2. molecular targets 2.1. Stress hormone receptors Oleic acid and lauric acid obtained from Palmetto reference

2. molecular targets

2.1. Stress hormone receptors

Oleic acid and lauric acid obtained from Palmetto reference standards of these two fatty acids, appears to reduce the prazosin binding to α1-adrenergic receptors. [8] IC50 to prevent prazosin binding 41.8-46.3μg / ml and 84 -92.1μg / ml of oleic acid and lauric acid, respectively. [8] I have found a subsequent study that saw palmetto oils (Genesis unspecified) prevents the law from both prazosin and tamsulosin for α1-adrenergic receptors. [11]

It is believed that this reduction in ligand binding to occur and not through a competitive mechanism as saw palmetto appeared to reduce the total number of binding sites in the α1-adrenergic receptors and (when tested in isolation) points by the receiver. [11]

In vitro studies have shown that saw palmetto components adversely affect the ability of bonds to Rbt- α1 stress hormone receptors, and inhibition of downstream signals.
Was found on the oral ingestion of saw palmetto extract supercritical CO2 6-60mg / kg in mice within four weeks to increase Bmax (binding overall capacity) of prazosin receptor stress hormone α1 expressed in prostate [12] indicating a chronic adjustment in exchange acute effects.


2.2. Cholinergic receptors

Oleic acid and lauric acid derived from Palmetto and reference standards of these two fatty acids, it seems that the convergence of muscarinic receptors with the values ​​IC50 (to reduce the binding of the N-methylscopolamine (NMS) in brain tissue) from 70.6 to 91.3 micrograms / ml and 157. 163μg / ml, respectively. [8]

It was found chronic ingestion of 0.6-60mg / kg of supercritical CO2 extract of saw palmetto to reduce the Bmax (total binding affinity) of the NMS in the bladder at all doses tested. [12]


2.3. Ion channels

After they have been observed both oleic acid and lauric acid to reduce the binding of the drug Alasradepen 1,4-DHP (dihydropyridine) receptors, [8], which is a calcium-channel receivers. [13] The IC50 of oleic acid in the prevention of drug binding Alasradepen 33.3 -50.6μg / ml while the IC50 of lauric acid was 65.7-79.5μg / ml. [8]


2.4. 5α reductase

Extract of CO2 supercritical used in the tests (Sabalselect [14]) has been tested for its actions 5α reductase in mice, it was found that two of the components, oleic acid and lauric acid, fatty acids inhibit the activity of this enzyme IC50 values ​​of 54.3-54.5μg / ml and 66.2-67.6 μg / ml, respectively. [8] The inhibitory action along the lines of fatty acids that have been obtained from other sources, compared with those obtained through the saw palmetto. [8]

The study found a human attempt to assess the 5α reductase activity in response to 160 mg of extract of lipidosterolic that after one week of supplementation that both testosterone and DHT in serum were not affected compared to baseline. [15]



3. Pharmacy

3.1. Phase I metabolism

Saw palmetto to have an inhibitory effect on CYP2C8 activity, and an estimated value of IC50 of 15.4 +/- 1.7μg / ml, which in theory could be relevant physiologically has been shown. [16]



4. Cardiovascular Health

4.1. Heart tissue

A study conducted on mice that manage 60 mg / kg of supercritical extraction CO2 by mouth for four weeks increased prazosin binding to receptors α1 adrenergic in cardiac tissue by 30.5%, the effect is not noticeable for 6 mg / kg or less; no dose in 0.6 -60mg Group / kg affected muscarinic receptors Bmax (maximum binding capacity Legend). [12]



5. Inflammation and Immunology

5.1. Mechanisms

In keratinocytes trreated factor of stress inflammatory factors (LPS), a mixture of Palmetto with L- Carnitine and acid alpha-lipoic -0.1% medium (ratios unspecified) was the actions of anti-inflammatory and according to assess the changes in some vital signs (CCL17, CXCL6, and Allikotren B4). [17] Due to the effects of saw palmetto in isolation were not studied in this particular study, but it is not clear what the individual component (s) of this mixture in charge of the anti-inflammatory activity.

Observed anti-inflammatory effect with Permixon® extract hexane lipidosterolic saw palmetto, in human prostate cells (BPH-1, WPMY-1, and PC3) concentrations 10-56μg / ml by reducing the expression and the content of chemokine (MCP-1 / CCL2) and factors adhesion (VCAM-1). Been replicated [18] This effect in another study using the cell line BPH, where many downregulated genes involved in inflammation leads to inflammatory effect of a small number of cytokines (IL-6, IL-15 and IL 17) being suppressed. [19]



6. interact with hormones

6.1. Androgens

A supercritical CO2 extract used in the tests (Sabalselect® [14]) has been tested for its actions 5α reductase in mice, it was found that two of the components, oleic acid and lauric acid, fatty acids inhibit the activity of this enzyme with IC50 values ​​of 54.3-54.5 μg / ml and 66.2-67.6 μg / ml respectively [8] (lauric acid has been observed to peak efficiency in 200μM [7]). This was similar to the effect of an inhibitor of fatty acids that have been obtained from other sources, compared with those obtained through the saw palmetto. [8] in other places after the fatty acids tested at higher concentrations (2 mm) and found effective Myristic acid [7] which is known to the present also in Palmetto. [8]

Other studies have found that the assessment of saw palmetto extract from the hexane extract of saw palmetto (Permixon®) in insect cells to express the type of DNA 5α reductase I 5α reductase inhibitied isomer with IC50 of 4μg / ml while also preventing type II 7μg isomer / ml; [20] It has been assumed this power, but not confirmed, that this is due to the aliphatic fatty acids are known to interact with this enzyme [21] have found other studies using this effectively extract at a concentration of 10 micrograms / ml (plasma concentration is calculated therapeutic dose oral ) [22] [10] even 72-76% inhibition of both Aesfurmes. This efficiency is similar to finasteride (83%) in the therapeutic concentration of 5 nm. [10]

It was found that this effect damper to reduce the synthesis of DHT from testosterone in the prostate epithelial cells, where the local synthesis of DHT's happening more, and prostate fibroblasts. Permixon® was extracted and IC50 less than 10 micrograms / ml in fibroblasts and 70 μg / ml in the epithelial cells. [23]

Specifically the hexane extract, saw palmetto seems to prevent the two isomers of 5α reductase enzyme concentrations that approximate plasma concentrations reached via oral ingestion of the supplement. It has been proven that these inhibitory effects to reduce the formation of DHT in the laboratory, and although it is less powerful than it appears to be comparable to the effectiveness of finasteride. Not sure what molecule (s) mediate this purpose, as we have seen in extracts much larger than in the diet of fatty acids power saw palmetto.
It has been observed in prostate cancer cells (LNCaP) that while finasteride suppresses the activity of the type II isomer 5α reductase with other effects (suppress the secretion of PSA and down regulate the androgen receptor prostate), and saw palmetto can not downregulate the androgen receptor or the effect of secretion rates PSA. [10]

This is an excerpt from Palmetto also failed to influence the binding to the androgen receptor promoter in LNCaP cells. [10] In another study using human foreskin fibroblasts observed inhibitory effects on DHT bind to each of the cytosolic and nuclear receptors (the latter believed that androgen) receptors. [24]

There is mixed evidence on the effects of saw palmetto in androgen receptors.
Study the use of the saw palmetto combined with Haematococcus pluvialis astaxanthin source 800-1,200mg one day (doses of specific constituents and the type of extracting non-specific) found an increase in testosterone in a range of 1200 mg 3804% compared to placebo when used in the context of 14 days we did not reach statistical significance. DHT is specified low volume seems to reach significance. [2] Other evaluation studies on saw palmetto testosterone confused Similarly with other nutrients [25] [26] [27] [28] with the study using saw palmetto (extract lipidosterolic) in the isolation of 160 mg more than a week not to influence testosterone or serum DHT concentrations relative to baseline (as finasteride was effective in reducing DHT). [15]

Evaluation studies of saw palmetto testosterone currently very confused with other nutrients or have a potential conflict of interest. A single study, which lasts only one week using saw palmetto in isolation failed to find any effect on testosterone or DHT.


7. Peripheral Systems

7.1. Urinary Tract

I saw palmetto mechanisms that are thought to be related to be placed in the lower urinary tract include deleted α1- adrenergic signals, and 1,4-dihydropyridine muscarinic receptors. [14] [12]

It has been observed in mice using the extract of saw palmetto (CO2 supercritical) to 0.6 mg / kg 0.6 mg / kg or 60 mg / kg daily for four weeks to increase values ​​Bmax (maximum number of binding) of prazosin in the prostate in two locations higher doses of 23.6 to 36.7%, while the highest dose affected the spleen (26.1%), heart (30.5%) only. [12] It has been observed the opposite effect where Bmax muscarinic receptors in the bladder fell highest two doses (31.8 to 41.2%) with a decrease in the gland under the jaw 60 mg / kg (17.9%) and a slight increase at 0.6 mg / kg (13.8% ). [12]


7.2. Prostate

6-60mg / kg of supercritical extraction CO2 from Palmetto, when administered orally to rats for four weeks prazosin increase Bmax in the prostate by 23.6% up to 36.7. 0.6 mg / kg was ineffective. [12]

A retrospective of 320 mg Peroxim study in men with benign prostatic hyperplasia with PSA less than 10 ng / ml found that circulating PSA levels appeared to decrease from 5.39ng / ml 4.38 ng / ml for (19%) during the study for six months. [29]



8. interact with the metabolism of cancer

8.1. Glioma

/ Found ml study in tumor cells (U87 and U251) using Saw Palmetto from 1 g to the nursery was able to reduce the protein content of PI3K (involved in the path known signals to play a role in promoting the invasion of the cell [30] lines [31 ]) and prosurvival My C-XL protein in both cell lines, while p53 protein showed differential effects depending on the cell line. [32]


8.2. Prostate

LNCaP cancer cells PC3 deal with the extract of saw palmetto lipido (44 or 88μg / ml) was found concentrations of whether they are able to reduce the number of cells tested three points of time (24.48, and 72 hours) [33] While it seems CD45 - / CK5-CK8 + removed from patients with prostate adenocarcinoma cells also have a reduction of 44μg / ml of this excerpt, which pushes cells and intervened in the growth NF- KB. [33]

One trial (open without supervision) using formulaton saw palmetto with seven other herbs (out of known as PC-SPES commercial structure [34]) found an improvement in PSA levels in 10 threads registered with hormone refractory prostate cancer after 24 weeks of treatment. [35] remove weeds that PSA levels return to baseline. [35]



9. aesthetic reactions

9.1. Hair

Male pattern baldness, also known as androgenetic alopecia, hair loss is androgen dependent largely dependent disorder of dihydrotestosterone (DHT) produced by 5α reductase enzyme that. [36] There are isomers of this enzyme with 5α type shorthand II more strongly involved in hair loss that leads to the selective type inhibitor 5α reductase II, finasteride, which achieves success in preventing baldness is associated with androgen (regardless of biological sex [37] [38] ). Despite the abundance of type II Aesfurmes in the hair follicles, inhibiting both type I and type II may be more effective in preventing hair loss as dutasteride (an inhibitor of both) of finasteride. [39] have been studied [40] saw palmetto in male pattern baldness because of the presence of inhibitory action against both Aesfurmes of the enzyme. [8]

Liposterolic saw palmetto extract (200 mg of 85-95% of the content liposterolic) combined with 50mg β- sitosterol and some vitamins B (100 micrograms of biotin, niacin 15 mg) in 10 healthy men with androgenetic alopecia 24.7 18. During the weeks and found that 60% of Patients have improved hair (investigator assessment of blind) compared with placebo in the subject, even though the objective is not to take action. [1] Subsequent study of the use of evaluation of 320 mg of saw palmetto in two years, in healthy men with male pattern baldness pointed out that 38% of patients treated with saw palmetto reported an increase in hair that performs less effective than finasteride 1 mg growth (66%); it seemed Saw palmetto is mainly to work in the crown of the head while finasteride was effective in the crown area and the front. [41]

It is known Dihydrotestoterone (DHT), produced by the two isotopes of 5α reductase enzymes to play a role in male pattern baldness. Since saw palmetto both similarities prevents the enzyme, has been studied in humans, and it seems to be effective to some extent on the basis of limited evidence, but not as effective as finasteride.


10. interaction with medical conditions

10.1. Benign prostatic hyperplasia (BPH)

Saw palmetto can affect benign prostatic hyperplasia (BPH) prevents 5α reductase [8] and connects to α1 stress hormone receptors, [8] and both molecular targets for BPH (assuming α1- adrenergic receptor inhibition). [42]

With regard to prostate-specific antigen (PSA), a biomarker for prostate cancer, and treatment of the cells that contain a mixture saw Permixon® has been observed Palmetto to inhibit the enzyme 5α reductase in 10 micrograms / ml (up to 72-76% with similar strength among Aesfurmes) without affecting the the secretion of PSA [22] [10], even when the culture is stimulated with testosterone or DHT. [22] [10] and this effect varies from finasteride, in therapeutic concentrations, and the suppression of the increases caused by DHT from PSA. It is believed [10] this contradiction to be due to how to organize the PSA before androgen [43] as saw palmetto does not interfere with androgen, referring to the prostate cell. [10]

Saw palmetto prevents 5α reduction in prostate cancer cells in the laboratory, but does not affect the levels of PSA. This may be because he saw palmetto does not interfere with androgen, referring to the prostate cells, and PSA is regulated by androgens.
Saw palmetto has been the subject of many studies and descriptive analyzes for BPH, with mixed results.

Early trial found that saw palmetto increases the flow of urine and reduces frequent urination during the night in patients with benign prostatic hyperplasia. [44]

I found, another study in early double-blind placebo-controlled than 320 mg per day Permixon® significant improvement in many of the symptoms of BPH on placebo. [45] After a retrospective study in men who suffer from urinary symptoms caused by benign prostatic hyperplasia (without prostate cancer and PSA less than 10 ng / ml) 320 mg given saw palmetto (Permixon®) for six months confirmed this. Have been found [29] improvement in urinary symptoms in Palmetto is used alone, and when used in conjunction with alpha inhibitors, while saw palmetto only showed better responses amidst size vanity and intermittent flow of urine, while the combination therapy faster than the peak flow improvement. [29]

Another study using the saw palmetto with tamsulosin (α1-adrenergic receptor antagonist) during 6-12 months in men with combination therapy BPH found more effective than tamsulosin alone [46], while the combination therapy with selenium (50 micrograms) and lycopene (5 mg) by supercritical extract of the saw palmetto (320 mg) appeared to perform equally to 400 micrograms tamsulosin after year to improve urinary symptoms and erectile dysfunction. [3] tamsulosin add this combination therapy increased more benefits [3].

In spite of these positive individual results, the Cochrane review later concluded that saw palmetto better than placebo for many aspects of BPH is. [47] This is in contrast to the conclusion of the previous Cochrane review that saw palmetto to be effective. [48] ​​The reason given for the opposite end due to the fact that most previous studies in the review were short and lack of energy are called, and validated also used measures of results. And it included a review of the later experiments [49] [50], which uses international verification of good health as a result of prostate symptoms. The first showed a slight improvement, barely large in this regard, and not the second. By taking these studies into account, along with other recent studies, authors of the review concluded that there was no significant benefit on placebo, but I will say that the evidence is mixed to some extent. [47] review of the recent Cochrane group, which included two new studies found a statistically significant for the night and the symptoms reported by patients, but it is not statistically significant for Score the American Society of Urological effects, urine peak flow, rating the doctor improved symptoms, or the size of the prostate in studies compared with placebo. [51]

Evidence to show the effects of saw palmetto for BPH to be mixed. Several small studies some benefits have been found, but the largest, well-conducted studies tend to find any benefits or weak, with search recent systematic review of some great benefits to placebo.


11. Safety and Toxicology

11.1. Public

Saw palmetto contains tannic acid, which bind and reduce iron bioavailability. Have also been reported [52] sexual weakness simple, perhaps through pro-estrogenic effects. Beyond that, side effects are not distinguished from placebo. [53]


11.2. Case studies

I saw two reports the case of inflammation of the pancreas may repoted Palmetto. [54] [55] and in one case was reported liver damage. [56]

A case study of a young (11 years) because of saw palmetto to treat hair loss loss (a type of hair loss) who suffered from hot flashes that are no longer Annex when he was no longer taken. It was seen as likely that these side effects were due to be completed use. [57] The second case on the 10-year-old described the study as hot flashes when taking supplements containing saw palmetto for hirsutism. [58] appearing hot flashes after a new challenge, and began menstrual four months after taking the supplement. [58]