Almost all aspects of urology are affected positively and negatively by certain lifestyle changes and dietary supplements. Some of these interventions have potential profound impacts independently or in combination with conventional therapy, others have no impact, and some could negatively impact treatment and overall health. The heart-healthiest recommendations have consistently served as the safest and most potentially effective options in urology from benign prostatic hyperplasia, chronic nonbacterial prostatitis, interstitial cystitis, multiple urologic cancers, male infertility, male and female sexual dysfunction, kidney stones, and Peyronie disease.
Almost all aspects of urology are affected by lifestyle changes and dietary supplements. Yet, putting a quick summary together of these interventions is a daunting task because some of these interventions have potential profound impacts independently or in combination with conventional therapy, others have no impact, and some could negatively affect treatment and overall health. Over the last decade, few specialties have arguably invested more energy and effort in determining whether or not certain dietary supplements affect a variety of medical conditions than urology. Thus, a quick review of potentially efficacious and nonefficacious lifestyle and supplemental interventions seems necessary.
Benign prostatic hyperplasia
Benign prostatic hyperplasia (BPH) or lower urinary tract symptoms have a long history of being positively affected by heart-healthy lifestyle changes. Thus, reminding patients that almost anything heart healthy is prostate healthy is a simplistic and important mantra. Conversely, heart-unhealthy changes increase the risk of exacerbation of BPH, such as lack of exercise, obesity, excess alcohol intake, poor mental health, high cholesterol level, heart disease, hypertension, diabetes, tobacco use, and so forth, which all seem to have a potential profound impact via multiple mechanisms, including increased sympathetic tone, cholesterol, oxidative stress, and so forth.
β-Sitosterol and Other Cholesterol Reducers
Phytosterols are found in a variety of plants and plant oils. Phytosterols are similar in structure to cholesterol except for a minor structural difference. Phytosterols are not synthesized in humans and are not well absorbed, are excreted more rapidly from the liver than cholesterol, and are not found in high concentrations in human tissues. The main phytosterols found in the diet are sitosterol, stigmasterol, and campesterol. β-Sitosterol is the phytosterol found in largest quantity in the diet. Phytosterols block the uptake of exogenous cholesterol from dietary and bile sources in the intestinal tract. Low-density lipoprotein (LDL) cholesterol is reduced by phytosterols, and high-density lipoprotein (HDL) and triglycerides are not affected. The blockage of cholesterol absorption may produce a relative cholesterol pool reduction, which is followed by upregulation of cholesterol synthesis and LDL receptors, which can increase LDL removal. This process is similar to how some healthy dietary fats found in many healthy foods, such as almonds or pistachios, may also reduce LDL levels and improve some specific urologic outcomes.
More than 40 clinical trials of phytosterols have been conducted that have ranged from 1 to 12 months. Plant sterols added to foods such as yogurt, margarine, orange juice, mayonnaise, milk, and olive oil have been shown to reduce LDL level by approximately 10% to 15% (mean of 10%–11%) when approximately 2000 mg/d is ingested. About 1600 to 3000 mg of plant sterol supplemental or tablet consumption can also reduce LDL levels by approximately 4% to 15%. Plant sterols may also reduce the absorption of some fat-soluble vitamins; so, there has been some debate as to whether multivitamins should be consumed with the use of these products.
The primary mode of action of these sterols via cholesterol uptake reduction and a minor antiinflammatory mechanism suggests, in my opinion, that they are weaker mimics of the drug ezetimibe (Zetia), which can reduce LDL levels by approximately 20% with a 10-mg dose. Recently, laboratory research has demonstrated the ability of ezetimibe to favorably affect prostate tissue and reduce BPH. Ezetimibe is commonly added to statin therapy or other lipid-lowering agents to achieve synergistic impacts and, more favorably, reduce LDL level. Therefore, it should not be surprising that β-sitosterol by itself or with other cholesterol-lowering medications could favorably affect BPH. For example, despite some data that suggest no impact of statins on established BPH over a short period, other new epidemiologic and past laboratory studies suggest potentially favorable impacts on BPH prevention and progression with cholesterol-lowering prescribed medications.
Two meta-analyses, performed by similar investigators in 1999 and 2000, suggested that β-sitosterol could provide some benefit for men with BPH. In some of these studies, β-sitosterol is an extract that contains a variety of phytosterols or plant cholesterols that are usually derived from the South African star grass ( Hypoxis rooperi ). Researchers reported an impressive mean difference compared with placebo; the International Prostate Symptom Score was −4.9 points, peak urinary flow rate was 3.91 mL/s, and residual volume was −28.62 mL. β-Sitosterol did not affect prostate size, which is of interest because there is some preliminary evidence that it may mildly inhibit 5α-reductase. The withdrawal rates were similar to those of placebo (approximately 8%). Most common side effects with β-sitosterol were gastrointestinal side effects in 1.6% and erectile dysfunction in 0.5%. These analyses were conducted from 4 trials that involved 519 men. The question is to why not try β-sitosterol, a heart health ingredient, with or without medications for BPH. The dosage range in these studies has been from 0.30 mg of β-sitosterol-β- d -glucoside to approximately 200 mg/d. However, the dosage recommended in cholesterol treatment guidelines is 2000 to 3000 mg a day to reduce LDL by 6% to 15%, and, in fact, these National Cholesterol Education Panel recommendations state that “Plant stanol/sterol esters (2 g/day) are a therapeutic option to enhance LDL cholesterol lowering.” However, no recent studies of β-sitosterol have been published, but, if a patient is going to use a cost-effective product for cholesterol reduction, it is theoretically possible that a secondary benefit may be prevention or reduction in some aspect of BPH.
A 2002 meta-analysis of 18 Pygeum africanum clinical trials suggested a potential benefit with this supplement. These compounds are an extract of the African prune tree. The mean duration of clinical studies was 64 days, but men were more than 2 times as likely to report an improvement in overall symptoms; nocturia was reduced by 19%, residual volume was reduced by 24%, and peak urine flow was increased by 23%. The withdrawal rate was similar to placebo at 12%. Adverse effects were similar to those of placebo, and the most frequently reported adverse effects were gastrointestinal. Most studies used a standardized extract effective at approximately 100 to 200 mg/d. One of the main components of Pygeum africanum and saw palmetto are phytosterols that include β-sitosterol. However, the problem with Pygeum is demand compared with precious supply, in that the bark is derived from an endangered tree. This is not the case with saw palmetto, which seems to be in abundance and has arguably a diverse number of heart-healthy compounds beyond β-sitosterol, including the primary monounsaturated fat found in olive oil (oleic acid) and a variety of other potentially healthy dietary fats that may have the ability to increase HDL levels and lower cardiovascular events.
Chronic nonbacterial prostatitis and interstitial cystitis
Dietary supplements in chronic nonbacterial prostatitis and interstitial cystitis are actually fairly well known and have a history of being heart healthy, and some even reduce blood pressure in prehypertensive patients. Less known is that there is a history of some heart-healthy lifestyle changes that have also displayed some preliminary profound effects.
A randomized double-blinded lifestyle clinical study from Florence, Italy, had impressive results because the participants were previously unresponsive to conventional treatments. Participants (average age of 36–38 years, body mass index [BMI, calculated as the weight in kilograms divided by height in meters squared] of 22, mean symptom duration of 5.5–6 months) had symptoms of pain in the pelvic region for 3 or more months continuously and scored a minimum of 15 points on the National Institutes of Health–Chronic Prostatitis Symptom Index (NIH-CPSI) with at least 6 or more points on the pain subscale. A total of 52 subjects were placed in the exercise group and 51 were assigned to the placebo/stretching group. The outcome measures were the NIH-CPSI, the Beck Depression Inventory, the State Anxiety Inventory-Y, and a pain visual analog scale (VAS). These evaluations were determined at baseline and 6 and 18 weeks. The exercise group engaged in vigorous walking 3 times per week for 40 minutes of each session to achieve 70% to 80% of the predicted maximum heart rate for their age. The placebo/stretching group did a series of stretching exercises but had to maintain their heart rate below 110 beats per minute for the entire session. Approximately 25% of the participants dropped out of the study by 18 weeks. However, significant differences between the 2 groups favored the exercise group for total NIH-CPSI ( P = .006), pain ( P = .0009), quality-of-life subscales ( P = .02), and VAS ( P = .003). No difference was found for other parameters. Responders were considered those who experienced a decrease of 6 or more points in total NIH-CPSI (58% exercise vs 43% placebo), 25% to 49% (39% vs 35%), and a decrease of 50% (19% vs 5%) or more from baseline in total NIH-CPSI. A placebo response of 25% of this magnitude is expected from other trials. Pain is the symptom that is the most influential variable and the quality-of-life predictor and should be one of the main targets of any therapy. Exercise induces release of endogenous opioids and reduces sympathetic activity to the prostate.
Chronic nonbacterial prostatitis and interstitial cystitis
Dietary supplements in chronic nonbacterial prostatitis and interstitial cystitis are actually fairly well known and have a history of being heart healthy, and some even reduce blood pressure in prehypertensive patients. Less known is that there is a history of some heart-healthy lifestyle changes that have also displayed some preliminary profound effects.
A randomized double-blinded lifestyle clinical study from Florence, Italy, had impressive results because the participants were previously unresponsive to conventional treatments. Participants (average age of 36–38 years, body mass index [BMI, calculated as the weight in kilograms divided by height in meters squared] of 22, mean symptom duration of 5.5–6 months) had symptoms of pain in the pelvic region for 3 or more months continuously and scored a minimum of 15 points on the National Institutes of Health–Chronic Prostatitis Symptom Index (NIH-CPSI) with at least 6 or more points on the pain subscale. A total of 52 subjects were placed in the exercise group and 51 were assigned to the placebo/stretching group. The outcome measures were the NIH-CPSI, the Beck Depression Inventory, the State Anxiety Inventory-Y, and a pain visual analog scale (VAS). These evaluations were determined at baseline and 6 and 18 weeks. The exercise group engaged in vigorous walking 3 times per week for 40 minutes of each session to achieve 70% to 80% of the predicted maximum heart rate for their age. The placebo/stretching group did a series of stretching exercises but had to maintain their heart rate below 110 beats per minute for the entire session. Approximately 25% of the participants dropped out of the study by 18 weeks. However, significant differences between the 2 groups favored the exercise group for total NIH-CPSI ( P = .006), pain ( P = .0009), quality-of-life subscales ( P = .02), and VAS ( P = .003). No difference was found for other parameters. Responders were considered those who experienced a decrease of 6 or more points in total NIH-CPSI (58% exercise vs 43% placebo), 25% to 49% (39% vs 35%), and a decrease of 50% (19% vs 5%) or more from baseline in total NIH-CPSI. A placebo response of 25% of this magnitude is expected from other trials. Pain is the symptom that is the most influential variable and the quality-of-life predictor and should be one of the main targets of any therapy. Exercise induces release of endogenous opioids and reduces sympathetic activity to the prostate.
Kidney/bladder/prostate cancers
One of the strongest correlations for any cancer risk or progression and smoking is not just lung cancer but bladder cancer. In addition, smoking after bladder or prostate cancer treatment may also increase the risk of cancer recurrence and heart disease. Obesity is linked to multiple cancers, but kidney cancer (renal cell) has arguably the strongest correlation of almost any cancer type in terms of a higher risk with a greater BMI or waist circumference. Hypertension, lack of exercise, smoking, and even dyslipidemia may also be associated with increased risks of kidney cancer. Almost every heart-healthy behavior that one can imagine is associated with a potential lower risk of prostate cancer. Few medical specialties seem to have such a close correlation with cardiovascular health and risk compared with urology.
In terms of dietary supplementation, there is evidence to suggest that high doses of or megadosing on most dietary supplements or antioxidants does not seem to provide benefit and may even encourage tumor growth in some cases. This evidence is similar to the evidence that has already existed in terms of cardiovascular risk increases with larger intakes of dietary supplements.
In a small and randomized study from the 1990s, there was a suggestion that megadoses of a supplement as opposed to a recommended daily allowance (RDA) supplement may reduce the risk of non–muscle-invasive bladder cancer recurrence after BCG treatment. However, a larger follow-up study was needed to confirm these preliminary findings, which recently occurred. Patients who were BCG naive with carcinoma in situ, Ta bladder cancer, or T1 bladder cancer were randomized to receive intravesical BCG or BCG plus interferon alfa-2b and then further randomized to receive an RDA (minimal intake) or megadose supplement. Each RDA tablet of vitamins contained 25% of the recommended daily dose, and patients took 2 tablets twice daily of either the RDA or the megadose supplement. Each megadose tablet contained 9000 IU of vitamin A, 25 mg of vitamin B6, 500 mg of vitamin C, 400 IU of vitamin D3, 400 μg of folate, 100 IU of vitamin E, and 7.6 mg of zinc. Induction BCG was given weekly for 6 weeks and then at 4, 7, 13, 19, 25, and 37 months. The primary end point was biopsy-confirmed recurrence or cytology that was positive. A total of 670 patients were randomized, and, at a 24-month median follow-up, there were no significant differences between the RDA and megadose supplements groups. The following recurrence-free survival numbers were BCG + RDA, 63%; BCG + megadose supplement, 59%; BCG + interferon + RDA, 55%; and BCG + interferon + megadose supplement, 61%. Megadose supplements and/or interferon alfa-2b added to BCG did not affect time to recurrence in patients with non–muscle-invasive bladder cancer. Also, there was a slight nonsignificant increased risk of recurrence with BCG and the megadose supplement.
When the first study was published in the 1990s in the Journal of Urology , it was visionary, and megadose vitamins probably did reduce the risk of recurrence in my opinion. Why? Researchers were arguably dealing with a population of individuals that had deficiencies in a variety of vitamins and minerals. Fast-forward almost 2 decades later and patients are not deficient but seem to be oversupplemented with antioxidants from foods, beverages, and supplements. This oversupplementation makes it difficult to truly conduct a large clinical trial of a truly deficient healthy population over a long period, despite some investigators calling for the need for such studies because when these clinical trials are designed, deficiencies are more prevalent, but, by the time the trial commences, the deficiencies may no longer exist. In addition, in the more recent bladder cancer trial, the megadose supplement itself had added folic acid and vitamin D to it compared with the original formulation used in the preliminary successful study. Why was the formula altered from what was potentially successful in the preliminary study because of some minimal laboratory and population data? Would this formula be allowed in definitive phase 3 pharmaceutical studies in which the phase 1 or 2 had a successful outcome and safety with a specific dose and formulation, which was altered in the phase 3 trial? Arguably these nutrients, especially folic acid, also have data to suggest that they could also increase recurrence of certain cancers or other abnormalities when given at these higher doses. Lower doses of these supplements may be providing the benefits needed without adding the significant increased risks or overall concerns for most individuals. Over the past 20 years, multiple randomized trials and some observational studies suggest that a potentially heart- and digestive-healthy probiotic found in some types of yogurt and available as potential dietary supplement may reduce the risk of bladder cancer or recurrence after conventional treatment.
Infertility and sexual dysfunction
Heart-unhealthy behaviors also negatively affect male fertility. Obesity, high cholesterol and blood pressure, lack of exercise, improper diet, stress, depression, and multiple other cardiovascular risk factors that increase oxidative stress all have some minor or major impact on fertility and are arguably the most holistic approach to changing patients lives and improving overall outcomes.
Authoritative medical reviews have suggested that antioxidant supplement treatment could be considered a primary treatment of some male fertility issues. In addition, a recent Cochrane review is one of the most extensive published data on male fertility and dietary supplements because it reviewed 34 clinical trials with 2876 couples. The overall findings concluded that antioxidant supplementation in men seems to have a positive role in improving the outcomes of live birth and pregnancy rates in couples participating in assisted reproduction techniques. The P values for live births and pregnancy rates were .0008 and .00001, respectively. Critics of this analysis on live births also arguably point toward the small number of such events (n = 20) that occurred from a total of 214 couples in only 3 studies that was used in this part of the analysis or the pregnancy rates that actually were derived from 96 pregnancies in 15 trials that included 964 couples. Yet, it is still relevant that this is a viable minimal or moderate option for some men, given the low cost of most antioxidants used in these studies. In addition, adverse events were similar to those of a placebo, with no serious adverse events reported in any trial.
Which specific dietary supplements and at what dosage and frequency should be recommended for male fertility issues? This extensive Cochrane review could not identify one superior individual antioxidant or combination product from these trials, so clinicians and patients are left with questions. In my opinion, the supplements that have a past overall safety record that may be heart healthy should be the only ones recommended for fertility from this past review, especially if there is equivalent efficacy among all the trials with positive results, in other words, coenzyme Q10 at 200 to 300 mg/day, l -carnitine at 2000 to 3000 mg/d, ω-3 fatty acids (fish oil), and vitamin C but not high-dose supplements that have a potential heart-unhealthy or overall male-unhealthy profile such as folic acid, selenium, and vitamin E, or even megadoses of zinc.
One of the more overt examples of heart-healthy lifestyle changes positively affecting urologic health has to be in male and female sexual dysfunction. These changes can also improve the efficacy of prescription erectile dysfunction medications. This category is one of the easiest for the reader to locate healthy lifestyle and supplement recommendations in the medical literature, which shows how far this area of urology has progressed.
Summary
Heart healthy seems tantamount to overall urologic health. This concept also potentially seems to be the case for kidney stones or choosing a supplement that could be used with conventional treatment of Peyronie disease. It seems that large and diverse (the American Cancer Society, the American Heart Association, and the American Diabetes Association) health care preventive organizations are beginning to apply this same concept because neither the truly life-changing lifestyle recommendations nor the dietary supplements for patients are mutually exclusive in my opinion. These lifestyle changes and dietary supplements affect a variety of potential clinical end points and have the highest overall probability of affecting all-cause mortality. This effect is critical in my opinion because again the forest has to take precedence over the tree to improve the overall state of urologic health. The less a clinician wants to focus on these issues, the less I also believe that patients will respond to them, and, even worse, the more likely in my opinion, patients will begin to listen to less-credible sources for guidance. This latter choice is simply not acceptable; however, this abnormal situation has become so common today in other nonurologic areas that it is almost considered normal for some patients to take lifestyle, supplement, and general preventive advices from the person at the counter of the local health food store over their practitioner. Perhaps this article is a simple small step in the appropriate direction. Heart health = urologic health should be the unified mantra for urologic practitioners because it is easy to construe for patients, is simple and fast for the clinician to recommend, and arguably has the best chance of immediately improving the lives of patients.
Related posts:
Quercetin for Chronic Prostatitis/Chronic Pelvic Pain Syndrome
The Complex Interplay Between Cholesterol and Prostate Malignancy
Pollen Extract for Chronic Prostatitis—Chronic Pelvic Pain Syndrome
Molecular Markers that Can Be Utilized in Diet and Dietary Supplement Research
Statin Clinical Trial (REALITY) for Prostate Cancer: an Over 15-Year Wait is Finally Over Thanks to a Dietary Supplement
Prostate Imaging Modalities that Can Be Used for Complementary and Alternative Medicine Clinical Studies
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