Clinical Management Series: Natural Medicines Comprehensive Database

Natural Medicines in Clinical Management
of Benign Prostatic Hyperplasia

5-alpha Reductase Inhibitors | Antiproliferatives and Growth Inhibiting Supplements | Anti-inflammatory Supplements
Miscellaneous | The Bottom Line | References

Benign prostatic hyperplasia (BPH) is a very common problem in older men. Like gray hair, the chance of prostate problems increases dramatically with age. By age 60, over HALF of men have some prostate enlargement. By age 70, 90% have prostate enlargement. About a third of men over age 50 develop symptoms due to prostate enlargement.^{11215,11216,11217}

The prostate is normally a walnut-sized gland that produces seminal fluid. The prostate is affected by testosterone and estrogen. Both hormones contribute to increased levels of dihydrotestosterone (DHT). DHT increases prostatic cell proliferation and glandular size.

As men age, testosterone levels decrease and estrogen levels increase. Estrogen increases the number of DHT receptors in the prostate and also inhibits DHT metabolism.^{11215,11216,11288} These changes can lead to further enlargement of the prostate.

BPH involves hyperplasia (an increase in the number of cells) rather than hypertrophy (an increase in the size of cells). For practical purposes, the terms are interchangeable. BPH symptoms are caused by an increase in the number of cells in the prostatic epithelium and surrounding tissues. The enlarging prostate blocks the urethra, resulting in urinary symptoms. Interestingly, there’s no strong relationship between prostate size and severity of symptoms.

Men often wonder if BPH increases their risk for prostate cancer. It DOESN’T. BPH adversely affects the quality rather than the quantity of a man’s life.^11215,11218

But BPH symptoms can be very troubling for some men. Urinary incontinence can be socially debilitating. Nocturia can decrease sleep quality and affect daytime performance.¹¹²¹⁵

Symptoms of Benign Prostatic Hyperplasia^11215,11219
Voiding (Obstructive) Symptoms	Storage (Irritative) Symptoms
Hesitancy	Frequency
Intermittency (urinary stream stops and starts)	Nocturia
Decreased force of stream	Urgency
Abdominal straining	Urge incontinence
Incomplete emptying
Prolonged urination
Post-micturition dribbling

Treatment options for BPH consist of doing nothing, drug treatment with alpha₁-blockers and/or 5-alpha reductase inhibitors, or surgical treatment. Treatment decisions are based on the severity of symptoms and their effect on quality of life.¹¹²²¹

Many men turn to natural products to prevent or treat BPH, often in combination with conventional treatment.^11222,11123 Unlike natural products for many other health conditions, some products to treat BPH are good evidence-based alternatives to conventional drugs. Natural products for BPH work in several ways...anti-inflammatory effects, 5-alpha reductase inhibition, anti-proliferative effects, or a combination of these.

Commonly Used Conventional and Natural Medicines for Benign Prostatic Hyperplasia*

Alpha₁-Adrenergic Blockers
   Conventional Medicines
      Alfuzosin (Uroxatral)
      Doxazosin (Cardura)
      Prazosin (Minipress)
      Tamsulosin (Flomax)
      Terazosin (Hytrin)

5-Alpha Reductase Inhibitors
   Conventional Medicines
      Dutasteride (Avodart)
      Finasteride (Proscar)
   Natural Medicines
      Saw palmetto (Serenoa repens)^a

Antiproliferative
   Natural Medicines
      African wild potato (Hypoxis hemerocallidea)
      Beta-sitosterol
      Lycopene
      Pumpkin seed (Cucurbita pepo)
      Pygeum (Prunus africana)
      Red clover (Trifolium pratense)
      Soy (Glycine max)
      Stinging nettle root (Urtica dioica)

Anti-inflammatory
Natural Medicines
Rye grass pollen (Secale cereale)^b

Miscellaneous
   Natural Medicines
      Buchu (Agathosma betulina)
      Fireweed (Epilobium angustifoliumi)
      Flaxseed oil (Linum usitatissimum)
      Garlic (Allium sativum)
      Prickly pear cactus (Opuntia ficus-indica)
      Uva-ursi (Arctostaphylos uva-ursi)
   Nutrients
      Selenium
      Vitamin E^c
      Zinc

*Note: Many natural products are tried for BPH, but very few have reliable evidence that they work. Inclusion in this list does NOT imply that these products are effective for BPH.
^a May also have anti-inflammatory and antiproliferative
effects.
^b May also have alpha₁-blocking activity.
^c May also have antiproliferative effects.

5-alpha Reductase Inhibitors

Saw palmetto (Serenoa repens) is the best known and most widely used supplement for BPH. It has antiandrogenic, antiproliferative, and anti-inflammatory properties. Each of these might be responsible for its benefits in BPH patients. Saw palmetto seems to have some effects similar to finasteride (Proscar) and dutasteride (Avodart). They all inhibit 5-alpha reductase. Inhibiting 5-alpha reductase reduces prostate growth by preventing the conversion of testosterone to dihydrotestosterone (DHT).^{6765,6769,6770,6773} However, saw palmetto is less potent than finasteride and dutasteride.

Saw palmetto does not reduce prostate size like finasteride...but saw palmetto seems to shrink the inner prostatic epithelium.⁵⁰⁹³ Saw palmetto's activity appears to be prostate-specific. Saw palmetto might also slow prostate cell proliferation by inhibiting several growth factors and by stimulating the normal death of some prostate cells.^{6765,6769,6770}

Saw palmetto also seems to inhibit lipoxygenase and cyclooxygenase (COX) enzymes. These enzymes may be involved in prostate inflammation. A saw palmetto extract seems to lower markers of prostatic inflammation such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta.^{6769,6779,11224}

Most research suggests that saw palmetto provides mild to moderate improvement in many BPH symptoms...frequent urination, painful urination, hesitancy, urgency. Saw palmetto also decreases nocturia, improves peak and mean urine flow, and lowers residual urine volume in men with BPH.^{764,2732,6750,6751,6762,6764,6772,6773,6777,6778,
8330} Saw palmetto seems to be as effective as finasteride (Proscar), and saw palmetto might be better tolerated.⁶⁴²⁴ Saw palmetto doesn't seem to cause impotence as often as finasteride.^{764,6424,6762} Unlike finasteride, saw palmetto doesn't reduce prostate-specific antigen (PSA) levels. Finasteride can reduce PSA levels making prostate cancer monitoring more difficult.^2735,6771

Saw palmetto does not seem to be as effective as alpha₁-adrenergic blockers such as prazosin (Minipress) or selective alpha₁-blockers such as alfuzosin (Uroxatral) and tamsulosin (Flomax) for BPH symptom relief.^{6775,6776,8901} And saw palmetto doesn't work as quickly as alpha₁-blockers. Saw palmetto treatment for 1-2 months is usually necessary before men feel improvement.^{2732,6750,6778} But there's some research suggesting that saw palmetto might be as effective as tamsulosin for symptom relief after 12 months of treatment.¹¹²⁴³ Combining saw palmetto with an alpha₁-blocker such as tamsulosin doesn't seem to relieve symptoms any better than an alpha₁-blocker alone.^{6775,6776,8901}

Although most research is positive, not all research has shown a beneficial effect.^11314,14274 In a recent high quality study, saw palmetto was ineffective for reducing symptoms in men with moderate to severe symptoms of BPH after a year of treatment.¹⁴²⁷⁴ The reason for this inconsistent finding might be due to different outcome measures, product selection, or other factors.

For an analysis of the new study, click here to read the Pharmacist's Letter/Prescriber's Letter article.

Most clinical studies have used a specific extract of saw palmetto berry containing 80-90% fatty acids. Encourage patients who want to use saw palmetto to use a product that contains this type of formulation. It's similar to Super Saw Palmetto (Enzymatic Therapy), ProstaPro (Phytopharmica), Standardized Saw Palmetto Extract (Nature's Way), and others.

Saw palmetto is generally well-tolerated with few side effects. Dizziness and gastrointestinal complaints such as nausea, vomiting, constipation, and diarrhea occasionally occur.^6751,6762 There is a single case report associating saw palmetto with intraoperative hemorrhage, but episodes of bleeding or coagulation abnormalities have not been reported in clinical studies.⁸⁶⁵⁹

Tell men with BPH who want to try saw palmetto to get a urological exam first to rule out more serious conditions such as prostate cancer. Explain that taking a saw palmetto extract 320 mg daily might relieve BPH symptoms about as well as the prescription drug finasteride for some patients. Tell patients that there is no reason to take saw palmetto to prevent BPH or to "maintain urinary health."

View brands containing:
-	Saw palmetto

Question #1
For treating BPH, saw palmetto
	a. is more effective in combination with prescription BPH drugs.
	b. is similarly effective as finasteride (Proscar) for controlling BPH symptoms.
	c. frequently causes erectile dysfunction.
	d. lowers PSA levels, making prostate cancer monitoring difficult.

Question #2
Men with symptoms of BPH should
	a. increase sexual activity to "exercise" the prostate.
	b. take a weight loss supplement containing bitter orange to lose weight.
	c. receive counseling about safe sex.
	d. be evaluated to rule out prostate cancer.

Antiproliferatives and Growth Inhibiting Supplements

Pygeum, also known as African plum tree, is tried for BPH. It's used alone or in combination with saw palmetto or other natural products.

It's thought to be helpful for BPH due to antiproliferative and anti-inflammatory effects. There's preliminary evidence that pygeum suppresses epithelial growth factor (EGF). This might help shrink prostate epithelial cells.¹¹²²⁶ Pygeum might also inhibit other growth factors...basic fibroblast growth factor (bFGF)...insulin-like growth factor (IGF). Inhibiting these growth factors might inhibit prostate growth and hyperplasia.⁴³⁰¹ Pygeum may also have anti-inflammatory activity...it decreases production of leukotrienes and other 5-lipoxygenase metabolites.^10425,10426

Pygeum seems to decrease nocturia, increases peak urine flow, and reduce residual urine volume in men with BPH.^{3902,3903,3904,4302,6368,10425,10426}

Tell patients that pygeum extract 75-200 mg daily will probably help for BPH. But it's not known if it is any more effective than standard treatments or what its long term safety is. Pygeum is very well tolerated...the most common side effect is GI upset.¹⁰⁴²⁶

Stinging nettle root is widely used in Germany for BPH. Stinging nettle root seems to have an antiproliferative effect on prostatic cells.^11227,11229 It may also lessen the effects of androgenic hormones.¹¹²²⁸

There's some preliminary scientific support for using stinging nettle root in men with BPH.^6763,11230 But it's too soon to recommend.

Beta-sitosterol is a plant's version of cholesterol. It's found in many foods and herbs used for BPH. Beta-sitosterol is thought to be beneficial for BPH patients because it seems to have antiproliferative effects on prostate tissue.¹¹²³⁴

Beta-sitosterol significantly improves urinary symptoms. It increases maximum urinary flow and decreases the volume of urine left in the bladder. Like saw palmetto, beta-sitosterol does not affect prostate size.^{5327,5328,5329,7198}

Beta-sitosterol is also used to lower cholesterol. It is an ingredient in the cholesterol-lowering margarine Take Control. Take Control contains 1120 mg beta-sitosterol per tablespoon.⁵⁴⁴³

African wild potato (also known as South African star grass), pumpkin seed, and soy are plant-based sources of beta-sitosterol. Clinical studies of beta-sitosterol for BPH have used 60-195 mg per day.^{5327,5328,5329,6777,7198,
11231}

Practice Pearl

African wild potato might have a hypoglycemic effect.¹¹²³⁶ To be safe, tell patients with diabetes to monitor their blood sugar closely if they use products containing African wild potato.

Tell men, particularly those with elevated cholesterol, who are interested in beta-sitosterol for BPH that it is worth a try. Keep in mind that if beta-sitosterol margarine is used, other fat in the diet should be reduced accordingly to prevent weight gain.

Practice Pearl

Soy contains beta-sitosterol as well as the isoflavone genistein. Genistein seems to inhibit the growth of BPH cells.¹¹²³⁸ It's too soon to recommend soy specifically for BPH, but including it in the diet might have other health benefits, such as lowering cholesterol.

Like soy, red clover contains isoflavones. Red clover might relieve BPH symptoms by an anti-androgenic effect.¹¹²³⁹ It seems to increase the natural death of prostate cells rather than decreasing cell proliferation.¹¹²⁴⁰

Red clover isoflavones might decrease nocturnal urinary frequency and improve quality of life in men with BPH. However, red clover isoflavones do not seem to affect urine flow rate, prostate-specific antigen (PSA) values, or prostate size.⁶¹²⁸

Red clover for BPH looks promising, but it's too soon to recommend it.

Lycopene, a constituent of tomatoes and other red or pink fruits and vegetables, is widely advertised for "prostate health." Lycopene does seem to reduce proliferation of prostatic epithelial cells and decrease the risk of prostate cancer.¹¹²³⁷ But there's no credible evidence that lycopene supplements are beneficial for treating or preventing BPH. For patients interested in lycopene for BPH, suggest increasing intake of lycopene-containing foods, such as tomato-based sauces.

Men may ask about vitamin E for BPH prevention or treatment. Preliminary research suggests that vitamin E might have an antiproliferative effect on BPH cells.¹¹²³⁵ Limited clinical research of vitamin E in combination with rye grass pollen, saw palmetto, and beta-sitosterol indicates this combination might help BPH symptoms.¹¹²⁴¹ But there's no reliable evidence that vitamin E alone is effective for BPH prevention or treatment. Remind patients that the recent buzz about vitamin E deals with its possible ability to decrease the incidence of PROSTATE CANCER not BPH.^3959,11289

Question #3
What advice should you give a man with a normal exam, urinary analysis, and PSA level who wants to use saw palmetto for his BPH symptoms?
	a. Saw palmetto interacts with many drugs, including prescription drugs for BPH.
	b. Saw palmetto has sex-enhancing side effects.
	c. Saw palmetto acts slowly. It may take 1-2 months for symptom improvement.
	d. Saw palmetto sometimes causes excessive sweating and feeling of warmth.

View brands containing:
-	Pygeum
-	Stinging nettle root
-	Beta-sitosterol

Question #4
Possible concerns about pygeum for BPH include:
	a. frequency of drug interactions
	b. dizziness, orthostatic hypotension, and syncope
	c. in-vitro stimulation of prostate cancer cell growth
	d. unknown long-term safety

View brands containing:
-	African wild potato
-	Pumpkin seed
-	Soy

Question #5
In addition to improving BPH symptoms, beta-sitosterol can
	a. cause weight loss.
	b. lower postprandial blood glucose levels.
	c. reduce cholesterol.
	d. relieve constipation.

Question #6
Which of the following may affect BPH symptoms via its beta-sitosterol content?
	a. Soy
	b. African wild potato
	c. Pumpkin seeds
	d. All of the above

View brands containing:
-	Red clover
-	Lycopene
-	Vitamin E

Anti-inflammatory Supplements

Rye grass pollen extract contains beta-sterols. It seems to relax urethral smooth muscle tone and increase bladder muscle contractility. It might affect alpha₁-adrenergic receptors and relax both the internal and external bladder sphincter muscles.⁸¹⁷⁶ It might also decrease inflammation by inhibiting the biosynthesis of prostaglandins and leukotrienes.⁵²⁹⁸

Rye grass pollen extracts seem to improve BPH symptoms...frequency, nocturia, urgency, decreased urine flow rate, dribbling, and painful urination in men with mild to moderate BPH.^{5292,5293,5294} It may also decrease prostate size, improve urinary flow, and decrease residual urine volume. But not all research has shown effects on objective BPH measures.^{5292,8176,8520}

Rye grass pollen extract is sold as a prescription drug throughout Western Europe, Japan, Korea, and Argentina.⁸¹⁷⁶ Tell patients that rye grass pollen extracts appear to be safe and effective for up to 6 months. Cerniltion is the brand of rye grass pollen extract used in most clinical studies.^{5292,5293,5294,8176,8520}

Practice Pearl

Rye grass pollen extract is unlikely to cause allergic reactions in men with allergy to rye grass pollen. During the extraction process of the brand Cernilton, allergens are removed.⁵²⁹² Allergic reactions to rye grass pollen extract have not been reported in clinical trials.⁸¹⁷⁶

View brands containing:
-	Rye grass pollen

Miscellaneous

Garlic is sometimes used for BPH. There is preliminary evidence that it might be helpful for improving urinary flow, decreasing urinary frequency, and other symptoms associated with BPH or prostate cancer, according to preliminary clinical research.¹⁰³⁷⁴ But it's too soon to recommend garlic for BPH.

A variety of herbs including prickly pear cactus (Opuntia ficus-indica), fireweed (Epilobium angustifolium), buchu (Agathosma betulina), uva-ursi (Arctostaphylos uva-ursi), flaxseed oil (Linum usitatissimum) are sometimes used for BPH. But there's no reliable clinical research to support their use.

Minerals such as selenium and zinc are sometimes promoted for prevention or treatment of BPH. But there are no reliable clinical trials showing that either selenium or zinc is beneficial for BPH. In fact, population research suggests that a diet high in zinc might increase the risk of BPH.⁶⁹⁰⁸

Herbs and Supplements that Might Adversely Affect BPH¹¹²⁴²
Products with sympathomimetic effects may make urination more difficult. Sympathomimetics increase muscle tone of the prostate stroma, causing the prostate to contract around the urethra. They may also cause contraction of the internal bladder sphincter.
Bitter orange	Ephedra
Country mallow	Yohimbe

Products with anticholinergic effects can also make urination more difficult. Anticholinergics decrease the ability of the bladder detrusor muscle to cause bladder contraction.
Henbane	Scopolia
Jimson weed	Wild lettuce

Products with hormonal activity can accelerate prostate enlargement.
Androstenediol	Dehydroepiandrosterone (DHEA)
Androstenedione	Pregnenolone

View brands containing:
-	Garlic
-	Prickly pear cactus
-	Fireweed
-	Buchu
-	Uva-ursi
-	Flaxseed oil
-	Selenium
-	Zinc

Question #7
It's too soon to recommend which of the following for BPH?
	a. Stinging nettle root
	b. Red clover
	c. Vitamin E
	d. All of the above

Question #8
Which of the following supplements have good evidence to support recommendation for BPH?
	a. Beta-sitosterol
	b. Lycopene
	c. Selenium
	d. Zinc

The Bottom Line

Saw palmetto is perennially one of the best selling herbal products worldwide. It appears to be as effective as finasteride for BPH symptoms. Unlike finasteride, saw palmetto doesn't usually cause sexual dysfunction and doesn't affect PSA levels. It's unclear whether alpha₁-blockers are superior to saw palmetto, but they appear to have a faster onset of effect.

Pygeum is also well-studied for BPH symptoms. As a single agent, it appears to decrease nocturia, increase urine flow, and decrease residual urine volume. It hasn't been compared to conventional BPH drugs.

Beta-sitosterol is a constituent of many herbal products for BPH. It hasn't been compared with conventional BPH drugs, but appears to reduce BPH symptoms. Beta-sitosterol as a supplement or as beta-sitosterol margarine is a good choice for men with hypercholesterolemia.

African wild potato appears to help BPH symptoms, most likely because of its high beta-sitosterol content. Preliminary research suggests it may lower blood glucose, but this hasn't been reported in clinical studies. Tell men who want to try African wild potato to monitor blood sugar closely if they have diabetes.

Rye grass pollen extract also contains beta-sitosterol. There's good research to support its use. Whether it works as well as finasteride or alpha₁- blockers is unknown. It's used widely as a prescription drug in Europe, Japan, and other countries.

Stinging nettle root and pumpkin seed are sometimes added to combination BPH products. Although there's some research suggesting these might help BPH symptoms, more evidence is needed before they can be recommended.

A lot of people are interested in isoflavones, such as those found in soy and red clover, for BPH. Tell men there's some preliminary research that looks interesting, but it's too soon to recommend isoflavones for BPH.

People may ask about supplements such as garlic, lycopene, vitamin E, selenium, and zinc. There's a lot a research going on to see if these supplements are useful for treating or preventing prostate cancer. Remind patients that BPH does not predispose men to prostate cancer. So far, there's no reliable clinical evidence that any of these supplements can prevent or treat BPH.

Combination therapy with alpha₁-antagonists and finasteride may work better than either drug alone.¹¹²⁸⁹ But combining saw palmetto with conventional prostate drugs doesn't seem to improve effectiveness. A combination of rye gras pollen, saw palmetto, beta-sitosterol, and vitamin E seems to help BPH symptoms, but the combination hasn't been compared to individual ingredients or conventional prostate drugs.¹¹²⁴¹

Natural products that are commonly used for BPH all appear to be reasonably safe. There's also no evidence of serious drug interactions. More research is needed to determine the long-term effectiveness and safety of natural products for BPH.

Most natural products appear to work either by anti-inflammatory or antiproliferative activity, or by 5-alpha reductase inhibition, resulting in slow onset of activity. Tell men it may take at least several weeks to a couple of months for any noticeable effect from natural products.

For men who want to try natural medicines for treating BPH, recommend single-ingredient products such as saw palmetto, pygeum, beta-sitosterol, or rye grass pollen extract. The product should be taken at adequate doses for a trial of 1-2 months to determine its effectiveness for the patient's symptoms.

Recommendation Chart for Natural Medicines Used for BPH *

Likely
Safe

Possibly
Safe

Insufficient
Evidence

-	Beta-sitosterol

-	Saw palmetto

Pygeum

Possibly
Effective

-	Rye grass pollen

-	African wild potato

Insufficient
Evidence

-	Flaxseed oil

Lycopene

-	Prickly pear cactus

-	Red clover

Uva-ursi

Possibly
Ineffective

-	Pumpkin seed

-	Stinging nettle root

-	Stinging Nettle

Likely
Ineffective

Ineffective


KEY:
	Consider recommending this product.

	Don't recommend using this product.

	Recommend against using this product.

* These proposed recommendations are based solely on the Safety and Effectiveness Ratings contained in Natural Medicines Comprehensive Database. This assumes use of high-quality, uncontaminated products and the use of typical doses. Keep in mind that some products are never appropriate for some patients due to concomitant disease states, potential drug interactions, or other clinical factors. Use your clinical judgment before recommending any product.

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6763

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6764

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6765

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6769

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6770

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6771

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6772

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6773

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6775

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6776

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6777

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