Benign prostatic hyperplasia (BPH) is a common enlargement of the prostate gland as a man ages. Though the prostate continues to grow during most of a man’s life, the enlargement doesn’t usually cause symptoms before age 40, but more than half of men in their sixties, and as many as 90 percent in their seventies and eighties have some symptoms of BPH. These are typically referred to as lower urinary tract symptoms (LUTS), and include incomplete bladder emptying, frequent urges to urinate during the day and at night. However, it should be understood that LUTS and BPH are not equivalent. While all BPH includes LUTS, not all LUTS are reflective of BPH.

Lifestyle and LUTS

This is comprehensively explained in a peer-review article from Current Opinion in Urology.¹ The authors of the article explain that LUTS has also been associated with many factors, including diet—which is unrelated to the prostate directly but which is reflective of various lifestyle factors. The article indicates that:

• Increased total calorie intake has been associated with LUTS;
• Red meat, fat, cereals, bread, poultry and starch have been associated with increased risks of symptomatic LUTS;
• Total protein, dairy, vegetables, fruits, polyunsaturated fatty acids, linoleic acid, carotenoids, vitamins A, C and D have been associated with decreased LUTS;
• Lower vitamin D status and caffeine intake were associated with a greater prevalence of LUTS;
• Higher serum levels of vitamin E, lycopene, selenium and carotene have been associated with reduced LUTS.

Vitamin D and LUTS
This relationship between vitamin D and LUTS was demonstrated in the National Health and Nutrition Examination Survey, where a majority of men with LUTS (89 percent) had insufficient vitamin D levels. In fact, 55 percent had deficient vitamin D levels. Among the 1388 men (58 percent) with LUTS data and vitamin D levels, 48 percent had at least one LUTS. The researchers concluded, “Vitamin D insufficiency and deficiency are highly prevalent among adult men in the U.S., and vitamin D deficiency is associated with moderate-severe UI and the presence of at least one LUTS.”²

Additional non-BPH disease states and LUTS Additional research has similarly demonstrated that other non- BPH, non-disease states are associated with LUTS:

While many men who experience LUTS symptoms do have BPH, those same symptoms may occur as the result of lifestyle factors, independently of BPH. Consequently, it makes sense to get a proper diagnosis of your symptoms. Also, assuring adequate vitamin D intake (2,000 IU daily recommended), while eating a good diet and exercising, while avoiding constipation, smoking and the overconsumption of alcohol, may also help you to avoid LUTS or even help reduce those symptoms in some instances. Of course if you do have BPH, there are nutraceuticals, which can help. Refer to “Naturally Improving Prostate Health” in the May 2016 issue of Total Health.

References:

1. Lin PH, Freedland SJ. Lifestyle and lower urinary tract symptoms: what is the correlation in men? Curr Opin Urol. 2015 Jan;25(1):1-5.
2. Vaughan CP, Johnson TM 2nd, Goode PS, et al. Vitamin D and lower urinary tract symptoms among US men: results from the 2005–2006 National Health and Nutrition Examination Survey. Urology. 2011; 78(6):1292–7.
3. Thurmon KL, Breyer BN, Erickson BA. Association of bowel habits with lower urinary tract symptoms in men: findings from the 2005-2006 and 2007-2008 National Health and Nutrition Examination Survey. J Urol. 2013 Apr;189(4):1409-14.
4. Marshall LM, Holton KF, Parsons JK, Lapidus JA, Ramsey K, Barrett-Connor E; Osteoporotic Fractures in Men (MrOS) Study Group. Lifestyle and health factors associated with progressing and remitting trajectories of untreated lower urinary tract symptoms among elderly men. Prostate Cancer Prostatic Dis. 2014 Sep;17(3):265-72.
5. Erickson BA, Vaughan-Sarrazin M, Liu X, Breyer BN, Kreder KJ, Cram P. Lower urinary tract symptoms and diet quality: findings from the 2000-2001 National Health and Nutrition Examination Survey. Urology. 2012 Jun;79(6):1262-7.
6. Fowke JH, Phillips S, Koyama T, Byerly S, Concepcion R, Motley SS, Clark PE. Association between physical activity, lower urinary tract symptoms (LUTS) and prostate volume. BJU Int. 2013 Jan;111(1):122-8. BJU Int. 2013 Jan;111(1):122-8.
7. Suh B, Shin DW, Hwang SS, Choi HC, Kwon H, Cho B, Park JH. Alcohol is longitudinally associated with lower urinary tract symptoms partially via high-density lipoprotein. Alcohol Clin Exp Res. 2014 Nov;38(11):2878-83.
8. Joseph MA, Harlow SD, Wei JT, Sarma AV, Dunn RL, Taylor JM, James SA, Cooney KA, Doerr KM, Montie JE, Schottenfeld D. Risk factors for lower urinary tract symptoms in a population-based sample of African-American men. Am J Epidemiol. 2003 May 15;157(10):906-14.

The prostate is an important male gland that secretes a fluid found in semen.¹ In addition, the urethra (the tube through which urine flows) runs through the prostate, so changes in prostate structure, such as prostate enlargement, can profoundly and negatively affect urinary function. The most common issue that impacts prostate health for most men is benign prostatic hyperplasia. A more serious, common issue is prostate cancer. This article will review these problems, and consider some key nutraceuticals that may help.

The prerequisites for developing benign prostate hypertrophy (BPH) are the presence of testes and age. It is one of the most frequently occurring diseases in men over 60 years of age. According to the National Institute of Health (NIH), BPH affects more than 50 percent of men over the age of 60 and as many as 90 percent of men over the age of 70. This translates to a staggering 4.5 million visits to a physician for BPH in the United States in 2000.¹

What are the symptoms?
In the initial stages, a patient may experience increased urinary frequency during the day, nocturia (getting up at night to go to the toilet) and the sensations of not being able to empty completely. As the condition becomes more advanced, there is an increase in the obstructive symptoms characterized by the following: weak urine stream, difficulty starting urination, straining to urinate, stopping and starting again while urinating, dribbling at the end of urination, urgency, and pain on urination. If the BPH symptoms are severe, it may result in the inability to urinate. This can cause severe pain and discomfort. In addition, if urine is retained in the bladder for long periods of time, this can lead to urinary tract infections, bladder or kidney damage, or bladder stones.³

What is the primary risk factor?
It appears that age itself is the primary risk factor for developing symptoms associated with BPH.

Is there a link between hormonal changes during aging and benign prostate hypertrophy?

The exact cause of BPH is unclear, although researchers believe it may be caused by hormonal changes that occur during the aging process.

• Decreased testosterone levels: One theory is that as a man ages, the amount of testosterone in his blood decreases, leaving a higher proportion of estrogen in his blood. The disproportion of estrogen may contribute to cell growth within the prostate gland.
• Increased levels of dihydrotestosterone (DHT): Another possible theory is that as a man ages there is a hormonal change involving the accumulation of DHT, a by-product of testosterone in the body. If levels of DHT accumulate in the prostate,
• overgrowth of cells in the prostate can occur.³

What are the possible treatments?
Treatment for BPH depends on the severity of symptoms. Medications are the most common way to control mild to moderate symptoms of BPH. Watchful waiting, also known as observation, expectant therapy or deferred therapy, is often the preferred approach for men with mild symptoms who aren’t bothered by them.

—Pharmaceutical Medications
The most commonly used medications are alpha-adrenergic blocking agents which work by relaxing the smooth muscle tissue. Since there is a large number of alpha-adrenergic receptors in the bladder, the bladder neck and prostate gland, they cause relaxation and reduced tone, which then allows urinary flow. Although these drugs have been found to be effective, patients may experience side effects including headache, dizziness, low blood pressure, fatigue, weakness, and difficulty breathing. These are due to the fact the drug works on all smooth muscle tissue in the body, not just the prostate. The long-term risks and benefits have not been studied.&sup4;

The other common drug treatment is enzyme (5-alpha reductase) inhibitors that work directly on the endocrine system. They prevent the conversion of testosterone to the hormone dihydrotestosterone (DHT) and as a result reduces the size of the prostate itself. However, while studies have shown a decrease in symptoms it does not correlate with urinary flow rate and volume. In many cases, a treatment period of six months is necessary to see if the therapy is going to work. The side effects include reduced libido, impotence, breast tenderness and enlargement, and reduced sperm count. Again, these effects are due to the fact the drug may reduce the total testosterone in the body and the effects are not restricted to the prostate gland. The long-term risks and benefits have not been studied.

—Surgical Treatment Most doctors recommend removal of the enlarged part of the prostate as the best long-term solution for patients with BPH. With surgery for BPH, only the enlarged tissue that is pressing against the urethra is removed; the rest of the inside tissue and the outside capsule are left intact. Surgery usually relieves the obstruction and incomplete emptying caused by BPH.1 Surgery used to be the most common way to treat BPH. Today, its use is declining because of new medications and minimally invasive treatments. Surgery is usually used when non-surgical treatments fail or if there are BPH complications.²

—Complementary Medicines The principle goal of BPH treatment is to reduce excessive cell growth by inhibiting the conversion of testosterone into the more potent hormone dihydrotestosterone (DHT) and so preventing estrogen from attaching to receptors in prostate tissue.

Some supplements are intended to reduce symptoms while others will provide nutritional support. The combination of glycine, alanine, and glutamic acid can reduce urinary urgency, urinary frequency, and delayed micturition (initiation of flow). Beta-sitosterol may also help reduce symptoms of BPH. Betasitosterol also lowers cholesterol, which is important since high cholesterol levels can contribute to prostate hypertrophy. Flaxseed oil is a good source of the essential fatty acid (EFA) alphalinolenic acid (an omega-3 fatty acid). It is well-known that zinc is an important mineral for male health. Why? It may be related to the fact that zinc inhibits 5 alpha reductase and therefore lowers DHT production.

The most well studied herb is saw palmetto (Serenoa serrulata). Saw palmetto is a 5-alpha reductase inhibitor that inhibits the conversion of testosterone to DHT in the prostate, has an antiestrogenic effect, and helps improve all symptoms of BPH. Both pygeum (Pygeum africanum) and stinging nettles (Urtica dioica) may also reduce BPH symptoms although research is less conclusive.

Latest research— UrologicPros
One of the most recent exciting breakthroughs in this area has been the development of a unique herbal and mineral preparation, UrologicPros™, which has been clinically proven to be effective in reducing the urinary symptoms associated with BPH.

UrologicPros contains a patented formulation of herb ingredients, crateva and horsetail, which has been shown to be effective in treating the symptoms of overactive bladder in men and women with urinary incontinence. In this formulation, it has been combined with saw palmetto, zinc and selenium, which support prostate health.

In the most recent study, 33 men were asked to take UrologicPros (as an oral supplement) each day for a period of three months. Symptoms were assessed using a diary of urinary frequency (day and night) and the International Prostate Symptom Score.

There was a significant gradual reduction in daytime urinary frequency over the three months, for those with moderate and severe symptoms. There was also a significant reduction in episodes of nocturia over the three months.

There was an overall 40 percent reduction in symptoms over the three months. The median reduction (of individual results) was 45 percent with a range from (0–81 percent improvement). The greatest improvement was seen relating to nocturia, and urinary flow (particularly the symptom “difficulty emptying bladder”). The positive effect of the treatment on nocturia was seen within the first month, whereas the urinary flow symptoms improved most significantly after two months of treatment. There was also a significant improvement in quality of life reported as well. At completion of the study, 29 of the 33 subjects (88 percent) wanted to continue with treatment.

Figure 1: Average daytime urination frequency after treatment with UrologicPros

Figure 2: Average episodes of nocturia after treatment with UrologicPros

The inclusion of whole, fresh, unrefined, and unprocessed foods including fruits, vegetables, whole grains, soy, beans, seeds, nuts, olive oil, and cold-water fish (salmon, tuna, sardines, halibut, and mackerel) may help. It is important to remember that eating organic food helps reduce exposure to hormones, pesticides, and herbicides (which affect testosterone and estrogen balance). Optimal hormonal balance will occur in the absence of refined sugar and flour, dairy products, refined foods, fried foods, junk foods, and hydrogenated oils. There will be less stress on the bladder system itself if the amount of alcohol (particularly beer), and caffeine in the diet is reduced.

In summary, at present we have a limited understanding of the pathology underlying the symptoms associated with an enlarged prostate as men age. There are no specific pharmacological medications specific for the prostate (or drugs that do not have unwanted side effects in the body). Based on its current success rate, surgery should always be considered a last option when all other treatments have failed. However, there is increasing research directed at the role for individual and combined nutraceuticals in the management of urinary tract problems including BPH. Therefore, natural treatments should be considered as the first line of defense on the treatment of benign prostate hypertrophy.

Elizabeth Steels, Ph.D. is the research director for Applied Science and Nutrition, an Australian based research organization. Elizabeth is a clinical nutritionist with over 15 years in clinical research, natural health and education.

References
1. 1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, NIH Publication No. 04–3012, Prostate Enlargement. http//kidney.niddk.nih.gov/kudiseases/pubs/prostate enlargement/index.htm#gland#gland
2. 2. Mayo Clinic. Enlarged prostate (BPH) guide. www.mayoclinic.com/health/enlarged-prostate-bph/BP99999/PAGE=BP00016
3. 3. E Drug digest. Begin Prostate Hypertropy. www.drugdigest.org/DD/HC/Treatment/0,4047,550246,00.html&e=14911
4. 4. Urology Channel. Prostate. www.urologychannel.com/prostate

The prostate is a walnut-sized gland that produces semen, the fluid that transports sperm. After a man turns 50, or in those with urinary symptoms, the prostate may begin to need support. And men who have CFS/FMS can be particularly vulnerable to a form of prostate irritation called prostadynia.

The prostate rings the urethra, the tube that transports ejaculate and drains urine from the bladder. As the prostate expands in size, the urethra may be squeezed and narrowed, causing urinary symptoms such as frequent urination (particularly during the night), urgency, difficulty starting the stream, a weaker stream, dribbling at the end, and incomplete emptying.

As pointed out last year in a review of pollen extract for prostate support, benign prostatic hyperplasia (BPH, formerly called hypertrophy), involves a renewed growth in the number of prostate cells late in life.¹ Unfortunately, of men between the age of 40 and 59, nearly 60 percent can be shown to already be suffering from benign prostatic hyperplasia. This usually does not present a noticeable problem until after the age of 50; by the age of 80, however, some 85 percent of all men suffer from one or more symptoms of BPH. The primary effect of BPH is a progressive decrease in the ability to empty the bladder as the prostate enlarges and applies pressure to the urethra.

BPH is hardly the lone prostate and sex hormone related issue that can be troubling to men. Aside from prostate cancer, which for most men is so slow growing as to not be life threatening, many men are concerned about low testosterone, which has its own repercussions. Two of the repercussions of low testosterone are a low level of muscle-maintaining free testosterone and elevated levels of estrogen produced from testosterone by a pathway referred to as the aromatase pathway. Fortunately, there are a number of safe natural compounds that can help to regulate both sides of this equation.

Protective herbs and nutrients have counterparts that increase the risks of various conditions. Some of these potentially damaging compounds are prescriptions given for unrelated conditions and this provides a rationale for being cautious about prescription drugs. What you do not know definitely can hurt!

PROTECTIVE AND SUPPORTIVE NUTRIENTS AND HERBS

Omega-3s
In 2013, experts slammed a claimed fish oil/omega-3 fatty acid intake link to prostate cancer as “scaremongering.” The trial in question purported to find increased risks for total prostate cancer as well as increased risks of both low-grade and high-grade prostate cancer, an increase of 71 percent in this latter category.² The responses were quick and brutal. One nutritionist (Duffy MacKay, vice president of scientific and regulatory affairs at the for Responsible Nutrition (CRN)) pointed out, quite correctly, that the findings of this study were based on blood level differences so small that “[t]his change [of 0.2%] literally could have occurred if somebody ate a fish sandwich on their way to get their blood drawn.”³ Both the consumers of the low and the high levels of long chain omega-3 fatty acids were within the normal blood range.

Others pointed out that the findings of the study clearly imply that men in countries with high levels of consumption of seafood, such as Scandinavia and Japan, should exhibit high levels of prostate cancer, yet the opposite is the case. Alan Ruth, PhD, CEO of the Irish Health Trade Association observed, “[i]n a 2010 meta-analysis of 31 studies published in the American Journal of Clinical Nutrition, the risks of prostate cancer diagnosis calculated for high fish consumption ranged from a 61% decrease in risk to a 77% increase in risk, and several showed no significant differences in risk at all…In the same meta-analysis, pooled data from four studies on fish consumption and death from prostate cancer (rather than diagnosis of prostate cancer) found a 63% decrease in risk for high fish consumption.”⁴

Especially interesting in this dust-up is the recent attempt to rehabilitate omega-6 fatty acids. In pre-modern times, the intake of omega-3 to omega-6 fatty acids in the diet typically was in the range of one-to-two, whereas today in the United States it regularly may be as low as one-to-twentyfive, with prostate cancer rates climbing steadily over the last 60 years. In this instance, a headline is revealing: “Corn oil, omega-6 could speed up prostate cancer.”⁵ Journal article titles are more prosaic, yet just as damning: “A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer.”⁶

Barry Sears, who has written for years on the health effects of fatty acids, both good and bad, tartly comments in his blog, “Omega-3 fatty acids and prostate cancer? Oh, really?”⁷ Among other things, Sears demonstrates how easily a statistically significant blood reading of fatty acid profiles can be attached to otherwise clinically irrelevant findings. The take away message in this case is that the experience around the world repeatedly has been that prostate risks, especially death from prostate cancer, are lower in matched populations that consume more fish. There is nothing in recently published research that should make us doubt that improving the omega-3 to omega-6 ratio in our diets is a good goal at which to aim.

Grape Skin Extract & Resveratrol
In many areas in the US and the United Kingdom (Scotland has not yet opted out of the Union), one cannot visit a doctor without being queried about alcohol intake and then the required lecture on the evils of alcohol. The distinction as to the source of alcohol in the diet routinely drops out despite the fact that red wine has been recognized in Europe for centuries as exhibiting various health benefits and little downside as long as consumed in moderation. It turns out that red wine, often thought of in terms of the heart, may benefit the prostate, as well.

The trick to the studies is that the researchers must work vigorously to screen for the different sources of alcohol over the course of a man’s life. If this is done, then the research is likely to confirm that a glass of red wine per day may be protective against the risk of prostate cancer.⁸ Less clear is which compounds in red wine are protective. Perhaps many are. A recent study on grape skin extract and resveratrol identified several protective mechanisms of action.⁹ Some of the factors linked to resveratrol have been known for years, whereas other mechanisms and, similarly, the benefits of other red wine compounds, are being vigorously researched. Grape seed components (proanthocyanidins) are another example of a source of anti-cancer benefits.¹⁰ Given the huge volume of papers being published today on the healthprotective benefits of red wine and its ingredients, it is a reasonable conclusion that most men may benefit from one or two glasses of red wine per day consumed with meals.

^{Quercetin & EGCG}
The dietary bioflavonoid quercetin is well known to readers of this magazine, as is epigallocathechin gallate (EGCG). Both compounds are considered to be health protective and quercetin, in particular, is known to improve the uptake (bioavailability) and the benefits of many other compounds found in the diet and in herbs. Papers routinely show greater efficacy or even benefits where none initially were found, when quercetin is combined with resveratrol, with sulphorafane, with EGCG, etc. One of the more interesting recent findings is that these combinations sometimes not only can help to prevent the transformation of cells from precarcinogenic stages to active cancer, but also can interfere with or eliminate entirely cancer stem-cell characteristics. Cancer stem cells are the ultimate source of cancer self-renewal, so this action by the combination of quercetin and EGCG is a warm recommendation.¹¹

Bitter Melon
Bitter melon has received quite a bit of publicity recently with regard to pancreatic cancer. It would be unfortunate were the exploration to end there. Several researchers have reported that treatment of bitter-melon-related products in a number of cancer cell lines induces cell cycle arrest and apoptosis without affecting normal cell growth.¹² Researches targeted specifically at prostate cancer have demonstrated that the impact of bitter melon extends to this area.¹³ Admittedly, bitter melon is not a staple at the American table. Perhaps that should change. See my earlier article, “Going WILD with Bitter Melon for Blood Sugar Support.”¹⁴

Pomegranate
Pomegranate is a fruit long associated with healing and medicine. Indeed, the pomegranate is on the crest-of-arms of the British Royal Society of Medicine and of many other ancient organizations devoted to healing. A quick look at the PubMed database shows that the keywords “pomegranate” and “prostate” bring up 60 studies. Many of these studies have been promising, especially when pomegranate was added to other ingredients with related and differing mechanisms of action. For instance, in 2013 the polyphenol rich whole food supplement Pomi-T® (pomegranate seeds, green tea, broccoli, and turmeric) was reported to have a direct anti-cancer effect in men with prostate cancer.15 These results were confirmed in a larger clinical trial published in 2014.¹⁶

Thymoquinone and Black Seed
Few Americans have heard either of black seed or thymoquinone (TQ). The former is famous for healing in the areas in which it grows naturally, meaning much of the eastern Mediterranean through the Near and Middle East all the way to India. Mohammed is reputed to have said that the seed cures every condition except death itself.

With regard to the prostate, black seed is useful for both BPH and in preventing prostate cancer induction. One of the important ingredients in black seed oil, thymoquinone, promotes healthy apoptosis in prostate cells and therefore helps the body to regulate the size and health of the prostate.^17,18 Similar effects have been found in, for example, breast cancer, so TQ has a broad spectrum of applications.¹⁹

Cactus Flower
A couple of decades back, the herbal extract chrysin was introduced to the athletics and body building world as an answer to improving free testosterone levels and reducing the pathway (aromatase) that transforms testosterone to estrogen. Chrysin has some benefits, as long as one does not expect too much and is willing to focus on the anxiolytic qualities of the compound (found in passion flower). However, much more successful compounds for this purpose of increasing free testosterone, and so forth, have been found. One of these is an extract of cactus flower (Opuntia ficus-indica).

I ran across this almost a decade ago being sold in Germany and Israel for BPH,²⁰ but at the time could not find a reliable source of supply. Since then, a friend with whom I was working took this item and continued to dig until he found a reliable source that he could market as increasing serum free testosterone levels and reducing aromatase (reducing estrogen production and inhibiting the binding of dihydrotestosterone/DHT.) As my friend writes at his website, based on preliminary laboratory research, “Opuntia flower extract (1 mg/ml concentration) inhibited over 80% of the activity of 5-alpha reductase in human prostate tissue homogenate and inhibited over 80% of aromatase activity in human placenta tissue homogenate.”²¹ This particular product also contains supporting ingredients, such as an extract of stinging nettle root.

Some Prostate-Questionable Foods and Pharmaceuticals Now for a few items that men may want to remove from their daily habits or environment.

• Non-and low-fat milk (but not whole milk or other dairy products) intake by men is linked to higher rates of prostate cancer²²
• Long-term use of statins increases the risk of prostate cancer²³
• Oral contraceptive use is associated with prostate cancer—this refers to these contraceptives getting into the environment at large and not to use by one’s partner²⁴

Conclusion
There are protective foods, nutrients and herbs of which men should take advantage to maintain and regain prostate health as well as improve other parameters of health and performance. Omega-3 fatty acids and the active compounds found in red wine (grape skin anthocyanidins and other compounds, resveratrol, grape seed proanthocyanidins, quercetin), green tea (EGCG) and bitter melon are on this short list. More exotic are black seed and thymoquinone as well as cactus flower extract. For the most part, these can be characterized as special foods since they can be consumed over the long term and have few or no downsides even when consumed chronically in large amounts. Indeed, this should be the goal—a little prevention is always worth a whole lot of cure.

1. 1. F. Hinman, Benign Prostatic Hypertrophy. New York: Springer-Verlag, 1983.
2. 2. Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst. 2013 Aug 7;105(15):1132– 41. doi: 10.1093/jnci/djt174.
3. 3. Experts slam omega-3 link to prostate cancer as overblown ‘scaremongering.’ http://www.nutraingredients.com/content/view/print/796071
4. 4. Ibid.
5. 5. http://www.foodnavigator-usa.com/news/printNewsBis.asp?id=65537
6. 6. Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutr Res. 2011 Jan;31(1):1–8. doi: 10.1016/j.nutres.2011.01.002.
7. 7. http://zonediet.com/blog/2013/07/
8. 8. A glass of red wine a day keeps prostate cancer away? http://nutraingredients.com/news/printNewsBis.asp?id=54898
9. 9. Hudson TS, Hartle DK, Hursting SD, Nunez NP, Wang TT, Young HA, Arany P, Green JE. Inhibition of prostate cancer growth by muscadine grape skin extract and resveratrol through distinct mechanisms. Cancer Res. 2007 Sep 1;67(17):8396–405.
10. 10. Raina K, Singh RP, Agarwal R, Agarwal C. Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice. Cancer Res. 2007 Jun 15;67(12):5976-82.
11. 11. Tang SN, Singh C, Nall D, Meeker D, Shankar S, Srivastava RK. The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J Mol Signal. 2010 Aug 18;5:14. doi: 10.1186/1750–2187–5–14.
12. 12. Nerurkar P, Ray RB. Bitter melon: antagonist to cancer. Pharm Res. 2010 Jun;27(6):1049–53. doi: 10.1007/s11095–010–0057–2.
13. 13. Ru P, Steele R, Nerurkar PV, Phillips N, Ray RB. Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model. Cancer Prev Res (Phila). 2011 Dec;4(12):2122–30. doi: 10.1158/1940–6207.
14. 14. http://www.totalhealthmagazine.com/articles/vitamins-and-supplements/going-wild-with-bitter-melon-for-blood-sugar-support.html
15. 15. Goodman A. High Marks for Nutritional Supplement in Patients with Localized Prostate Cancer. Value-Based Cancer Care. September 2013 Vol 4, No 7. http://issuu.com/vbcc/docs/vbcc_september_2013_digital/50
16. 16. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. A doubleblind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer-the UK NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014 Mar 11. doi: 10.1038/pcan.2014.6.
17. 17. Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP. Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res. 2007 Aug 15;67(16):7782–8.
18. 18. Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012 Feb 15;83(4):443–51. doi: 10.1016/j.bcp.2011.09.029.
19. 19. Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, Das SK, Emdad L, Sarkar D, Fisher PB, Mandal M. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013 Apr 17;8(4):e61342. doi: 10.1371/journal.pone.0061342.
20. 20. Palevitch D., Earon G., Levin I., Treatment of benign prostatic hypertrophy with Opuntia ficus-indica (L.) Miller. Journal of herbs, spices & medicinal plants. J. herbs spices med. plants 1993;2(1):45–49.
21. 21. http://cleanmachineonline.com/science/how-it-works/ drawing upon Jonas A, Rosenblat G, Krapf D, Bitterman W, Earon G, Neeman I. Efficacy of cactus flowers miller treatment in benign prostatic hyperplasia due to inhibition of 5a reductase activity, aromatase activity and lipid peroxidation. HerbaMed paper; undated. Available at: http://www.herbamed.com/Portals/0/articles/Opuntia.pdf.
22. 22. Park SY, Murphy SP, Wilkens LR, Stram DO, Henderson BE, Kolonel LN. Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study. Am J Epidemiol. 2007 Dec 1;166(11):1259–69.
23. 23. Chang CC, Ho SC, Chiu HF, Yang CY. Statins increase the risk of prostate cancer: a population-based case-control study. Prostate. 2011 Dec;71(16):1818–24. doi: 10.1002/pros.21401.
24. 24. Margel D, Fleshner NE. Oral contraceptive use is associated with prostate cancer: an ecological study. BMJ Open. 2011 Nov 14;1(2):e000311. doi:10.1136/bmjopen–2011–000311.