A Review of the Human Studies on the SA3X Spilanthes Extract.

Spilanthes is not likely an ingredient you’ve heard of, and fair enough too. Starting here I’ll explain my progression of interest, skip to the second title if you want to cut straight to the review of literature.

It was 2022 when I first encountered mention of Spilanthes. At the time I was just a survey of the libido landscape, seeing where we could continue to iterate and improve on what we had. With the timely release of our first iteration Nice Supplement Co. Tongkat Ali only weeks before Huberman discussed his use on Joe Rogan, we’d been lucky, and had a near exclusive market in New Zealand and many other countries. Sometimes it pays to be first. However Tongkat Ali has always displayed some drawbacks, namely the slightly shortened fuse that tends to make some of us a little… impulsive. So both selfishly, and thinking of a more refined iteration on our Tongkat Ali offering, Spilanthes is what caught my attention.

Most of the anecdotal reporting on Spilanthes at the time was what you expect from forums: “massive energy”, “massive erections”, “gaining heaps of muscle” and so on. Something about self reporting erectile function always gets a little exaggerated, either someone is a completely crushed limp-dick, or apparently the prize stud of the stable. Classic.

The state of available literature at that time was the first human populations study discussed below, and one rat study. The human population study is clearly of low data quality, so I moved on fairly quickly. The rat study was of more interest with results in significant LH, FSH, androgen, mounting frequency, and performance improvements. This was much like Fadogia and Bulbine that we’d found good anecdotal value in, but always keeping in mind the animal response for endogenous manipulation of hormones has been proven far easier to manipulate than humans.

Then the historical use of Spilanthes is what really drew me in. Spilanthes has had significant popularity in both male and female populations dating back as far as records, and in independent geographic regions which at the time of use would have had very little cultural cross over. The use of this plant as an aphrodisiac and wellbeing aid seems to have become popularized fairly independently in both South America and India, as well as some other tropical or sub-tropical regions where it grows wild. People coming to the same conclusions separate of each other? Always a good sign in my books.

A secondary line of interest was the other primary use of Spilanthes, for which it has also been commercialized in numerous ways this last few decades. Spilanthes has been found to yield a high concentration of a compound known as “Spilanthol”, also known as “Affinin”. First isolated in 1903, Spilanthol has demonstrated anesthetic properties via TRVP1 and TRPA1 channels, working in the signaling of sensation and pain. This is also likely associated with the tingling, some even say - electric-like feeling with topical applications. Hence the common names “electric daisy” and “ting flowers”, and “toothache plant”. In this use it has also demonstrated good anti-inflammatory related actions due to COX and LOX inhibition, and increasing skin permeability for other compound uptake which translates to its use in many skincare products now. Lines of research separate to libido mechanisms go quite deep and is a discussion for another day. But what it does provide is good insight into a safe range for human use, and with our population based outcomes and animal mechanistic success… a picture started to form.

Said picture then stagnated for over a year. Not having yet managed to source a quality trusted standalone extract, some tinkering with the Unbound Supplements “SAUCE” product which released with a Spilanthol standardized dose included. (SAUCE has since been superseded by a new formula: “TEST”). I attribute a lot of the unique feeling and value in that stack to the Spilanthes, however still hadn’t had the opportunity to test it as a standalone to be sure.

Fast forward to late 2023, I’m in the UK on the big Strom and Nice Supplement Co. “hey I’m a real person from New Zealand” tour. It was a usual Monday evening, sitting around the kitchen table. Richard was just back for his regular BJJ nights, amped up and going through the list of white belts he’d dominated. The full white belt yarns. But then he slips in, “Oh hey I’m working on a libido formula for Eddie Hall with Beast Pharm, what ingredients are you thinking?”. It was probably said in a more crass manner. Spilanthes was the first ingredient at mind. And just like that I had the excuse to dive deep on it again, leading us to here… Another whole year has passed. Any available literature has been scoured, and now growing some Spilanthes of my own for future R&D.

Beast Pharm “Big Love” released last month… and its perhaps the most ridiculously charged up, and quite frankly unmanageable libido formula I’ve experienced to date. What less could be fitting for The Beast himself? There’s plenty of videos online explaining Eddie’s experience with the stack. An important warning should be heeded, if you’re married, get your partner on it too… and just make good life choices. Reportedly Eddie’s third child was conceived during his beta testing of Big Love. My small role in this pleases me for whatever reason, take it for what you will. Spilanthes has had impact on the world, that’s for certain.

So while Spilanthes has an extensive history of traditional use, both animal and human investigations for libido functions are currently limited, and formal human studies only beginning after 2020. Of the three human investigations publicly available right now, all investigated the proprietary ingredient “SA3X” Spilanthes acmella standardized to 3.5% Spilanthol, and exclusively at the 500mg dose. All three were performed by the same third party research group, albeit with no clear association to the SA3X manufacturer “Stiriti Ayur Therapies Pvt. Ltd”, and who’s source of study funding was independent.

So without any further foreplay, the following is a summary of the three study's.

The first of the three investigations was performed on 240 healthy, regular 5-day a week training males, and of whom had purchased SA3X independently. There was no placebo group, being an open label population study. They were assessed via physical assessment and self questionnaire at: recruitment, 3 weeks in, and at the end of 2 months. The self reported outcomes on frequency of intercourse and erection period increased over the span of the check-ins. Self reported training duration and food intakes remained constant, while measures of muscle mass increased marginally.

While the investigators Pradhan et al. attributes this increased muscle mass benefit to potential testosterone modulation from the SA3X bioactive compound Spilanthol, also highlighted is an association with higher protein intake and increased muscle mass. The increases in mass are entirely within expected range of normal training adaptation, hence attribution to Spilanthol activity is fairly unfounded. While this study is only really of use as a pilot, the marketing material around SA3X, and in a “Nutritional Outlook” news release NutraShure has cited “performance benefits in the gym” and “muscle mass support” benefits of the ingredient. Citation used was to this population study - which is clearly poorly substantiated. Hypertrophy effects have not been investigated in the following trials.

It goes without explanation that self reported sexual intercourse frequency and duration is notoriously inaccurate. A more direct measure or placebo group for comparison, would be required in order to understand the contextual relevance of the outcome demonstrated in the study. This is what the next two trials investigate.

Ultimately, this first study is clearly of low quality and can really only be used as an indicator of customer self reported experience and satisfaction - which looks very positive. This appears to be the pilot study to determine if SA3X was worthy of further, more objective investigation, of which was performed in the following two trials.

In this second study, Pradhan et al. directly investigate the use of 500mg SA3X daily for 30 days, in a intention-to-treat male population of 448 patients, aged between 18 and 45, with mean ages in the early 30’s. The men were suffering from self reported erectile dysfunction (ED) but not taking other ED medications. Intervention to placebo ratio was 1:1, with the remaining third included in the observational cohort. The primary outcome measure was the standard Men's Sexual Health Questionnaire (MSHQ), which is a clinically validated 25-item self-administered questionnaire acknowledge as as standard internationally. The secondary outcome was self reported erection duration and total score on the International Index of Erectile Function (IIEF) total score, a 15-question validated, self-administered questionnaire also with validated use in clinical settings relating to ED

Outcomes can be seen as below, showing clear clinical and statistical significance in the SA3X intervention group. Note the benefit was maintained in the SA3X group at the one-month post intervention time point, indicating sustained improvement of outcomes. For reference, a total MSHQ score in the range of 28 and above represents good ejaculatory function, scores of 22-27 represent average ejaculatory function, and a score <22 is used to diagnose ejaculatory dysfunction. Mean baseline score before intervention was 20.11.

This second study is the first documented RCT on Spilanthes for use in ED and the sexual performance and ED category on the whole. The correcting of the SA3X intervention group ED symptoms is self evident, both statistically, but also clinically for patient wellbeing and quality of life. Final mean MSHQ score was 37.35. Noting this extends well into the above average MSHQ score range of 22-28, and so merits extra attention. Extrapolation to healthy average populations looking for above average libido and erectile performance may consider this potentially meaningful for their goals, and worth investigation at the very least.

This second study provides a fairly conclusive performance outcome for men with erectile issues, and indicates cause for interest in healthy normal populations. However causality has not yet been determined, and concluding that this is a testosterone mediated outcome would be an unfounded leap.

Given the relationship between normal healthy range testosterone and erectile function, this third study in the series makes the logical step to evaluating serum changes in hormonal profile. Again, the study population was a sizeable number, featuring 326 males, age 25-60. All patients had self diagnosed ED and are part of an intention to treat group. The baseline assessment included an physical mass and serum testosterone test. Participants responded to the International Index of Erectile Function (IIEF), as well as an estimate of ability to maintain erection duration. All patients received the 500mg SA3X intervention for three months with no placebo or observation group, but were divided into two groups for those with serum testosterone above 300ng/ml, and those below.

Outcomes are as below, showing statistically significant improvements in serum testosterone levels, however only to a minor degree (>10%) that may not be considered clinically significant.

Considering the context of the study, the minor shift, and number of other potential lifestyle variables that can modulate testosterone, the following conclusion from the authors is particularly relevant.

That would be putting it mildly, but you get the point.

In the first study an open population approach was taken, presumably as a pilot to determine value before instigating the following two investigations. Due to the low quality of measures from this study and lack of reference group, the only real conclusion that can be drawn is how the SA3X users are reporting outcomes after use. Not necessarily reflective of true outcomes. This did display a positive trend for libido, with reporting of meaningfully better sexual performance. The second measure of physical characteristics showed an improvement, but considering the population was a regular training group, the improvements don’t appear meaningful to the SA3X intervention.

In the second study, a self reported ED population was the group for intervention, and a strong study design with triple blinding, and an observation population was implemented. The outcomes were especially impressive, with the SA3X intervention bringing a sustained increase in MSHQ and IIEF scores from below average to well above average ranges. This implies that SA3X may have value to average performing persons who want to improve their sexual functions and satisfaction also. However causality is not established.

In the third study, again a ED population was recruited for use with the same 500mg SA3X dose, however no placebo or observation group was implemented. They were studied for changes in total testosterone levels, in which a statistically significant, but not clinically significant increase was seen. Adding confounding factors such as use of other medications that may alter serum testosterone also reduced the efficacy of this measure, and further, better controlled research would be demanded to draw useful conclusions on total testosterone. Of particular value would have been measures of SHBG to determine any changes in free testosterone, estrogen, or dihydrotestosterone levels - which may have undergone greater shifts that would better correlate with the meaningful improvements in libido and sexual performance demonstrated in the second study. Another basic measure would have been continuing with the same MSHQ in this third study to confirm reliability of outcomes, or indicate to differences in study setup - such as a differing SA3X batch.

The strength in all studies was the number of participants, and extended duration of study. The weaknesses was the poor ability to control external factors such as medications and lifestyle, however this is an accurate reflection to real world conditions in which SA3X would be used as an open population supplement. The other key weakness was the limited study geography, in all three being limited to males from the Hyderabad, India area.

Also key to acknowledge was from the very first study, and showing clearly through in the mild discussion presented in the third, the investigators do seem to favor the SA3X ingredient beyond that in the evidence presented. The studies were all performed with proper registration and oversight to maintain standards, and no clear financial or other relationship is evident with the SA3X manufacturers. However there appears to be reason for caution around their biased interpretation of results.

SA3X and 500mg daily does appear to be a worthwhile libido and sexual performance enhancer for both males with ED and potentially even average functioning looking for above average outcomes (as measured by MSHQ scores). However the mechanism of action is not yet demonstrated to be associated with total testosterone, and many other potential mechanisms of action have not yet been investigated. Further insight into range of dose response would be valuable.

Is SA3X the only extract that will yield these results? I don’t expect so. While there is value in the known Spilanthol standardisation of SA3X, and ability to reference studies with this specific extract, really any decent Spilanthol yielding extract should do the job. For example, the Beast Pharm Big Love is a simple 10:1 extract, the Unbound Supplements SAUCE replacement (known as “TEST”) also uses a simple ratio extract.

Am I fan of Spilanthes, based off the research available? Yes. Personal experience further supporting it.

You can look forward to seeing both Spilanthes and Spilanthol in formulation for future products I get involved in.

This discussion is to come. Watch this space.

Spilanthes acmella has a a particularly distinctive appearance:

• A low-growing herb, typically reaching heights up to 45 cm.

• The leaves are oval-shaped, dark green, and with serrated edges.

• Its most notable feature is the flower head, which is cone-shaped, usually yellow or red-orange in color, often with a darker center.

• Generally growing in a spreading or trailing manner, forming small bushes or ground cover.

Spilanthol is an alkamide compound with the following material characteristics:

• Physical state: Oily liquid at room temperature

• Color: Light yellow

• Melting point: 23 °C (73.4 °F)

• Boiling point: 165 °C (329 °F)

• Solubility: Poorly soluble in water, but soluble in organic solvents

• Molecular formula: C14H23NO

• Molecular weight: 221.34 g/mol

[1] Evaluation of effects of Spilanthes acmella extract on muscle mass and sexual potency in males: a population-based study (Pradhan - Patnaik, 2021)

[2] Randomized, Triple-Blinded, Placebo-Controlled Trial of SA3X (Spilanthes acmella) for the Management of Erectile Dysfunction (Patnaik - Pradhan, 2022)

[3] Evaluation of Serum Testosterone Levels Following Three Months of SA3X (Spilanthes acmella) Supplementation (Patnaik - Pradhan, 2022)

[4] An Interview with Prabhu Ramachandran of Stiriti Ayur Therapies Pvt Ltd (2017)

[5] NutraShure to introduce and distribute SA3X to U.S. market (2023)

[6] Male sexual health questionnaire (MSHQ): Scale development and psychometric validation (2004)

This content is for educational purposes only and does not intend to cure or diagnose disease, nor make any health claims. There is no intent to slander in any way, but rather produce an informed and accurate third party perspective on the product. Always consult your accredited medical professional before introducing a new supplement. This content is not to be copied or repurposed in any form without express permission from the author.

This article was written for and first published to stromsports.co.nz on 15.10.2024