Having been shown effective as an herbal medicine for testicular conditions, prostate irritation and urination frequency problems for centuries in traditional medicine, numerous studies on Saw palmetto (Serenoa repens or Serenoa serrulata) for prostate conditions illustrated its effectiveness.
But two recent reviews have seemingly stolen away Saw palmetto's shine. This has forced us to ask: Are the reviews credible? And more importantly, is Saw palmetto useful for prostate conditions or not?
In other words, was Saw palmetto's long-lived reputation for easing urinary difficulties and prostate enlargement and its subsequent inclusion into the US Pharmacopoeia and National Formulary in the early 1900s all a big hoax?
The condition on center stage is benign prostatic hyperplasia (BPH). This is a condition whereby the prostate's epithelial cells and stromal cells are significantly increased in men. As their numbers and density increases, the prostate enlarges and puts pressure on the urethra – the canal through which urine flows. This pressure causes urination problems – including greater frequency and a lower flow rate. Pain can also result. Up to three-quarters of men over 75 will have BPH, with most cases starting between the ages of 45 and 50 years old.
Just what is hyperplasia? It is an expansion of cells and tissue typical of inflammatory conditions.
The seemingly game-changing Saw palmetto/BPH review came from the University of Minnesota Medical School and the U.S. Department of Veterans Affairs (Macdonald et al. 2012). The researchers – led by Timothy J. Wilt, MD, a long-time researcher from Veterans Affairs and a professor of medicine at the University of Minnesota Medical School – concluded that Saw palmetto's effects on prostate enlargement were no better than placebo.
Surprisingly, the review only covered three studies. While their initial analysis looked at 17 studies including 2,008 patients, and a previous study by some of the same researchers (including Dr. Wilt) examined 21 studies with 3,139 patients, the researchers eliminated all but three studies, which covered only 661 patients.
The researchers basically eliminated any study that did not use the American Urological Association's Symptom Index or the International Prostate Symptom Scores method to evaluate prostate improvement.
These three studies concluded that Saw palmetto (Serenoa repens) supplements – even when (in one study) doses were increased by two and then three times – were no better than placebo in reducing prostate symptoms.
This negative review is bolstered by another larger Cochrane review led by Dr. Wilt in 2009. This review narrowed 30 studies of 5,222 men down to 18 double-blinded and randomized trials. This review also found that Saw palmetto extracts were no more effective than placebo for improving urinary symptoms, increasing peak urine flow or decreasing prostate size. While Saw palmetto appeared to significantly reduce nighttime urination frequency (nocturia), a "sensitivity analysis" on those results concluded no significant improvements with Saw palmetto treatments.
Yet this finding conflicts with numerous randomized, double-blind studies and previous reviews that have found Saw palmetto reduces prostate symptoms.
For example, a previous Cochrane review, this one also from the most of the same researchers (Wilt et al. 2000), after reviewed 44 studies between 1966 and 1997, selecting 18 double-blinded studies. An analysis of these studies showed that Saw palmetto decreased nocturia by an average of .76 times per night per person (nearly one less urination per night). They also found that men taking Saw palmetto experienced a 72% average improvement of BPH symptoms.
Furthermore, among four studies that compared Saw palmetto with the pharmaceutical Finasteride, Saw palmetto resulted in BPH symptom improvement "comparable to men receiving the finasteride" according to the researchers.
The researchers concluded: "Serenoa repens appears to be a useful option for improving lower urinary tract symptoms and flow measures."
Another study review, again by some of the same researchers (Wilt et al. 2002), reviewed 21 studies involving 3,139 men. Of these, 18 were found to be double-blinded, and of those, seven were eliminated to leave 11 studies with high quality controls and full randomization under Cochrane review criteria.
This review found that Saw palmetto improved urinary symptom scores by about 7.5% over placebo, while reducing nocturia by 24%. Self-reported improvement of symptoms among the Saw palmetto groups averaged 76% higher than placebo groups in these studies.
In two of those studies, Saw palmetto supplementation showed similar improvement in symptom scores as the pharmaceutical Finasteride, but with fewer side effects and 18% fewer people withdrawing from the studies.
The researchers concluded: "The evidence suggests that Serenoa repens provides mild to moderate improvement in urinary symptoms and flow measures. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events."
Note that these two large reviews eliminated many good quality studies that also showed Saw palmetto's effectiveness. Even after their removal there were still plenty of high quality studies that were double-blinded, placebo-controlled and randomized showing Saw palmetto's effectiveness.
For example, researchers from UCLA headed by Dr. Jianyu Rao (2008), randomly assigned 92 men to either receive two capsules of a Saw palmetto extract or a placebo each day for three months. After the treatment period, the researchers found that maximum urinary flow rate increased significantly among those taking the Saw palmetto extract (14 milliliters per second vs. 12). The "relative urinary resistance" was also 20% lower in the Saw palmetto extract group (2.4 compared to 3.0).
The Holes in Pharmaceutical Oriented Research
As we look at the later reviews, we find an increasing number of studies are being eliminated, not because they were not valid studies, or perfectly acceptable to most scientists, but because they did not match the increasingly tighter protocols being applied to pharmaceutical research.
Notably in the case of Saw palmetto, the ability of researchers to utilize subjective feedback from study subjects.
In other words, the full range of individual experiences, which may be slightly different for each person depending upon their health status and lifestyle, is virtually being eliminated by pharmaceutical-oriented research.
This has been proven to be extremely helpful for pharmaceutical researchers, because it enables many individual responses such as "I felt doped up" or "I felt groggy" after taking the pharmaceutical to be virtually eliminated from pharmaceutical research conclusions. These subjective responses are replaced by often uncategorized responses, or those that can be spread out into seemingly unimportant and low-percentile quantifications of negative reactions.
The use of traditional herbs typically comes with just the opposite. People who take traditional herbs can have varying degrees of success with their condition, at the same time experiencing other positive effects such as better sleep, clearer thinking and more energy. These kind of subjective responses, once utilized as a sub-component of herbal research in the past, has become virtually eliminated or constricted down to a statement such as "most patients tolerated the supplement well."
Without some room for subjective responses or some variance in methodology, seemingly positive effects from an herbal supplement can be hammered down to "insignificant" or "no better than placebo" by simply applying strict requirements on what qualifies as improved symptoms. This is how the 2009 Saw palmetto study was able to whittle "significantly improved nocturia" results down to "insignificant" through "sensitivity analysis."
In addition, herbal medicine trials have often come from non-traditional research centers where pharmaceutical-oriented research may not have been the foremost element of focus. A non-traditional research center may apply a different type of symptom index or a more subjective effectiveness score, for example. These studies, despite their being controlled in multiple respects, are often eliminated and labeled "low quality."
Some herbal medicine research has also utilized combination therapies to the single herb being tested. These are also typically eliminated from such reviews.
But there are other reasons we can point to with regard to applying pharmaceutical research constraints onto herbal medicine research, and in particular, the Saw palmetto research.
Herbal medicine therapy typically comes with several important differences from pharmaceutical therapy
- Herbal medicine typically comes with few if any adverse side effects;
- Herbal medicine typically requires longer treatment periods before their benefits take their full effects;
- Patients often respond uniquely to herbal medicine therapy, with varying positive healing effects;
- Herbs contain a variety of constituents and thus different extract forms can contain more or less of the synergy of bioactive substances;
- In most clinical settings, herbal medicine is typically given in combination with other herbal medicines and diet therapies.
The first point – that herbal medicines typically come with few if any negative side effects - has been well established among herbal research for several decades now. This has also been confirmed by comparing epidemiological data between pharmaceutical use and herbal supplement use. The number of illnesses and deaths from herbal supplements are typically in the single digits per year. The 2007 annual report of the American Association of Poison Control Centers reported a grand total of three (yes, 3) deaths from natural remedies during the year. This included herbs, homeopathy, essential oils, minerals, vitamins and other supplements.
In comparison, some studies have reported that over 100,000 Americans die each year from taking correctly prescribed pharmaceuticals. A 1998 report from the University of Toronto estimated that approximately 106,000 people die each year from taking pharmaceuticals (Lazarou et al. 1998). Added to this are deaths from illegal use and overdosing of pharmaceuticals.
This report also calculated that 2,300,000 people will report either ending up hospitalized, permanently disabled, or fatally injured per year as a result of pharmaceutical use in the United States.
A case in point is the pharmaceutical typically used for BPH, Finasteride. Recent research has revealed that Finasteride comes with some serious side effects, including sexual dysfunction, which can continue after treatment is discontinued. These include erectile dysfunction, ejaculation disorder, and impotence (as high as 18% in some research), abnormal ejaculation (as high as 7% in some research), and gynecomastia (large breasts in men) (as high as nearly 3%). Anxiety and depression have also been seen in Finasteride patients.
Yet we find in all the reviews mentioned above that Saw palmetto treatment comes with few if any adverse effects.
Saw palmetto, proven to lower 5α-reductase just as Finasteride does, comes not only with no known adverse side effects: Saw palmetto also produces numerous positive side effects, known clinically among herbalist doctors. These include, believe it or not: increased libido and increased sexual potency.
Wait a second. While Finasteride has been shown in numerous studies to cause sexual impotency while inhibiting 5α-reductase, Saw palmetto also inhibits 5α-reductase while apparently increasing sexual potency? Clinical research has not confirmed its aphrodisiac effects, but traditional use indicates that at least Saw palmetto does not come with the sexual dysfunction side effects of Finasteride.
Let's talk a bit more about 5alpha-reductase, DHT, prostate and Saw palmetto.
DHT and 5alpha-reductase
The link between 5alpha-dihydrotestosterone (DHT), 5alpha-reductase and prostate enlargement is well documented. It is also the basis for the pharmaceutical drug Finasteride. Like Saw palmetto, Finasteride is considered a 5alpha-reductase inhibitor. The two best known drugs containing Finasterid are Propecia – used for baldness – and Proscar – used for prostate hyperplasia. Propecia contains 1 milligram of Finasteride while Proscar contains 5 milligrams.
Herbs such as Saw palmetto have also been shown to naturally lower DHT levels. Saw palmetto inhibits 5α-reductase but it also blocks DHT receptors on cell membranes. A 2002 alopecia study (Prager et al. 2002) of ten balding males found that a combination of Saw palmetto and beta-sitosterol resulted in 60% of the men showing significant hair regrowth.
Researchers from Stockholm, Sweden (Iglesias-Gato et al. 2012) found that Saw palmetto extract inhibited two critical mechanisms involved in prostate cell proliferation: Epidermal growth factor and lipopolysaccharide inducement. Their tests on human androgen-independent epithelial prostate cell lines – shown to proliferate in prostate hyperplasia – illustrated that Saw palmetto extract was productive for inhibiting prostate enlargement on a cellular basis.
The researchers also found that Saw palmetto inhibited monocyte chemotactic protein-1 (MCP-1) secretion related to inflammatory factor IL-12. It also reduced granulocyte-macrophage colony-stimulating factor (GM-CSF). These results showed that Saw palmetto also reduces inflammatory factors related to hyperplasia.
Another laboratory study – this from Barcelona (Pias 2010) – found that Saw palmetto extract significantly reduced 5alpha-dihydrotestosterone (DHT) levels by reducing the enzyme associated with prostate hyperplasia, 5alpha-reductase.
Reducing DHT levels by inhibiting 5alpha-reductase has been the promised silver bullet for reducing prostate hyperplasia. However, it is a bit more complicated that this.
Later in life, as a man's testosterone levels drop, DHT levels will often increase by virtue of more oxidative stress, less exercise and poor dietary choices. Thus, oxidative stress has often been associated with high DHT levels. Not surprisingly, many researchers now accept that DHT is a marker for ongoing oxidative stress.
Researchers from the University of Connecticut School of Medicine studied 1,083 Caucasian men. Of the study group, 531 of the men were diagnosed with alcohol dependence. The researchers discovered that those in the alcohol-dependent group tended to have higher DHT levels and lower testosterone levels. Because alcohol consumption is related to increased oxidative stress, the researchers were able to associate higher DHT levels and lower testosterone with increased alcohol consumption.
This provides the link to 5alpha-reductase. While 5alpha-reductase escorts the conversion of testosterone to 5alpha-dihydrotestosterone, other research has found oxidative stress linked to an increase in 5alpha-reductase. And there are in fact two 5alpha-reductase enyzmes – type I and type II.
Illustrating the complexity of 5alpha-reductase, earlier this year a study on periodontal disease found that heightened lipopolysaccharide levels, a byproduct of bacteria – in this case periodontal disease bacteria - was associated with higher levels of both DHT and oxidative stress (Tilakaratne and Soory 2012).
A Multitude of Constituents
The grand question becomes, why does the 5alpha-reductase inhibiting Saw palmetto not come with the same side effects as the 5alpha-reductase inhibitor Finasteride?
As opposed to the single-chemical Finasteride, Saw palmetto contains a multitude of constituents. These include beta-sitosterol and its related glucoside; various tannins; alkaloids; a number of resins; capric, palmitic, lauric, oleic and caprylic acids, carotenoids; lipase and others.
This goes to the heart of the difference between herbal pharmacology and the single-constituent pharmaceutical strategy. While synthetically inhibiting 5α-reductase helps reduce hyperplasia by lowering the conversion of testosterone to 5α-dihydrotestosterone (DHT), it also deprives the body of its natural androgen balance: Required to maintain a man's natural sexual function, mood and energy levels.
Because Saw palmetto contains a variety of naturally present phyto-compounds, it inhibits 5α-reductase without producing hormonal imbalances. This is confirmed by the fact that Saw palmetto is also used by traditional herbalists as an aphrodisiac. Saw palmetto also contains phytonutrients that help neutralize oxidation, thereby reducing oxidative stress. As illustrated in the research mentioned, by reducing oxidative stress, inflammation is decreased, and as inflammation is decreased, hyperplasia is decreased.
Whole Herbs versus Supercritical Extracts
Furthermore, most Saw palmetto supplements are standardized extracts of varying quality and method. Most are standardized to the fatty acids within the fruit. The modern extract method now typically used for Saw palmetto extracts is supercritical CO2 extraction with ethanol.
The assumption of supercritical CO2/ethanol extraction methodology is that this creates a more reliable standardization. But how does this affect the myriad of other natural constituents in the herb – which produce its synergistic effects?
Many of the herb's natural range of constituents and heat/light-sensitive nutrients are in fact, lost during the process of extraction.
For example, one study (Cathpole et al. 2002) of this CO2 ethanol extraction method processed raw Saw palmetto, St. John's Wort, Kava and Echinacea into standardized extracts. The standardized ingredients (such as kavalactones from Kava) yielded from 2% to 12% by mass as expected. However, this came at the price of losing other constituents. The researchers concluded that: "Other desirable actives, such as chichoric acid and associated polyphenolic derivatives were not extracted."
Simply the fact that some Saw palmetto extracts are not as effective as others should raise concern about the quality of those products used in Saw palmetto studies. Isn't it interesting that later Saw palmetto research – using increasingly standardized extracts – also accompanied worse results?
Confirming this variable, Ray Sahelian, M.D. has stated in a discussion of Saw palmetto extract: "In order for a Saw palmetto product to be effective, it should either supply a daily dose of 320 mg of 85 to 95% fatty acids, or 640 mg of a 45% fatty acid extract. Some products that do not have these high potency fatty acid extracts may not be as effective."
Dr. Pilar Pais has agreed with this premise, stating in his 2010 study published in the Journal Advanced Therapy, "these inconsistent results [in Saw palmetto research] may be due, in part, to varying bioactivities of the Saw palmetto extract used in the studies."
Medicinal herbs have traditionally been supplied as raw dried roots, fruits or leaves. Extraction methods included cold or hot water infusion (e.g., tea). Alcohol extraction methods have also been used in some cases, but these were not expected to duplicate the effects of whole herbs. Along with this wisdom came an understanding that heat, light and mechanical breakdown can cause irreparable harm to the efficacy of these whole herbs by reducing their synergistic phytochemical content.
Thus we find that the very benefit derived from using herbal medicines – their range of phytochemicals and nutrients that work synergistically – is contradicted by some modern methods of extraction.
Because our Western pharmacology education and biochemical research focuses upon finding that single "active" phytochemical, we miss the very essence of why natural compounds have provided healing benefits for thousands of year to billions of people around the world: Their synergy of related phyto-compounds.
A traditionally trained herbalist will therefore typically recommend only whole herbs or whole herb extracts.
This of course flies in the face of the "active constituent" mentality of our modern technologies and pharmaceutical-oriented biochemistry institutions. Nature works differently. Nature works by using synergy and balance. Nature creates equilibrium rather than radical response.
Simply put, herbal medicines work differently than pharmaceuticals. Herbal medicines provide an array of nutrients and phytochemicals that work in a synergistic manner. Many work partly by stimulating the body's own detoxification processes, which can effect people differently, depending upon their age, condition, diet and other factors.
We also find that a single herb or extract is rarely recommended for a particular condition by a traditionally trained herbalist. The traditional herbalist will typically prescribe a blend of whole herbs or whole herb extracts using a vast knowledge of herbal synergies. In fact, many of the most popular herbal combinations used among traditional medicines have been handed down over centuries and perfected through clinical application.
Confirming the efficacy of this approach, Dr. Wilt's 2000 review also found that Saw palmetto's effectiveness increased when used in combination with other herbs, including Hypoxis rooperi (Africa potato), Secale cereale (Rye) and Pygeum africanum (Pygeum or African prune).
Synergistic Cures for Synergistic Ailments
This synergy is mirrored by the variances among each condition. The condition of prostate enlargement relates not to a single cause, but largely to a combination of factors. Factors firmly associated with prostate enlargement include obesity, lower exercise levels and higher alcohol consumption (Parsons 2007). Factors suspected include diets high in saturated fats and fried foods, higher stress levels, and smoking. Diets that maintain a variety of whole food plant-based nutrients have been shown to decrease the risk of prostate enlargement (Setchell and Cassidy 1999).
Holistic practitioners often prescribe herbal combinations that might include Saw palmetto together with other herbs, as well as dietary and lifestyle recommendations. This approach may not be conducive to large-scale clinical ("single bullet") studies, but it has worked for billions of people over thousands of years.
This great tradition of herbal medicine is in fact being suffocated by modern medicine's "single bullet" approach to healing and research.
While standardized herbal formulations are used, traditional herbalists have typically provided prescriptive advice on a per-patient basis. The application of medicine as a one-drug-fits-all is a modern development in medicine. The traditional doctor prescribed herbal, diet and lifestyle remedies designed around the patient's history, environment and lifestyle.
Conspiracy or Mistaken Identity?
The reviews by Dr. Wilt and his various associates might seem to be iniquitous to some, as though there is a great conspiracy by the pharmaceutical industry and their minion medical schools to snuff out herbal medicines that pose a threat to pharmaceutical sales.
While this conspiracy theory has held attractive to some, and there have been fraudulent acts uncovered amongst a handful of pharmaceutical researchers, there is no need to go overboard. There are plenty of medical doctors, of which Dr. Wilt is probably one, who have a sincere desire to uncover the truth and help heal people. Many also see themselves as valiantly combating a handful of irresponsible herbal suppliers and quasi-herbal medicine proponents who make ridiculous claims about their herb-containing products.
The bottom line is that there are all kinds of people in the medical profession, and we cannot paint all pharmaceutical-oriented researchers as involved in a conspiracy just because a review doesn't confirm what we want it to confirm.
The fact is, herbal medicine is not applicable to pharmaceutical-oriented research. A whole herb's range of constituents, range of effects and combination therapies within which herbs have been used successfully over thousands of years simply cannot be fairly drag-raced against a single-bullet pharmaceutical.
They are two different species. And they come from two different worlds altogether.
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