Shin D, Jeon SH, Piao J, et al. Efficacy and safety of maca (Lepidium meyenii) in patients with symptoms of late-onset hypogonadism: A randomized, double-blind, placebo-controlled clinical trial. [published online January 1, 2023]. World J Mens Health. doi: 10.5534/wjmh.220112.
Late-onset hypogonadism (LOH) in males is characterized by androgen deficiency and low testosterone levels with advancing age. Symptoms include decreased muscle and increased fat mass, anemia, osteoporosis, depression, low vitality, excessive sweating, hot flashes, low libido, and erectile dysfunction. LOH therapy focuses on testosterone replacement treatment (TRT), but there is no consensus on threshold levels of low testosterone, and LOH symptoms do not significantly correlate with total serum testosterone. TRT can raise risks of prostate cancer, heart attack, and stroke. Maca (Lepidium meyenii, Brassicaceae), a high-altitude plant of Peru, has been used since antiquity as food and medicine. Considered a "super food" for its nutritive and therapeutic qualities, maca research has focused on its ability to boost male libido without raising testosterone or causing serious adverse effects (AEs). The authors designed a randomized, double-blinded, placebo-controlled, clinical trial (RCT) to study the safety and efficacy of a novel gelatinized maca tablet in eugonadal patients with symptoms of LOH.
Eligible participants were males aged > 40 years, with a total score ≥ 27 on the Aging Males’ Symptoms scale (AMS). Exclusion criteria were prostate specific antigen (PSA) levels ≥ 4.0 μg/mL, history or diagnosis of prostate cancer, severe obstructive sleep apnea, serum total testosterone (TT) < 20 μg/mL in the morning, use of TRT < six months before randomization, untreated/unstable endocrine disorders, and liver enzymes or creatinine levels > 2.5 times normal limits. History or presence of mental, cardiovascular, cerebrovascular, or hematological disorders, or abnormal physical, hematological, or biochemical findings were also exclusionary.
Patients were recruited consecutively from February 2020 – February 2021 from among outpatients at Seoul St. Mary's Hospital (The Catholic University of Korea) and Guro Hospital (Korea University), both in Seoul, Republic of Korea. A total of 88 participants were evenly randomized to the maca or placebo group. The maca group took ~ 5 g/d maca (two 1000 mg tablets containing 833 mg gelatinized maca powder plus excipients before each of three meals); the placebo group, 6 g/d mixed lactose powder on the same dosing schedule. Compliance monitoring is not discussed. Maca and placebo tablets were made by Easter B&F (Seoul) at a Good Manufacturing Practices facility. Maca was standardized to contain n-benzyl-hexadecanamide 115-175 μg/g,* with minimal heavy metals and absent coliform bacteria.
Participants visited the outpatient department of urology at either hospital for follow-ups at four and 12 weeks. Primary outcome was changes in AMS total scores from baseline. Secondary outcomes were changes on questionnaires including Androgen Deficiency in Aging Males (ADAM), the International Index of Erectile Function (IIEF), and International Prostate Symptom Score (IPSS) as well as serum levels of TT, free testosterone (FT), and lipids, and weight and waist circumference (WC). Blood tests, urinalysis, vital signs, and AEs were used to monitor safety. Of the randomized patients, three from maca and five from placebo did not complete the RCT, leaving 80 at study's end; 41 in maca and 39, placebo. At baseline, there were significant differences between groups only in serum TT, FT, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), all higher in placebo vs. maca (P = 0.0086, 0.0018, 0.0181, and 0.0304, respectively).
AMS scores decreased significantly after four weeks for maca (P < 0.001) and placebo (P = 0.0251) but at 12 weeks were significantly improved only in the maca group (P < 0.0001). The improved in scores at 12 weeks over baseline was significantly greater for maca vs. placebo (P < 0.0001). In the maca group, ADAM scores fell from 70.7 to 29.3% positive after four weeks but rose somewhat after 12, to 56.1%. At 12 weeks, ADAM scores had improved significantly more with maca vs. placebo (P < 0.0001). IEFF scores improved significantly in the maca group at weeks four (P = 0.0241) and (P < 0.0001). Placebo IEFF scores worsened significantly at each data point. At 12 weeks, the change difference in IEFF scores significantly favored maca vs. placebo (P < 0.0001). Similarly, IPSS was significantly lower in the maca group at four (P = 0.0134) and 12 (P = 0.0025) weeks, and significantly better vs. placebo at study's end (P = 0.0001).
Although the placebo group showed decreased serum TT at 12 weeks vs. baseline, there were no significant between-group differences in TT or FT, nor in PSA. TC, high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels decreased with maca, but LDL-C increased. In placebo, TC, LDL-C, and TGs increased and HDL-C fell. Changes were not significant from baseline, but at 12 weeks, the decrease in TGs in the maca group was significantly different vs. placebo (P = 0.0047). Weight and WC increased in both groups but did not differ between them. Two patients in the maca group had mild gastrointestinal AEs that did not preclude continuing the RCT. There were no significant changes in laboratory tests or vital signs.
The authors suggest that further studies include long-term follow-up and examine mechanisms of action. They conclude that maca shows promise as an alternative to TRT. The authors declare no conflicts of interest.
*N-benzyl-hexadecanamide is a macamide, a group of non-polar, long-chain fatty acid N-benzylamides from maca with reported fertility-enhancing, aphrodisiac, immunomodulatory, hormone-regulating, hypoglycemic, antioxidant, memory-preserving, neuroprotective, cardioprotective, energizing, and anti-osteoporotic effects.