There have been few choices for women that increase sexual desire, until now . . .

Maca Lifts
Libido’s Veil

Selective serotonin reuptake inhibitors have
undesirable side effects that maca can alleviate
By Will Block

O

ne of the major side effects that accompanies the use of SSRI (serotonin selective reuptake inhibitors) antidepressants is the fading of sexual desire, the loss of libido. In one recent study in which 1473 subjects were treated openly with the SSRI citalopram for up to 14 weeks, 54% reported decreased libido—59% of whom were women—and 36% reported difficulty achieving orgasm—48% of whom were women.1 Also, 37% of the men reported erectile dysfunction. From these results, we can see that women tend to have more libido problems than men, and other studies bear this out. But men have their sexuality problems too, and they span the gamut.

A Dilemma in Search of a Solution

However, as women are painfully aware, there has been at lot of disparity regarding solutions to their sexual problems, with men having garnered the lion’s share of prosexual drugs and nutrients. It’s a crying shame! The core truth is that antidepressant-induced sexual dysfunction continues to be a big issue in the treatment of women with depressive disorders, who may outnumber men 2 to 1. Up to 50% of patients who receive pharmacological treatment report sexual dysfunction. Indeed, the antisexual side effects of SSRIs have become so distressing to some patients that they can lead to discontinuing treatment, even though these SSRIs are efficacious for depression.* Moreover, the dilemma is compounded due to the high cost of treatment. Thus, many have begun to look at complementary and natural treatments, and the possibility that there may be hope in these areas to improve sexual functioning.


* 5-HTP or tryptophan nutritional formulations do not appear to have as much of an antisexual downside. This makes sense, owing in part to a recent report showing that SSRI exposure induces single nucleotide polymorphisms in glutamatergic genes, which were associated with decreased libido, while this was not the case for serotonergic genes.1 Also see sidebar, “Targeting the Glutamatergic System.”


Targeting the Glutamatergic System

Despite presumptions to the contrary, SSRIs do not exert their negative effects on sexual function through the serotonergic system, but instead through the glutamatergic system. So targeting the glutamatergic system might prove to be a successful strategy for the treatment of sexual dysfunction in individuals who take SSRIs to cope with depression. Dr. Roy Perlis and colleagues at Massachusetts General Hospital in Boston* ran an interesting experiment in which they measured the antisexual effects of SSRIs on genetic predictors.1 “While there was little evidence of association with sexual dysfunction for serotonergic genes, there was intriguing support for the involvement of a number of genes related to glutamatergic neurotransmission,” states Perlis.2


* Incidentally, Massachusetts General Hospital is also where maca research investigating the ability of the Peruvian herb to compensate for the negative side effects of SSRIs has taken place (see the main story, “Maca Lifts Libido’s Veil”).


Perlis et al. analyzed genetic data from 1,473 Causcasian patients treated with the SSRI citalopram (at levels as high as 60 mg/day) for major depressive disorder, but who were not psychotic, for a period extending as long as 14 weeks. Most significantly, 36% experienced difficulty with orgasm and 54% reported decreased libido (59% of whom were women). Of the 574 men in the study, 37% suffered erectile dysfunction. Upon analyzing the relationship between these symptoms and select single nucleotide polymorphisms from genes thought to be involved in antidepressant mechanisms, what they found was surprising. Components of the glutamatergic system’s implicated genes, when examined, were associated with sexual dysfunction: one with erectile dysfunction (GRIN3A), two with loss of libido (GRIA3 and GRIK2), and one with difficulty achieving orgasm (GRIA1). No implicated genes in the serotonergic system were associated with sexual dysfunction!

The researchers, by repeating their analysis in other patient cohorts, hope to learn more, and the good news is that at last there appears to be a target.

  1. Perlis RH, Laje G, Smoller JW, Fava M, Rush AJ, McMahon FJ. Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology 2009 Jun;34(7):1819-28.
  2. Payton S. Sexual dysfunction: Glutamatergic system mediates sexual side effects of SSRIs. Nat Rev Urol August 2009;6:405. doi:10.1038/nrurol.2009.136.

Maca Anecdotes and New Studies

Enter the plant maca (Lepidium meyenii), the root of which has been discovered to have fertility-enhancing properties, first reported in 1961 when it was found to increase fertility in rats.2 In Peru, both men and women have known about this aspect of maca for a long time and they have traditionally increased their dietary intakes of maca when planning to conceive. Local usage has encompassed both nutritional and medicinal purposes. Following the first study, there have been numerous others in animals demonstrating spermatogenic effects and prosexual use. Also, there has been significant anecdotal evidence from South America lending support for the use of maca to alleviate sexual dysfunction, and even to enhance sexual function. Known as “Peruvian Ginseng,” maca is a hardy perennial plant found to grow wild at high altitudes in the Andean Mountains. Shockingly, it was recently listed as an endangered species. However, due to widening awareness of its prosexual potential, it is now widely cultivated.


In one recent study in which
1473 subjects were treated openly
with the SSRI citalopram,
54% reported decreased libido
—59% of whom were women.


Maca root shares certain characteristics with cabbage, cauliflower, and broccoli, the family of which contains the biochemicals called glucosinolates or mustard oil glucosides. These can be converted in the body into a substance that can inhibit certain kinds of cancer in animals. Furthermore, among its array of interesting compounds, maca also contains uridine and malic acid.* Studies have shown that maca is able to improve aspects of sexuality, but not due to any effect directly on serum hormone levels. Rather, maca may affect the receptors that these hormones bind to, and consequently affect the body through these hormones, and in both sexes, as we shall find out.


* Dry maca hypocotyls (a part of a germinating seedling) contain 59% carbohydrates, 10% proteins (including most of the essential amino acids), 8.5% fiber and 2.2% lipids. They purportedly also contain significant levels of iodine, which may explain the Peruvian high plateaus’s absence of the goiter often found in other remote, high-mountain regions of the world. Maca also contains a high concentration of aromatic glucosinolates—benzyl and p-methoxybenzyl glucosinolate in particular—and their derived isothiocyanates (also found in the mustard oil). These are the same anticancer compounds found in other cruciferous vegetables like broccoli and cabbage. Also found in Maca are antioxidant flavanols, including catechin, epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate. Maca also contains sterols, such as campesterol, stigmasterol and beta-sitosterol, and alkamide compounds similar to those found in Echinacea spp.


Male Libido Effects

Nonetheless, there have been only a few clinical trials to support maca claims. In 2002, a 12-week double-blind, placebo-controlled, randomized, parallel trial in which active treatment with different doses of gelatinized maca was compared with placebo.3 The aim was to investigate whether maca could affect sexual desire by altering mood or serum testosterone levels. The subjects (aged 21–56), 57 males, received one of two doses, either 1,500 or 3,000 mg/day, or placebo. Depression and anxiety levels were measured throughout the trials with no discernable differences. Improvement in male libido was found in 40% of the subjects taking maca from 8 weeks onward. The 1,500 mg dose appeared to be as effective as the 3,000 mg dose. Hormonal levels were not altered. However, there were statistical flaws in the trial which weaken the results.


† Gelatinized Maca root is not an extract. Instead, gelatinization is a process whereby Maca root is pre-cooked and dried in a manner similar to the manufacture of instant noodles. Peruvian Indians never consume raw maca, but instead, always cook it.


In another study, 9 healthy men (aged 24–44) were followed for a four-month period to determine the effect of gelatinized maca on sperm production and motility.4 Given maca at either 1,500 or 3,000 mg/day, seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility were found to increase over the course of the investigation. As with the early study, hormones which produce such effects in the body remained unchanged. Yet the trial was not randomized, and thus the results may be distorted.

Finally, Studies with Women

More recently, a study with 14 postmenopausal women has shown that maca at 3,500 mg/day for 6 weeks, compared with placebo for the same length of time, crossed over for another 6 weeks (when the test material and placebo were switched), reduced psychological symptoms, including anxiety and depression. It also lowered measures of sexual dysfunction in postmenopausal women independent of estrogenic and androgenic activity.5


Maca reduces psychological symptoms,
including anxiety and depression,
and lowers measures of sexual
dysfunction in postmenopausal
women independent of
estrogenic and androgenic activity.


Another recent study, conducted at the venerable Massachusetts General Hospital, Boston by Christina M. Dording, MD and colleagues, investigated whether maca could be beneficial for subjects suffering SSRI-induced sexual dysfunction.6 Using a double-blind, randomized, and parallel dose-finding design, the researchers also sought to determine the effects in 20 outpatients with regressed depression, consisting of 17 women and 3 men (aged 23–49). The study compared two maca regimens: one providing 1,500 mg/day and the other 3,000 mg/day. Lasting for just 4 weeks, 10 subjects completed the study, and 16 subjects (7 on 1,500 mg/day and 9 on 3,000 mg/day) were found eligible for intent-to-treat analyses§ on the basis of having had at least one post-baseline visit. Discontinuation reasons include: change of relationship; inability to keep study appointments; change in antidepressants; negative response to the smell of maca; and personal reasons. To the best of the researchers’ knowledge, tolerability issues were not a reason for discontinuing the trial.


‡ Subjects with major depressive disorder admitted to the study had to be in remission (<10 on the 17-item Hamilton Rating Scale for Depression). Also required, the subjects had to be without significant anxiety symptoms (<10 on the Hamilton Rating Scale for Anxiety).

§ An intention to treat is an analysis based on the initial treatment intent, and not on the treatment eventually administered. It is intended to avoid misleading artifacts that can spring up in intervention research. As an example, people who have a more intractable problem tend to drop out more rapidly, and even a treatment that is completely ineffective may appear to be providing benefits. Especially if one merely compares the condition before and after the treatment for only those who finish the treatment (ignoring those who were enrolled originally, but have since been excluded or dropped out). From this viewpoint, everyone who begins a regimen is considered to be part of the trial, whether they finish it or not.


Significant Libido Improvement

Intent-to-treat subjects using the 3,000 mg/day dose of maca had a significant improvement by both measurement gauges used, the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). However, subjects using the 1,500 mg/day dose of maca showed no benefit. Importantly, libido improved significantly for both the intent-to-treat group and the completion group based on ASEX item #1 (for measuring libido), but only for the 3,000 mg/day dose. The conclusions drawn were that maca may enhance libido, ease SSRI-induced sexual dysfunction, and that its effects may be dose-related.

Sexual Dysfunction Selection Criteria

There was a wide variety of SSRIs used by the subjects, 8 different ones, and 9 subjects also used other psychotropic drugs. Many psychotropic drugs can also cause sexual dysfunction. To be selected for the trial, potential subjects were required to experience 1 or more of the following for at least 4 weeks: (1) failure to have an orgasm during sexual activity, (2) significant orgasm delay with either masturbation or intercourse, (3) inability to achieve or maintain an adequate erection until completion of sexual activity or for women, insufficient lubrication-swelling response resulting from sexual excitement, or (4) reduced libido.


Libido improved significantly for
both the intent-to-treat group and
the completion group based on
ASEX item #1 (for measuring libido),
but only for the 3,000 mg/d dose.


Also significant, the subjects had no sexual dysfunction prior to taking the antidepressant, indicating that there was a clear causal relationship between the sexual dysfunction and the antidepressant treatment. In addition to assessing the subjects every 2 weeks with ASEX and MGH-SFQ tests, diary entries by each subject tracked sexual successes and disappointments. During the course of the study, 4 people left after the screen visit. Thus, 16 subjects (14 women, 2 men, split into 9 high-dose and 7 low-dose) were accepted for intention-to-treat analysis by finishing at least 1 study visit after medication began. Throughout the study, the depressive and anxious symptoms of subjects remained stable, with the exception that the intent-to-treat sub-group taking the higher level of maca was found to experience a significant decrease in depression. This improvement could either be a direct effect of maca or perhaps a manifestation of increased sexual satisfaction.


The intent-to-treat sub-group
taking the higher level of maca
was found to experience a
significant decrease in depression.


Maca is Safe and Less Costly

Maca was well-tolerated overall. There was no evidence of adverse reactions with maca. Maca has been reported to have a low degree of acute oral toxicity in animals and low cellular toxicity in vitro. Given its benign side-effect profile, maca may be used by cardiac-impaired or elderly populations taking oral nitrates who may not be eligible for sildenafil or other phophodiesterase inhibitors. Furthermore, maca is significantly less costly than these drugs. Patients with thyroid conditions should avoid maca because glucosinolates taken in excess and combined with a low-iodine diet can cause goiter. In animals studies, no adverse reactions were reported with rats fed maca extract in doses up to 5 g/kg in one study. Its long-time use as a food product suggests low potential for toxicity.


Despite the significant
armamentarium of prosexual
products for men, there have been
few for women, until now.


Robust and Statistically Significant Improvements in Women

Once again, the most significant findings in the Dording et al. study were the notable improvements in sexual function, along with the most robust and statistically significant improvements observed in those women receiving the highest dose of maca, 3,000 mg/day. Despite the significant armamentarium of prosexual products for men, there have been few for women, until now. So beneficial are the findings of maca for women—despite the study’s small size and the lack of a placebo arm—that the outcome can be seen as an important step in the management of induced-antidepressants sexual dysfunction . . . and a new opening for further research.

References

  1. Perlis RH, Laje G, Smoller JW, Fava M, Rush AJ, McMahon FJ. Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology 2009 Jun;34(7):1819-28.
  2. Chacon RC. A study of the chemical composition of Lepidium meyenii. Dissertation, Univ Nac Mayor de San Marcos, Peru, 1961.
  3. Gonzales GF, Cordova A, Vega K, Chung A, Villena A, Gonez C et al. Effect of Lepidium meyenii (Maca) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia 2002;34:367-72.
  4. Gonzales GF, Cordova A, Gonzales C, Chung A, Vega K, Villena A. Lepidium meyenii (Maca) improved semen parameters in adult men. Asian J Androl 2001;3:301-3.
  5. Brooks NA, Wilcox G, Walker KZ, Ashton JF, Cox MB, Stojanovska L. Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content. Menopause 2008 Nov-Dec;15(6):1157-62.
  6. Dording CM, Fisher L, Papakostas G, Farabaugh A, Sonawalla S, Fava M, Mischoulon D. A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction. CNS Neurosci Ther. 2008 Fall;14(3):182-91.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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