Saw palmetto also known as Serenoa repens, American dwarf palm tree, cabbage palm or Sabal serrulatum, is a botanical extract with antiandrogenic properties from the berries of the Serenoa repens dwarf tree, native to the subtropical Florida and the Southeast United States 1). Saw palmetto has gained commercial popularity for its purported benefits on hair regrowth 2). Saw palmetto is a competitive, nonselective inhibitor of both 5α-reductase isoforms, blocking nuclear uptake of dihydrotestosterone (DHT) and decreasing DHT binding capacity to androgen receptors by nearly 50% 3). Saw palmetto also increases the activity of 3α-hydroxysteroid-dehydrogenase, an enzyme converting DHT to its weaker metabolite, androstanediol 4). Due to its antiandrogenic effects, Saw palmetto has been used as an alternative treatment for benign prostatic hyperplasia (BPH) 5), dating back to the 15th century BCE, Egypt 6). However, also worth noting are the opposite views regarding Saw palmetto’s actual effect on androgen-dependent parameters 7) and debatable clinical efficacy in treating benign prostatic hyperplasia (BPH) 8).
Saw palmetto’s antiandrogenic properties, minimal side-effect profile 9) and low drug interaction potential have prompted its use as a complementary hair loss (alopecia) remedy 10). Saw palmetto extract has been evaluated for the treatment of male and female pattern hair loss (androgenetic alopecia) 11), telogen effluvium (temporary hair loss due to the excessive shedding of resting or telogen hair after some shock to the system) 12), seborrheic dermatitis 13) and facial sebum 14), as a monotherapy or in combination with other supplements, in oral and topical formulations.
Saw palmetto extract can be prepared as liquid via hot water or supercritical elicitation with carbon dioxide, or as powder via mechanical grinding of Serenoa repens raw berries 15). Saw palmetto extract is primarily comprised of fatty acids (70–95%) 16), phytosterols such as beta-sitosterol (0.1%) 17), beta-carotene, vitamin E derivatives, and polysaccharides; however, the exact ratios can vary depending on the specific preparation 18). Saw palmetto’s fatty acid components directly inhibit 5-alpha-reductase enzyme (also known as DHT blocker) activity and the conversion of testosterone to dihydrotesterone (DHT) 19), aid in the 5-alpha-reductase enzyme’s selective hormone transformation processes 20) and influence access to cofactors by affecting the enzyme’s conformational state 21). Existing Saw palmetto (Serenoa repens) ingredients show lauric acid, myristic acid, and oleic acid may be the main fatty acids responsible for the inhibition of 5-alpha-reductase 22).
Information on the safety of saw palmetto comes primarily from studies of its use for BPH and treatment of urinary symptoms in men 23). Little is known about the safety or side effects of saw palmetto when used for other conditions, especially in women or children. Saw palmetto may be unsafe for use during pregnancy or while breastfeeding 24). At the present time, the weight of scientific evidence suggests that consumption of Saw palmetto poses a risk to unborn male fetuses. Inhibitors of 5-alpha-reductase are known to cause adverse effects and are thus contraindicated in women who may become pregnant. They are classified as pregnancy category X, the category indicating the greatest concern for pregnant women. The pregnancy category X of these drugs results from teratogenicity studies in animals. These studies have shown that male offspring of animals (including monkeys) that consumed 5-α-reductase inhibitors exhibit abnormal male genitalia development.
Table 1. Saw palmetto extract composition of fatty acids and phytosterols
|Content in Saw palmetto extract||Proportion for each category|
|Fatty acids (40–80%)||Oleic acid||> 30%|
|Stearic acid||< 5%|
|Phytosterols (< 1%)||β-Sitosterol||80.00%|
Footnotes: Saw palmetto extract is a mixture of various compounds. The percentage of the nine different single fatty acids (capric acid, caprylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid) was similar in products prepared by a similar extraction method 25). Saw palmetto fruits contained high amounts of oleic acid as well as lauric acid and each fatty acid was comprised approximately 30–40% of the total fatty acids 26). Oleic acid and lauric acid were also the predominant fatty acids irrespective of supplement types of liquid, powder, dried berry, or tincture (Penugonda and Lindshield, 2013). β-Sitosterol was the most abundant phytosterol, although phytosterol content varied in different supplement types 27). One of the main difficulties in assessing the efficacy of Saw palmetto extract is the absence of standardization in composition 28), which may result in varying efficacy of Saw palmetto extract in BPH treatment. Therefore, a standard formulation is essential to ensure a consistent biological effect of Saw palmetto extract. Permixon, the n-hexane lipidosterolic extract of Saw palmetto, is the most studied form of Saw palmetto extract and studies with Permixon have produced relatively consistent beneficial effects on lower urinary tract symptoms associated with benign prostatic hyperplasia at preclinical and clinical levels.[Sources 29), 30) ]
Saw Palmetto uses
Historically, Saw palmetto was used for a variety of conditions, including disorders of the male and female reproductive organs and coughs due to various diseases. Native Americans used Saw palmetto fruit both as a food as well as an herbal remedy with multiple uses, including as a sedative, diuretic, sleeping aid, expectorant and cough suppressant, aid to lactation, infertility, indigestion and urinary problems 31). Currently, Saw palmetto is promoted as a dietary supplement for urinary symptoms associated with an enlarged prostate gland also called benign prostatic hyperplasia (BPH), as well as for chronic pelvic pain, migraine, hair loss, and other conditions. Many studies have evaluated various preparations of Saw palmetto for lower urinary tract symptoms associated with prostate enlargement (BPH) in men 32). One-year follow-up Saw Palmetto for Treatment of Enlarged Prostates (STEP) study 33) and 18-months follow-up Complementary and Alternative Medicine for Urological Symptoms (CAMUS) study 34) have showed that Saw palmetto did not demonstrate superiority over placebo in men with BPH who had lower urinary tract symptoms. Moreover, a prospective, 1-year trial using saw palmetto versus finasteride in the treatment of category III prostatitis showed that patients treated with saw palmetto had no appreciable long-term improvement 35). There isn’t enough research on Saw palmetto for conditions other than BPH to allow any conclusions to be reached. In terms of Saw palmetto for hair loss, although robust clinical efficacy data are lacking, saw palmetto extract in either topical or oral formulations may have a role in the treatment of hair loss disorders such as androgenetic alopecia or telogen effluvium, demonstrating modest improvement in hair regrowth 36). However, as many of the current clinical trials are lacking in quality (descriptive, qualitative measures, small sample sizes, inadequate product content description, long-term results, etc.), the majority of outcomes should be interpreted with caution. Additionally, it is worth emphasizing that in the only head-to-head trial conducted between Saw palmetto and finasteride (Proscar, an 5-alpha-reductase blocker also known as DHT blocker), it was Saw palmetto that demonstrated inferiority. Further independent and high-quality randomized controlled trials are necessary in order to better delineate the efficacy of Saw palmetto in male and female pattern hair loss (androgenetic alopecia) and long-term adverse events.
Saw palmetto for enlarged prostate gland
Testosterone is converted in prostatic cells to dihydrotestosterone (DHT), catalyzed by the enzyme steroid 5-alpha-reductase. DHT binds to androgen receptors in the nucleus of prostate cells, stimulating cellular growth and division 37). In benign prostatic hyperplasia (BPH) tissue, 5-alpha-reductase levels are higher than in tissue not affected by BPH 38). The presence of DHT may also stimulate 5-alpha-reductase activity, causing a positive feed-back loop, and more DHT 39). The standardized liposterolic Saw palmetto extract has been found to be a potent inhibitor of 5-alpha-reductase, resulting in decreased tissue DHT. Serenoa repens also competitively inhibits binding of testosterone and DHT to cytosolic and nuclear androgen receptors 40).
Despite numerous reports regarding Saw palmetto’s clinical efficacy, comprehensive meta-analyses have failed to demonstrate significant improvement in BPH symptoms or objective BPH disease parameters, thus casting doubt on Saw palmetto’s previously attributed antiandrogenic properties 41), 42). Two large, high-quality studies funded by the National Institutes of Health, each using a different preparation of saw palmetto, found it was no more effective than a placebo (an inactive substance) for BPH symptoms 43), 44). Some studies of Saw palmetto products other than those used in the National Institutes of Health-sponsored studies have suggested that they might be helpful for BPH symptoms, but many of these studies were of low quality 45), 46).
In a 2011 randomized, double-blind, placebo-controlled clinical trial 47) involving 369 men age 45 years or older with symptoms of BPH. The men took either Saw palmetto (at daily doses that increased during the study from 320 milligrams (mg) to 640 mg and finally 960 mg) or a placebo for 72 weeks. At the end of the study, the men who had taken saw palmetto had no greater improvement in urinary symptoms associated with BPH than those taking the placebo 48). In addition, a 2009 Cochrane review of nine trials concluded that saw palmetto has not been shown to be more effective than placebo for this use.
A 2012 Cochrane review of 32 randomized controlled trials involving 5,666 men with BPH found that Serenoa repens, at two and three times the usual dose, provides no improvement in urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH 49).
A 2014 randomized trial of 225 men with lower urinary tract symptoms and BPH examined the efficacy and tolerability of combination therapy between saw palmetto, lycopene, and selenium plus tamsulosin versus single therapies 50). The findings suggest that a combination therapy of Saw palmetto, lycopene, selenium, and tamsulosin is more effective than single therapies in improving International Prostate Symptom Score and increasing maximum urinary flow rate 51). It was noted that after 6 months of treatment, the combination therapy significantly improved symptom scores compared with single therapy, and from 6 to 12 months, combination therapy demonstrated significant improvement in urine flow rate compared to tamsulosin alone. There were no reported treatment-related adverse events associated with combination therapy.
A 2018 phase IV, non-inferiority, open-label, clinical trial (SPRITE study) of 404 participants found that treatment with saw palmetto, selenium, plus lycopene was not inferior to tadalafil 5 mg for improving the International Prostate Symptom Score and maximum urinary flow rate in men with lower urinary tract symptoms 52).
This 2020 systematic review and meta-analysis of randomized, double-blind, controlled trials (involving 1,080 patients [543 in the Serenoa repens group and 537 in the tamsulosin group]) indicated that Saw palmetto had the same effect in treating BPH compared with tamsulosin (a selective a1-adrenaline receptor blocker) in terms of International Prostate Symptom Score (IPSS), quality of life and postvoid residual volume after at least 6-month treatment cycle, however, tamsulosin had a greater improvement in postvoid volume compared with Saw palmetto 53). And Saw palmetto did not increase the risk of adverse events especially with respect to ejaculation disorders and libido decrease 54).
Saw palmetto for hair loss
Clinical evidence regarding the efficacy of Saw palmetto-containing products to treat hair loss is limited. Saw palmetto has shown promising results in mice models, with hair regrowth mediated through transforming growth factor-β (TGF-β) and mitochondrial signaling pathways 55). Additionally, in vitro (test tube) models have demonstrated Saw palmetto’s ability to inhibit inflammatory gene expression in human keratinocytes, suggesting a multifaceted mechanism for the treatment of androgenetic alopecia, in addition to its proposed antiandrogenic properties 56). The mechanism in which Saw palmetto instigates hair growth in telogen effluvium is not entirely clear. A possible explanation may be secondary to its anti-inflammatory properties, or to beta-sitosterol’s purported angiogenic effects, stimulating vascular endothelial growth factor in vitro and promoting neovascularization in vivo 57).
Several human studies have demonstrated modest hair regrowth using oral and topical Saw palmetto-containing products among patients with androgenetic alopecia, female-pattern hair loss, telogen effluvium and self-perceived hair thinning 58). Improvement in total hair count ranging from 3.4 to 27% 59), increased hair density in up to 83.3% of patients 60), 60% improvement in overall hair quality 61) and stabilized disease progression among 52% of patients 62) were noted with use of various Saw palmetto-containing oral supplements, topical lotions, and/or serums.
However, almost all current formulations containing Saw palmetto also contain other vitamins, minerals, or chemical additives, making it challenging to discern the exact extent of Saw palmetto’s contribution to the observed clinical findings. Additionally, among the randomized controlled trials presented there were several methodological flaws, such as inadequate statistical analyses 63), limited sample size 64), lack of appropriate comparison groups 65), qualitative rather than quantitative measures of hair regrowth 66) and conflicts of interest with sponsorship by the pharmaceutical industry 67). In the only head-to-head randomized controlled trial comparing Saw palmetto-containing tablets to systemic finasteride, moderate efficacy in hair regrowth was demonstrated among the Saw palmetto group; however, overall outcomes were inferior to finasteride 68). Clinical trials involving patients with telogen effluvium were only conducted using female patients, and results were described qualitatively. Currently, there is a trial (NCT03052413) assessing the efficacy of an Saw palmetto-containing supplement in women with mild to moderate hair loss; however, results are pending.
The first randomized controlled trial tested the efficacy of a topical Saw palmetto-containing lotion twice daily, alone and in combination with an oral tablet containing gelatin-cystine 4 times a day, in 60 men and women with androgenetic alopecia over a period of 50 weeks 69). Five arms were studied with varying combinations of lotion and oral agent versus vehicle and placebo. Hair samples were degreased, dried, counted on a grid, and weighed in an analytical balance at 22°C. The Saw palmetto-containing topical demonstrated a time-dependent mean increase in hair count of 17% by week 10 and 27% by week 50, as compared to 6 and 14% among the vehicle group at weeks 10 and 50, respectively 70). Hair mass and caliber increased approximately 20% by week 10 from baseline and 30% by week 50 using topical Saw palmetto (p < 0.005), versus an approximately 10% decrease and an 8% increase amongst the vehicle group at weeks 10 and 50, respectively. The use of topical Saw palmetto and oral gelatin-cystine supplement caused a further increase of approximately 50% in all hair growth parameters when compared to use of either agent alone. Both topical Saw palmetto and gelatin-cystine supplement were well tolerated, and no adverse events were reported 71).
A small randomized controlled trial evaluated the efficacy of an oral tablet containing 200 mg of Saw palmetto extract and an extra 50 mg of beta-sitosterol (which has also been studied singularly for its antiandrogenic effects) versus placebo, taken twice daily in 26 men with mild to moderate androgenetic alopecia over 25 weeks 72). The primary endpoints of hair loss arrest and qualitative hair improvement were assessed objectively by researchers and subjectively by study participants via a standardized 7-point scale questionnaire. Saw palmetto demonstrated 60% “improvement” in hair loss arrest and overall quality versus 11% among placebo. The active tablet also showed greater conservation of hair density and quality over time, as subjectively assessed by the study participants 73).
The largest randomized controlled trial to date compared oral 320-mg Saw palmetto-containing tablets versus 1-mg finasteride daily in 100 men with androgenetic alopecia over 2 years 74). Measurement of hair density was assessed by standardized global photography; the effectiveness of the treatment was evaluated with a 7-point clinical score scale as determined by 3 expert dermatologists experienced in the field of alopecia 75). Notably, 68% of patients treated with finasteride had higher hair density scores from baseline as compared to 38% of the Saw palmetto group (p < 0.05), indicating that Saw palmetto is inferior to finasteride. Although neither treatment was reported to be clinically effective in 10% of patients, Saw palmetto had stabilized progression of androgenetic alopecia in 52% of cases 76).
A 24-week, prospective cohort tested the efficacy of a topical Saw palmetto-containing lotion applied to the entire scalp daily for the treatment of androgenetic alopecia in 50 men 77). Study participants also applied a concentrated Saw palmetto-containing serum dedicated to thinning areas of the scalp for the first 4 weeks 78). Increased hair count was assessed via macrophotographic techniques using the Canfield photography system; hair restoration (defined by average hair size and terminal hair count) along with change in androgenetic alopecia staging was assessed via the Norwood-Hamilton grading system of pictures. Investigator satisfaction and patient satisfaction were measured via photographic and self-perceived assessment questionnaires, respectively, using a 7-point scale. Total hair count increased at 12 and 24 weeks compared to baseline by 3.4 and 4.9%, respectively, while terminal hair count increased by 21.4 and 74.1%, respectively. Medium-sized and vellus hair counts decreased at 24 weeks compared to baseline by −10.3 and −25%, respectively. Median androgenetic alopecia stage changed from 4 at baseline to 3 at 24 weeks, with a slight increase of hair over the anterior and vertex scalp, as well as higher patient satisfaction scores noted at study completion 79).
The most recent randomized controlled trial tested the efficacy of a 100-mg Saw palmetto-containing food supplement (Lambdapil®, ISDIN, Barcelona, Spain) on 35 men with androgenetic alopecia, for 6 months 80). Outcomes were measured via phototrichogram, where digital images evaluating hair volume and appearance were assessed by dermatologists through a 7-point clinical score scale. Further outcomes were also subjectively evaluated by study participants via completion of self-assessment surveys regarding perceived treatment efficacy. There was a 23.4% increase from the baseline anagen/telogen ratio. An additional 3.7% increase in total anagen hair percentage (vs. 0.8% decrease), and a 3.7% decrease in total telogen hair percentage (vs. 0.8% increase), was noted among the active Saw palmetto cohort as compared to placebo at 6 months. Patients reported increased hair volume, improved quality of life (QOL), and enhanced self-perceived efficacy using the Saw palmetto-containing tablet 81).
A prospective, noncomparative cohort tested the efficacy of a nutritional compound containing 300-mg Saw palmetto taken twice daily for 6 months in 15 males with androgenetic alopecia and 15 females with either female-pattern hair loss, severe telogen effluvium, or stress and food-deficiency induced hair loss 82). Evaluation of hair loss and hair health parameters was performed via trichoscopy. Global photographs assessing hair density were evaluated by experts on a 7-point scale, and subjective participant efficacy was measured via standardized questionnaires. An increase in hair density at 6 months was noted among 83.3% of study participants, with “greatly increased” density described by 26.7% of men and 33.3% of women. 93.3% of the subjects reported “general reduction” in hair loss, with 79.0% defining it as “significantly high,” 83.3% reported thicker and bulkier hair, 90.0% felt their hair was stronger with a better combing effect, and 88.5% reported reduced greasiness. At the end of the study, 93.0% of patients were “satisfied” with the results. The supplement was well tolerated 83).
A case series described 3 women with various hair loss patterns and 1 man with early onset androgenetic alopecia, who were successfully treated with Nutrafol® oral supplements (Nutraceutical Wellness Inc., New York, NY, USA) which include an undisclosed amount of Saw palmetto extract 84). Subjective outcomes included enhanced hair growth, improvement in temple area coverage, decreased shedding, and self-reported satisfaction with treatment outcomes, as noted amongst all study participants 85).
Saw Palmetto dosage
The dose of the standardized liposterolic Saw palmetto extract (85 – 95% fatty acids and sterols) used in the majority of clinical studies on BPH is 160 mg twice (320 mg) per day. Clinical results may be seen in six to eight weeks, although a six-month trial is the minimum to assess clinical efficacy.
Saw Palmetto side effects
Saw palmetto is well tolerated by most users. Saw palmetto may cause mild side effects, including digestive symptoms such as nausea, constipation, and diarrhea 86) and headache. Saw palmetto does not appear to affect readings of prostate-specific antigen (PSA) levels, even when taken in higher-than-usual amounts. PSA is a protein produced by the prostate gland. PSA levels have been used to screen for prostate cancer and are also used to monitor patients who have been diagnosed with prostate cancer. Additionally, likely associated with its hormonal effects, Saw palmetto has been reported to cause vasomotor symptoms in premenopausal females and was suspected as a cause of early menarche in young girls 87), 88). A report by Miroddi et al. 89) described hot flashes in an 11-year-old girl that appeared after 2 months of treating telogen effluvium with a food supplement containing Saw palmetto. The hot flashes ceased when the product was discontinued; however, 45 days after cessation the girl experienced menarche. Another report by Morabito et al. 90) also described similar vasomotor symptoms in a 10-year-old girl after 3 months of treating hirsutism with a food supplement containing 320 mg of Saw palmetto extract. As in the prior report, here too the symptoms ceased upon discontinuation of the supplement and the girl experienced menarche shortly thereafter. Topical agents containing Saw palmetto extract have also been associated with minor side effects including cold sensation, mild burning, unpleasant smell, itchy scalp, acne on the forehead, and allergic contact dermatitis 91), 92).
Saw palmetto has not been shown to interact with medications. Saw palmetto has been shown in multiple human trials to have no inhibitory or inductive effect on CYP1A2, CYP2D6, CYP2E1, or CYP3A4 93). Therefore, saw palmetto should not have adverse effects on medications that are metabolized by these enzymes.
Information on the safety of Saw palmetto comes primarily from studies in men. Little is known about the safety or side effects of Saw palmetto in women or children. Saw palmetto may be unsafe for use during pregnancy or while breastfeeding. There is a concern that Saw palmetto’s antiandrogenic properties pose a risk to males in utero because of the potential for deleterious effects on male genitalia 94). It is well understood that testosterone, an androgen, or male sex hormone, is required for developing and maintaining masculine sexual characteristics. Testosterone is converted to the most active androgen DHT by 5-alpha-reductase enzyme, which then exerts the androgen action via androgen receptors. In vitro data consistently demonstrate that saw palmetto extracts inhibit the testosterone conversion to DHT, including by inhibiting the 5-α-reductase enzyme. They also inhibit binding of DHT to androgenic receptors. Both of these actions would inhibit the androgen pathway if they occurred in vivo. Inhibitors of 5-alpha-reductase are known to cause adverse effects and are thus contraindicated in women who may become pregnant. They are classified as pregnancy category X, the category indicating the greatest concern for pregnant women. The pregnancy category X of these drugs results from teratogenicity studies in animals. These studies have shown that male offspring of animals (including monkeys) that consumed 5-α-reductase inhibitors exhibit abnormal male genitalia development. At the present time, the weight of scientific evidence suggests that consumption of Saw palmetto poses a risk to unborn male fetuses.
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