maca)

• Post-harvest drying of hypocotyls (traditional preservation method)

• Segregated harvesting by phenotype (black, red, yellow)

• Soil screening for heavy metals prior to cultivation

This prevents dilution with lower-potency maca grown outside its native ecological niche and preserves phenotype-specific phytochemical profiles.

Standardization Targets

Rather than standardizing to a single isolated compound, Krafted targets functional phytochemical classes known to drive maca’s biological effects.

Primary standardization priorities:

• Macamides & macaenes (neuroendocrine and endocannabinoid-adjacent activity)

• Glucosinolates (phenotype-dependent anti-proliferative and metabolic signaling)

• Fatty acid profile (black maca enrichment)

• GABA enrichment (red maca contribution)

Each phenotype is included at a purposeful ratio to avoid dominance of any single endocrine signal, supporting system-level homeostasis rather than receptor-level overstimulation.

Purity Thresholds & Third-Party Testing Plan

Krafted applies pharmaceutical-adjacent quality controls despite operating within the dietary supplement framework.

Mandatory testing includes:

• Identity confirmation (macroscopy + HPTLC/FTIR)

• Heavy metals (Pb, Cd, As, Hg) — USP <233> limits

• Microbial load (TAMC, TYMC, pathogenic screens)

• Pesticides (USP <561>)

• Mycotoxins (aflatoxins, ochratoxin A)

• Adulterant screening (starch dilution, non-maca fillers)

Each production lot is supported by Certificates of Analysis (COAs) from ISO-accredited third-party laboratories.

Formulation Logic (Why These Ratios, Grades, and Excipients)

Phenotype-Balanced Design

This formulation intentionally combines:

• Black maca (1000 mg) — endurance, metabolic signaling, cognition, spermatogenesis

• Red maca (250 mg) — prostate, bone, mood, inflammatory modulation

• Yellow maca (250 mg) — baseline resilience and endocrine balance

This ratio reflects:

• Black maca’s higher concentration of macamides and fatty acids

• Red maca’s targeted urological and skeletal research profile

• Yellow maca’s traditional role as a daily foundational food

Absorption Optimization

• Black pepper extract (5 mg) is included to modestly enhance bioavailability and digestive efficiency without overstimulating absorption or CYP pathways.

No synthetic hormones, stimulants, or isolated endocrine agonists are included.

Delivery Form Justification : Capsule vs. Powder vs. Liquid

Krafted selected a capsule delivery system for this formulation based on clinical, safety, and compliance considerations.

Capsule advantages:

• Precise phenotype dosing and reproducibility

• Improved palatability vs. raw maca powder

• Reduced microbial risk vs. bulk powders

• Enhanced compliance for long-term use

• Compatibility with future clinical trials and IND-adjacent studies

Liquid formats were excluded due to stability issues and poor preservation of lipid-soluble macamides.

Clinical Mindset & Future FDA Pathway Readiness

Krafted formulates with regulatory foresight, not marketing convenience.

This Maca Root Blend was designed to be:

• Fully traceable (raw material → finished product)

• Dose-rational (aligned with clinical trial ranges)

• Phenotype-defined (color-specific disclosure)

• Excipients-minimal (future IND compatibility)

While currently positioned as a dietary supplement, this formulation architecture supports:

• Future structure–function claim substantiation

• Controlled observational studies

• Potential transition toward FDA-reviewed botanical drug pathways, should a specific phenotype-indication pairing warrant further development

Krafted’s long-term vision is not to blur the line between food and drug - but to respect it, building evidence forward rather than retrofitting claims later.

Regulatory Status & Transparency

Krafted Supplements operates with the understanding that long-term credibility in health products depends on regulatory literacy, documentation discipline, and restraint in claims. Our Maca Root Blend is positioned clearly and intentionally within the U.S. dietary supplement framework while maintaining readiness for more formal regulatory pathways should future evidence warrant advancement.

Dietary Supplement Positioning & Structure/Function Language

This product is marketed exclusively as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA).

Permissible communications are limited to:

• Supporting normal physiological function

• Describing traditional use and nutritional support

• Discussing mechanism-level education without implying treatment

All consumer-facing language adheres to FDA-permitted structure/function claims (e.g., “supports hormonal balance,” “supports energy and resilience”) and is accompanied by the required DSHEA disclaimer.

Labeling Guardrails (No Disease Claims)

Krafted maintains strict internal guardrails to prevent regulatory drift:

• No claims to diagnose, treat, cure, or prevent disease

• No references to named medical conditions (e.g., BPH, depression, diabetes)

• No pharmaceutical comparisons in consumer materials

• No hormone replacement or “testosterone boosting” claims

Clinical literature is used for internal education and formulation rationale, not as marketing copy.

Manufacturing Standards

All products are manufactured in facilities compliant with FDA current Good Manufacturing Practices (21 CFR Part 111).

Quality safeguards include:

• Identity, purity, and potency testing for each raw material

• Finished-product verification prior to release

• Lot-specific Certificates of Analysis (COAs) available upon request

• Full lot traceability from raw ingredient to finished capsule

This ensures reproducibility, safety, and audit readiness.

Documentation Discipline (Internal QC/QA)

Krafted applies biotech-style documentation discipline to supplement manufacturing:

• Internal formulation specifications and deviation logs

• Batch records with acceptance criteria

• COA review and release authorization protocols

• Supplier qualification and re-verification procedures

This internal QC/QA framework supports transparency, post-market accountability, and potential future clinical or regulatory submissions.

References

Core Reviews and High-Value Overviews  

• Ulloa Del Carpio N, Alvarado-Corella D, Quiñones-Laveriano DM, et al. Exploring the chemical and pharmacological variability of Lepidium meyenii: a comprehensive review of the effects of maca. Front Pharmacol. 2024;15:1360422. doi:10.3389/fphar.2024.1360422.

• Minich DM, Ross K, Frame J, et al. Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses. Nutrients. 2024;16(4):530. doi:10.3390/nu16040530.

• Beharry S, Heinrich M. Is the hype around the reproductive health claims of maca (Lepidium meyenii Walp.) justified? J Ethnopharmacol. 2018;211:126–170. doi:10.1016/j.jep.2017.08.003.

• Wang S, Zhu F. Chemical composition and health effects of maca (Lepidium meyenii). Food Chem. 2019;288:422–443. doi:10.1016/j.foodchem.2019.02.071.

• Peres NSL, Bortoluzzi LCP, Marques LLM, et al. Medicinal effects of Peruvian maca (Lepidium meyenii): a review. Food Funct. 2020;11:83–92. doi:10.1039/c9fo02732g.

• Chen R, Wei J, Gao Y. A review of the study of active components and their pharmacology value in Lepidium meyenii (Maca). Phytother Res. 2021;35:6706–6719. doi:10.1002/ptr.7257.

• Zhu H, Hu B, Hua H, et al. Macamides: a review of structures, isolation, therapeutics and prospects. Food Res Int.2020;138:109819. doi:10.1016/j.foodres.2020.109819.

• Huang YJ, Peng XR, Qiu MH. Progress on the chemical constituents derived from glucosinolates in maca (Lepidium meyenii). Nat Prod Bioprospect. 2018;8:405–412. doi:10.1007/s13659-018-0185-7.

Human Clinical Trials 

• Dording CM, Fisher L, Papakostas G, et al. A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for SSRI-induced sexual dysfunction. CNS Neurosci Ther. 2008;14(3):182–191. doi:10.1111/j.1755-5949.2008.00052.x.

• Lee E, Park M, Kim B, Kang S. Effect of Black Maca Supplementation on Inflammatory Markers and Physical Fitness in Male Elite Athletes. Nutrients. 2023;15(7):1618. doi:10.3390/nu15071618.

• Gonzales GF, Córdova A, Vega K, et al. Effect of Lepidium meyenii (Maca) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia. 2002;34:367–372. doi:10.1046/j.1439-0272.2002.00519.x.

• Gonzales GF, Córdova A, Vega K, et al. Effect of Lepidium meyenii (Maca) on serum reproductive hormone levels in adult healthy men. J Endocrinol. 2003;176:163–168. doi:10.1677/joe.0.1760163.

• Zenico T, Cicero AFG, Valmorri L, Mercuriali M, Bercovich E. Maca extract and well-being/sexual performance in mild erectile dysfunction: randomized, double-blind trial. Andrologia. 2009;41:95–99. doi:10.1111/j.1439-0272.2008.00892.x.

• Stone M, Ibarra A, Roller M, Zangara A, Stevenson E. Pilot investigation: maca supplementation, physical activity, and sexual desire in sportsmen. J Ethnopharmacol. 2009;126:574–576. doi:10.1016/j.jep.2009.09.012.

• Stojanovska L, Law C, Lai B, et al. Maca reduces blood pressure and depression in a pilot study in postmenopausal women. Climacteric. 2015;18:69–78. doi:10.3109/13697137.2014.929649.

• Gonzales-Arimborgo C, Yupanqui I, Montero E, et al. Acceptability, safety, and efficacy of oral extracts of black or red maca: randomized, double-blind, placebo-controlled study. Pharmaceuticals (Basel). 2016;9:49. doi:10.3390/ph9030049.

• Shin D, Jeon SH, Piao J, et al. Efficacy and safety of maca in late-onset hypogonadism symptoms: randomized, double-blind, placebo-controlled trial. World J Mens Health. 2023;41:692–700. doi:10.5534/wjmh.220112.

• Brooks NA, Wilcox G, Walker KZ, et al. Maca in postmenopausal women: psychological symptoms and sexual dysfunction not related to estrogen/androgen content. Menopause. 2008;15:1157–1162. doi:10.1097/gme.0b013e3181732953.

• Melnikovova I, Fait T, Kolarova M, et al. Effect of L. meyenii on semen parameters and serum hormones: double-blind, randomized, placebo-controlled pilot. Evid Based Complement Alternat Med. 2015:324369. doi:10.1155/2015/324369.

• Melnikovova I, Russo D, Fait T, et al. L. meyenii in infertile patients: randomized, double-blind, placebo-controlled trial. Phytother Res. 2021;35:6359–6368. doi:10.1002/ptr.7287.

Safety Signals, Interactions, and Adverse Events 

• Valerio LG, Gonzales GF. Toxicological aspects of cat’s claw and maca: a critical synopsis. Toxicol Rev.2005;24:11–35. doi:10.2165/00139709-200524010-00002.

• Valentová K, Stejskal D, Bartek J, et al. Maca and yacon with silymarin: in vivo safety assessment. Food Chem Toxicol. 2008;46:1006–1013. doi:10.1016/j.fct.2007.10.031.

• Srikugan L, Sankaralingam A, McGowan B. Testosterone assay interference in a female taking maca: case report. BMJ Case Rep. 2011:bcr0120113781. doi:10.1136/bcr.01.2011.3781.

• Quandt P, Puga M. Manic episode secondary to maca. Eur Psychiatry. 2016;33:S339. doi:10.1016/j.eurpsy.2016.01.1188.

• Brunetti P, Faro AFL, Tini A, Busardò FP, Carlier J. Pharmacology of herbal sexual enhancers: psychiatric/neurologic adverse effects review. Pharmaceuticals. 2020;13:309. doi:10.3390/ph13100309.

• Siwek M, Woroń J, Wrzosek A, et al. Adverse events of interactions between adaptogens and antidepressants: retrospective chart review. Front Pharmacol. 2023;14:1271776. doi:10.3389/fphar.2023.1271776.

• Posadzki P, Watson LK, Ernst E. Adverse effects of herbal medicines: overview of systematic reviews. Clin Med (Lond). 2013;13:7–12. doi:10.7861/clinmedicine.13-1-7.

Mechanism and Bioactive Constituents 

• Almukadi H, Wu H, Böhlke M, et al. Macamide is a time-dependent FAAH inhibitor. Mol Neurobiol.2013;48:333–339. doi:10.1007/s12035-013-8499-2.

• Alasmari M, Böhlke M, Kelley C, Maher T, Pino-Figueroa A. Inhibition of FAAH by macamides. Mol Neurobiol.2019;56:1770–1781. doi:10.1007/s12035-018-1115-8.

• Hajdu Z, Nicolussi S, Rau M, et al. Endocannabinoid system-modulating N-alkylamides from Lepidium meyenii. J Nat Prod. 2014;77:1663–1669. doi:10.1021/np500292g.

• Esparza E, Hadzich A, Kofer W, et al. Bioactive maca alkamides result from traditional postharvest drying. Phytochemistry. 2015;116:138–148. doi:10.1016/j.phytochem.2015.02.030.

• Cui B, Zheng BL, He K, Zheng QY. Imidazole alkaloids from maca. J Nat Prod. 2003;66:1101–1103. doi:10.1021/np030031i.

• Piacente S, Carbone V, Plaza A, et al. Tuber constituents of maca. J Agric Food Chem. 2002;50:5621–5625. doi:10.1021/jf020280x.

• Muhammad I, Zhao J, Dunbar DC, Khan IA. Constituents of maca. Phytochemistry. 2002;59:105–110. doi:10.1016/S0031-9422(01)00395-8.

• Ibrahim RM, Elmasry GF, Refaey RH, El-Shiekh RA. Maca roots: UPLC-HRMS + docking/dynamics. ACS Omega. 2022;7:17339–17357. doi:10.1021/acsomega.2c01342.

Phenotype/Processing, Identity, Metabolomics, and Quality Control Supporting 

• Zhao J, Avula B, Chan M, et al. Metabolomic differentiation of maca accessions using NMR/chemometrics. Planta Med. 2012;78:90–101. doi:10.1055/s-0031-1280117.

• Geng P, Sun J, Chen P, et al. Characterization of maca using mass spectral fingerprinting, metabolomics, and genetic sequencing. Planta Med. 2020;86:674–685. doi:10.1055/a-1161-0372.

• Chen J, Zhao Q, Liu Y, et al. Macamides in commercial products and postharvest effects. Int J Food Prop.2017;20:3112–3123. doi:10.1080/10942912.2016.1274905.

• Xia C, Deng J, Pan Y, et al. Profiling macamides/fatty acid derivatives across drying processes. ACS Omega.2021;6:24484–24492. doi:10.1021/acsomega.1c02926.

• Perez CJ, Conceição RS, Ifa DR. Chemical profiling of maca by TLC–DESI–MS. J Mass Spectrom.2021;56:e4690. doi:10.1002/jms.4690.

Supporting Context 

• Qaseem A, Snow V, Denberg TD, et al. ACP guideline: second-generation antidepressants. Ann Intern Med.2008;149:725–733.

• Gregorian RS, Golden KA, Bahce A, et al. Antidepressant-induced sexual dysfunction. Ann Pharmacother.2002;36:1577–1589.

• Kennedy SH, Rizvi S. Sexual dysfunction, depression, antidepressants. J Clin Psychopharmacol. 2009;29:157–164.

• Nurnberg HG, Hensley PL, Gelenberg AJ, et al. Sildenafil for antidepressant-associated sexual dysfunction. JAMA.2003;289:56–64.

• Nurnberg HG, Hensley PL, Heiman JR, et al. Sildenafil in women with antidepressant-associated sexual dysfunction. JAMA. 2008;300:395–404.
  (The rest of that long SSRI list is credible but redundant—keep only what you cite.)

• Clemesha CG, Thaker H, Samplaski MK. “Testosterone Boosting” supplements claims not supported by academic literature. World J Mens Health. 2020;38(1):115–122. doi:10.5534/wjmh.190043.

• Bambico FR, Gobbi G. CB1/anandamide as antidepressant targets. Expert Opin Ther Targets. 2008;12:1347–1366. doi:10.1517/14728222.12.11.1347.

• Shiah IS, Yatmah LN. GABA function in mood disorders review. Life Sci. 1998;63:1289–1303. doi:10.1016/S0024-3205(98)00241-0.