Resveratrol Background
Before jumping into a discussion about the fascinating human research, however, let’s take a moment to review just what resveratrol is, in case you’re unfamiliar with it. Resveratrol is a type of natural phenol by several plants in response to injury or attack by pathogens.^3,4 These plants include grapes, peanuts⁵ and Japanese Knotweed (Polygonum cuspidatum).⁶ Resveratrol helps provide protection to the plants, at least in part, due to its demonstrated antioxidant properties.⁷ These antioxidant properties benefit humans too, as shown in research where resveratrol provided a direct antioxidant effect against free radicals, and facilitated an increase in vitamin E⁸—another powerful antioxidant.

There are two primary isomers (i.e. two forms) of resveratrol, trans- and cis-. To be clear, trans-resveratrol has been unequivocally shown to have much greater activity than cis-resveratrol.⁹ Consequently, when purchasing a resveratrol product, make sure to check the supplement facts panel to verify that the product contains trans-resveratrol. If just”resveratrol” is listed, without the trans-designation, or if cis-resveratrol is listed, you would be better off choosing a different product that lists trans-resveratrol. In any case, for ease of reading, I will drop references to trans– in the rest of this article, although it can be assumed that any mention of resveratrol will actually refer to trans-resveratrol.

Cardiovascular Health
As its first claim to fame, resveratrol has been found to have activity that may have protective effects on the cardiovascular system. In both test-tube and animal research, resveratrol has been shown to inhibit platelet aggregation (i.e. the clumping together of blood platelets). This has value since excessive or inappropriate aggregation of platelets can lead to formation of blood clots and subsequent blockages in blood vessels that result in insufficient blood flow, heart attack or stroke.¹⁰ Resveratrol can also promote vasodilation (a relaxed and expanded state of the artery that accommodates increased blood flow) by enhancing the production of a naturally occurring substance in the body called nitric oxide.¹¹

More importantly, human clinical research¹² has demonstrated that 100 mg/day of resveratrol significantly reduced arterial stiffness (a major indicator of atherosclerosis) compared to placebo, and also lowered systolic blood pressure by 5.5 points in patients with type 2 diabetes. Another human study,¹³ which used a much higher dose (2.3 g) in older adults, found that resveratrol not only improved vascular function more than placebo, but also increased the number of mitochondria.those parts of the cells that help to generate energy for our body! Another interesting cardiovascular benefit is resveratrol’s effect on Apolipoprotein B (ApoB), a primary component of many lipoproteins such as LDL (the gbad cholesterolh) that are involved in atherosclerosis and cardiovascular disease. In human clinical research¹⁴ on overweight or obese individuals with mild hypertriglyceridemia, 1000 mg/day of resveratrol for one week followed by 2000 mg/day for two weeks reduced ApoB production rate by an impressive 22 percent. In addition, flow-mediated dilatation (a measure of arterial circulation and endothelial function) was increased in human studies^15,16,17 where 10 mg to 270 mg/day of resveratrol was given. In one of the studies,¹⁸ LDL cholesterol levels were also significantly decreased.

Inflammation
In addition to showing anti-inflammatory effects in in-vitro and animal studies, resveratrol has also been shown to comprehensively suppress oxidative and inflammatory stress with as little as 40 mg/day in normal human subjects.¹⁹ This included the reduction of inflammatory markers such as TNF-alpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.²⁰

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has also responded to treatment with resveratrol. In one study²¹ with 56 UC patients, those receiving 500 mg/day of resveratrol had significant symptom improvement, reduced malondialdehyde (a highly reactive oxidative stress compound), and increased superoxide dismutase (SOD), and total antioxidant capacity. In another human study²² with 50 UC patients, 500 mg/day of resveratrol also reduced the activity of inflammatory compounds, including TNF-α, hs-CRP, and activity of NF-κB. Furthermore, in a study²³ of firefighters, supplementation with 100 mg/day resveratrol for 90 days, plasma biomarkers of inflammation were reduced after a physical fitness test, including IL-6 and TNF-α. This adds further credence to resveratrol’s anti-inflammatory effects.

Immune Health/Breast Cancer Prevention
Resveratrol’s effect on immune health can be as fundamental as increasing certain circulating immune cells, or as profound at reducing the risk of breast cancer. For example, human research²⁴ was conducted to assess the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy individuals. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells (functioning as a first line of defense and a bridge between innate and adaptive responses) and regulatory T cells—demonstrating that resveratrol has clear biological effects on human circulating immune cells.

With regard to breast cancer prevention, resveratrol may help in a couple of ways. First, resveratrol has been shown to have a dose-dependent effect on reducing the formation of mammary tumors in-vitro as a result of down-regulating DNA methyltransferases. To see if it had a similar effect in humans, a study²⁵ was conducted in which 39 adult women at increased breast cancer risk received a placebo, 5 or 50 mg of resveratrol twice daily for 12 weeks. Results were that there was indeed decrease in methylation of the tumor suppressor gene with increasing levels of resveratrol (P = .047).

In another study²⁶ of 34 overweight, postmenopausal women (BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic sex steroid hormones were investigated, since high estrogen levels may contribute to breast cancer. The subjects received 1 g of resveratrol daily for 12 weeks. The results were that resveratrol supplementation led to an average of 73 percent increase in urinary 2-hydroxyestrone (the “good estrogen”) levels leading to a favorable change in estrogen ratios that are less conducive to the development of breast cancer. This research demonstrated that among overweight and obese postmenopausal women, a daily 1 g dose of resveratrol has favorable effects on estrogen metabolism.

Muscle Health
In a 12-week study,²⁷ older men and women (aged 65.80 years) exercised and took either a placebo or 500 mg/day of resveratrol to determine if resveratrol would have additive effects to those of exercise. Results showed that exercise added to resveratrol treatment increased the number of mitochondria, and improved muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects treated with resveratrol had an increase in muscular torque and power after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with resveratrol significantly improved muscle fiber. Together, these data suggest that resveratrol combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Cognitive Health
Research suggests that resveratrol may have cognitive health benefits in people with and without dementia. For example, the ongoing dysfunction of small blood vessels in patients with type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to various brain regions, thereby increasing risks of dementia. To determine if resveratrol could benefit cerebral circulation, a study²⁸ was conducted in which 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Results were that 75–300 mg of resveratrol enhanced vasodilator responsiveness in cerebral vessels.

In another study,²⁹ 80 post-menopausal women aged 45–85 years received resveratrol or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

To test³⁰ whether supplementation of resveratrol (200 mg/ day for 26 weeks) would enhance memory performance in older adults, 23 healthy overweight older individuals were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50–75 years). Results showed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038), significant increases in hippocampal functional connectivity, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p < 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism in older adults, providing a basis for helping to maintain brain health during aging.

To determine the effects of oral resveratrol on localized cerebral blood flow, a study³¹ was conducted with which 22 healthy human adults received placebo and two doses (250 and 500 mg) of resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks. Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, and enhanced oxygen extraction. These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Finally, a clinical study³² was conducted to determine if up to 1 g of resveratrol twice daily could benefit Alzheimer’s disease (AD) patients. The results demonstrated that resveratrol decreased CSF MMP9 (a biomarker for confirmed AD), modulates neuro-inflammation, and induces adaptive immunity— suggesting that resveratrol may be a viable target for treatment or prevention of neurodegenerative disorders.

Weight Loss
One of the reasons that resveratrol has received widespread interest is because of its ability to mimic effects of calorie restriction. To gain more insight into this effect on adipose tissue, a study³³ was conducted in which healthy obese subjects were supplemented with 150 mg/day of resveratrol or placebo for 30 days. Results showed that resveratrol significantly decreased the size of adipocytes (fat cells), with a shift toward reducing the proportion of large and very-large adipocytes and an increase in small adipocytes. Furthermore, lysosomal/phagosomal pathway and transcription factor EB were up-regulated reflecting an alternative pathway of lipid breakdown by autophagy.

Similarly,³⁴ T2DM patients received 3 g resveratrol or placebo daily for 12 weeks. Results were that there was a significant increase in both SIRT1 expression and resting metabolic rate compared with the placebo group. In patients with T2DM, treatment with resveratrol helped regulate energy expenditure, suggesting that resveratrol may have beneficial exercise-mimetic effects.

Again,³⁵ healthy, obese subjects were treated with placebo and 150 mg/day resveratrol for 30 days. The results were that resveratrol increased SIRT1 and improved the muscle’s use of fatty acids as an energy fuel, demonstrating that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Given these results, one might think that resveratrol may aid in weight loss—and indeed this has been shown to be the case in clinical research.

Orlistat is an over-the-counter drug (also known as Alli®) designed to treat obesity by reducing the absorption of fats from the human diet. A study³⁶ was conducted to evaluate the efficacy of combining orlistat with resveratrol in 84 obese subjects over a 6-month period. The subjects consumed a diet with 500 fewer calories than their usual diet for two weeks, and were randomly assigned to four groups, placebo, resveratrol, orlistat, or the O-R combination, and they consumed the energy-reduced diet for 6-months. Results were significant weight loss of 15 lbs in the O-R group compared with 7.7 lbs in the placebo group. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination, indicating that it was the most effective weight loss treatment.

In another study,³⁷ 24 patients with metabolic syndrome received resveratrol (500 mg) three times per day before meals for 90 days. Resveratrol administration resulted in significant differences in total weight (P=0.007), body mass index (BMI) (P=0.006), fat mass (P=0.001), and waist circumference (P=0.004). In conclusion, administration of resveratrol significantly decreased weight, BMI, and fat mass.

Blood Sugar/Insulin Resistance
A study³⁸ was conducted using 480 mg/day of resveratrol or placebo for four weeks on 43 patients with diabetes who also had chronic periodontitis (i.e. gum disease). Results were that serum levels of fasting insulin and insulin resistance were significantly lower in the resveratrol group compared with control group. With regard to periodontal disease, there was also a significant difference in the gum pocket depth between intervention and control groups with resveratrol. The researchers recommended that resveratrol supplementation might be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.

Another human clinical trial³⁹ was conducted in 32 over-weight, older adults (average age: 73 years). Participants received placebo, 300 mg/day of resveratrol, or 1000 mg/day of resveratrol for 90 days. Results were that, compared to placebo, glucose levels were significantly lower at after treatment among participants receiving either dose of resveratrol (P<0.05), and were well tolerated.

In this study,⁴⁰ 62 patients with T2DM received either an oral hypoglycemic medication, or an oral hypoglycemic medication along with 250 mg/day of resveratrol. Results were that supplementation with resveratrol for three months significantly improved the mean hemoglobin A1c (P<0.05), a measure of long-term glucose control, systolic blood pressure (P<0.05), total cholesterol (P<0.05), and total protein (P<0.05) in T2DM. The researchers concluded that oral supplementation with resveratrol was effective in improving glycemic control and may be a potential adjuvant for the treatment and management of diabetes.

In a pilot study,⁴¹ subjects with impaired glucose tolerance (aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for four weeks. After four weeks of resveratrol supplementation, results showed that post-meal (P=0.003) and 3-hour glucose levels (P=0.001) declined. Researchers concluded that, at doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and post-meal plasma glucose in subjects with impaired glucose tolerance. Likewise, in a 4-week study,⁴² T2DM patients received 10 mg/day resveratrol or a placebo. Results showed that, after the fourth week, resveratrol significantly improved insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin-signaling pathway.

Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver of people who drink little or no alcohol. Unfortunately, NAFLD is common—with easily one-third of all American adults being affected⁴³—and often causes no signs and symptoms, and sometimes no complications. In more serious cases, however, the fat that accumulates in NAFLD can cause liver inflammation and scarring.⁴⁴ In addition, NAFLD is usually associated with insulin resistance, central obesity, reduced glucose tolerance, T2DM and high triglyceride levels.

In a clinical study,⁴⁵ 50 NAFLD patients received either a 500 mg/day of resveratrol or a placebo for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. Results were that resveratrol supplementation reduced alanine aminotransferase (a marker for NAFLD) and hepatic steatosis (fatty liver) significantly more than placebo (P<0E05).

In another study,⁴⁶ 60 NAFLD patients received two 150 mg resveratrol capsules twice daily for three months. Results were that, compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol (P.0.001) alanine aminotransferase, total cholesterol (P=0.002), and insulin resistance (P=0.016). The researchers concluded that resveratrol supplementation might benefit patients with NAFLD.

Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol, there are additional benefits for this nutraceutical as well. Two such benefits are related to bone health, and for those who are smokers.

In a clinical study,⁴⁷ 66 middle-aged, obese subjects with metabolic syndrome (average age: 49.3 } 6.3 years) received oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo daily for 16 weeks to assess changes in the bone turnover marker bone alkaline phosphatase (BAP), and bone mineral density (BMD). Results were that BAP increased dose dependently with resveratrol (P<0.001), compared with placebo. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol (P=0.036), with a significant increase of 2.6 percent in the 1,000 mg resveratrol group compared with placebo (P=0.043). In addition, changes in BAP and bone mineral density were positively correlated (P=0.027).

Smokers typically experience a state of low-grade systemic inflammation and oxidant-antioxidant imbalance. To determine whether resveratrol has beneficial effects on markers of inflammation and oxidative stress, a study⁴⁸ was conducted with 50 healthy adult smokers who alternatively were given 500 mg/ day of resveratrol and placebo. Results were that resveratrol significantly reduced the inflammatory marker C-reactive protein (CRP), triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. The researchers concluded that, because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation might beneficially affect the increased cardiovascular risk of healthy smokers.

Improving The Bioavailability And Efficacy Of Resveratrol

Now that we’ve reviewed some of the many benefits associated with resveratrol supplementation, let’s briefly consider ways to improve the bioavailability and efficacy of this valuable nutraceutical. First, take resveratrol on an empty stomach. The reason for this recommendation is a study showing that the absorption rate of resveratrol following an oral 400 mg single dose was significantly delayed by the presence of food.⁴⁹

Second, resveratrol may work better when taken together with pterostilbene (a related antioxidant) and quercetin (a flavonoid). In this study,⁵⁰ the antioxidant activities of resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human blood cells in-vitro. When used together, the combination protected the blood cells against destruction and against depletion of the important antioxidant, glutathione. Also, the combination of resveratrol with quercetin or pterostilbene synergistically inhibited oxidative injury of membrane lipids. These protective effects may partially explain the health benefit of these bioactive micro-components when together in the diet.

Conclusion
The value of supplementation with resveratrol has moved beyond the “French paradox” and the activation of the SIRT 1 gene, associated with longevity. Human clinical research has demonstrated efficacy of resveratrol for inflammation, immune health/breast cancer prevention, muscle health, cognitive health, weight loss, blood sugar/insulin resistance, non-alcoholic fatty liver disease, and more.

Endnotes

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48. Vaz-da-Silva M, Loureiro AI, Falcao A, Nunes T, Rocha JF, Fernandes-Lopes C, Soares E, Wright L, Almeida L, Soares-da-Silva P. Effect of food on the pharmacokinetic profile of trans-resveratrol. Int J Clin Pharmacol Ther. 2008 Nov;46(11):564–70.
49. Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr. 2010 Mar;65(1):57–63

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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-twenty-five, 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 health-protective 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.

References

1. 1. 1. F. Hinman, Benign Prostatic Hypertrophy. New York: Springer-Verlag, 1983.
      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. Experts slam omega-3 link to prostate cancer as overblown ‘scaremongering.’ http://www.nutraingredients.com/content/view/print/796071
      4. Ibid.
      5. http://www.foodnavigator-usa.com/news/printNewsBis.asp?id=65537
      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. http://zonediet.com/blog/2013/07/
      8. A glass of red wine a day keeps prostate cancer away?
      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. 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. 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. 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. 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. TotalHealth Online: Going Wild With Bitter Melon for Blood Sugar Support
      15. Goodman A. High Marks for Nutritional Supplement in Patients with Localized Prostate Cancer. Value-Based Cancer Care. September 2013 Vol 4, No 7.
      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. 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. 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. 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. 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. 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.
      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 Multi-ethnic Cohort Study. Am J Epidemiol. 2007 Dec 1;166(11):1259–69.
      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. 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.

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