Benign Prostatic Hyperplasia (BPH)

Whom does BPH affect?

Benign Prostatic Hyperplasia (BPH) is a common male urological disorder.  Prevalence increases with age, with sixty percent of males affected by age ninety years (Lim, 2017).

Geographically, BPH occurs globally, but social stigma relating to symptoms of BPH and the association with ageing, may also contribute to under-reporting on a global scale (Nehra & Kulaksizoglu, 2002).

Epidemiological research concludes the risk of BPH significantly correlates with the number of close family members affected, suggesting a genetic component (Pearson et al. 2003).

Increasing body mass index (BMI) positively correlates with increasing incidences of BPH (Parsons et al., 2013).

What is the pathophysiology of BPH?

BPH is characterised by accelerated mitosis (cell division) of prostate epithelial and stromal cells, resulting in an enlarged prostate gland (McLaren et al., 2011).  This condition is inextricably linked with advancing age, possibly due to natural degeneration in Insulin-like Growth Factor (IGF) signalling pathways, altering tissue growth (Briganti et al., 2009).

Androgen (a type of hormone) metabolism may be a causative factor, and whilst testosterone levels decline with age, aromatase activity increases – increasing oestrogen in males (Araujo & Wittert, 2011).  Elevated oestrogen causes androgen receptors in prostate tissue to become hyper-receptive, which is associated with increased prostate growth (Smith et al., 2004).

Increased Dihydro-Testosterone (DHT) is a risk factor for BPH (Goldenberg et al., 2009).  Testosterone is converted to DHT by the enzyme 5-alpha-reductase, and in this form is a far more potent stimulator of androgen receptors (Wright et al., 1996; Eleazu et al., 2017).

Whilst androgen metabolism is widely accepted as a component of BPH, standard treatment to manipulate these hormones is not always effective, suggesting the aetiology must be multifactorial (Nicholson & Ricke, 2011).

Chronic low-grade inflammation is a prominent feature of BPH (Schauer & Rowley, 2011).  Inflammatory signalling molecules called interleukins may stimulate growth processes normally associated with early development, rather than the adult prostate (McLaren et al., 2011). 

As BPH progresses, the production of Prostate Specific Antigen (PSA) increases, which is detectable in blood (Esteban et al., 2016).

Due to the anatomical location of the prostate, the enlarged gland may encroach on the urethra, inducing lower urinary tract symptoms (LUTS).

Possible signs of an enlarged prostate (not an exhaustive list):

• Dysuria – Difficulty initiating urination / straining to urinate, a weak flow of urine, or intermittent urination with a ‘stop-start’ nature.
• Polyuria – Urinary urgency / frequency.
• Nocturia – Getting up in the night to pass urine.

 Reference: National Health Service, 2017 

IMPORTANT:  If you are experiencing any of the symptoms described above, or are generally concerned something is not quite right when you pass urine, speak to your GP without delay.  None of the information below is intended to replace the advice of your healthcare professional.

Conventional investigations of LUTS (carried out by a medical professional):

• PSA (Prostate Specific Antigen) – a blood test.
• Digital rectal examination – Part of the posterior section of the prostate gland can be manually felt via the rectum.  The medical professional may be able to feel whether the prostate gland is enlarged.
• Ultrasound – Ultrasound of the abdomen in the bladder region indicates the post-void residual to identify those at risk of urinary retention.
• MRI of the prostate – This may be done to determine the extent and classification of BPH.
• Uroflowmetry – Urinating into a specially designed machine provides data on the volume and speed of urinary flow during one void.

References: McVary, 2003; Guneyli et al., 2016; British Association of Urinary Surgeons, 2017; National Health Service, 2018; Prostate Cancer UK, 2019

Conventional treatment:

• Watchful waiting - Watchful waiting is the least invasive approach, involving monitoring of symptoms, PSA and prostate volume.  Active treatment is avoided until progression thresholds are reached (Wiygul & Babayan, 2009).
• Drug therapy –

Alpha-blockers (eg, Tamsulosin, Doxazosin, Alfuzasin, Silodosin and Terazosin).  Adrenergic receptors include alpha and beta receptors.  When smooth muscle alpha receptors are stimulated by adrenaline or noradrenaline, the smooth muscle constricts.  Alpha-blocker drugs prevent this process from happening, resulting in relaxation of smooth muscle within the prostate, which reduces LUTS (Koshimizu et al., 2003; Lepor, 2007).

5-alpha-reductase inhibitors (eg, Finasteride and Dutasteride).  Drugs that inhibit the enzyme 5-alpha-reductase, reducing conversion of testosterone to DHT (Goldenberg et al., 2009).

Anticholinergic / antimuscarinic drugs (eg, Solifenacin and Oxybutanin).  Triple mode of action; direct antispasmodic effect on bladder smooth muscle, acetylcholine antagonist of muscarinic receptors, and mild anaesthetic action locally within the bladder (Kennelly, 2010). 

• Surgical procedures for BPH - Holmium Laser Enucleation of Prostate (HoLEP), Transurethral Resection of the Prostate (TURP), embolisation of the prostatic arteries, “Millin’s procedure” open prostatectomy (Placer et al., 2015; The British Association of Urological Surgeons, 2017; Petrillo et al., 2018).

What are the naturopathic considerations of BPH?

Metabolic syndrome / inflammation

Metabolic syndrome encompasses; truncal obesity, hypertension, blood glucose derangement, insulin resistance, and dyslipidaemia (Laakso et al., 2017).  All have individually been associated with BPH (Michel et al., 2004; Nandeesha et al., 2006; Jung et al., 2016;).  Systemic inflammation is a feature of all of these conditions, supporting the likelihood of BPH involving an inflammatory mediator (McLaren et al., 2011; Schauer & Rowley, 2011).  Additionally, increased incidences of these conditions correlate with increasing age, as is the case in BPH (Shanmugasundaram et al., 2010; St-Onge & Gallagher, 2010; Kirkman et al., 2012; Evans & Goldfine, 2013; Buford, 2016).

Truncal obesity increases metabolically active visceral adipose tissue (VAT) (Gomez-Hernandez et al., 2016).  Specifically, the enzyme aromatase is upregulated, causing greater conversion of androgens to oestradiol (Zahid et al., 2016; Hetemaki et al., 2017).  Please refer to the beginning of this post for more on the relationship between oestrogen and BPH.

Leptin secretion increases with excess VAT, potentially causing leptin resistance.  This alters inflammatory cytokine production which influences insulin signalling pathways, possibly contributing to insulin resistance (Wang et al., 2001; Barnes et al., 2015; Osegbe et al., 2016). 

Hyperinsulinemia increases production of IGF, and both insulin and IGF levels are raised in BPH (Gallagher & LeRoith, 2010; Sreenivasulu et al., 2017).  IGF is associated with upregulated 5-alpha-reductase activity, therefore upregulated DHT (Horton et al., 1993).

Increased VAT is also associated with hyperuricaemia, which may stimulate the RAGE pathway, increasing inflammation (Duan et al., 2015; Zhang et al., 2016; Cai et al., 2017).

The inflammation theory is supported by evidence that anti-inflammatory pharmaceuticals reduce symptoms of BPH (St. Sauver et al., 2006).

Tip: There are many dietary and lifestyle factors that are thought to promote inflammation in the body.  A nutritionist can offer support with addressing these, but swapping ultra-processed foods for minimally processed foods is a great place to start.

Digestive function

Hepatic steatosis (fatty liver) may contribute to the conditions that comprise metabolic syndrome (Nseir et al., 2011).  Uzun et al. (2013) were the first researchers to establish an association between liver health and BPH.

Constipation may inhibit elimination of oestrogen, which can then be reabsorbed, increasing overall oestrogen levels (Maruti et al., 2008).  Whilst no primary research on the relationship between constipation and prostate enlargement is available, constipation is associated with LUTS (Thurmon et al., 2013).

Tip: Optimise your diet and lifestyle to ensure regular bowel movements.

Xenoestrogens

The role of oestrogen in BPH, raises questions regarding the role of xenoestrogens.  Bisphenol-A is widely accepted as an endocrine disruptor, and is specifically linked to increased 5-alpha-reductase and aromatase activity (Castro et al., 2013; Wynder et al., 2015).

Tip:  Avoid storing and eating food from plastic containers, particularly heated containers such as when heating meals in the microwave.  Avoid clingfilm, plastic lunchboxes, plastic cooking utensils, to reduce potential exposure to xenoestrogens (Wynder et al., 2015).  Use glass, beeswax, ceramic, wood replacements in the kitchen, as BPA-free accredited products may still leach other endocrine disruptors into food (Bittner et al., 2014).

Pesticides 

Pesticides are considered endocrine disruptors, and BPH sufferers have higher serum levels of organochloride pesticides, compared to non-BPH participants (Kumar et al., 2014).  Opposing research states there is no association between pesticides and BPH, but the study design required participants to recall episodes of pesticide exposure over several decades (Fritschi et al., 2007).

Tip:  Consider buying organic where possible – prioritise buying organic for any fruits where the skin is eaten.

How can nutrition help men with BPH?

Fruit and vegetables

Phytonutrients are compounds within plants that have therapeutic properties, including antioxidant activity, that may benefit clients with BPH (Eleazu et al., 2017).

Lycopene, found in tomato, may induce apoptosis (cell death) of prostate cells, thereby restricting growth (Minutoli et al., 2014).  Bear in mind that the participants in this study were rats not human males, and the lycopene sample included only seven rats in total.  However, another study, this time conducted on human participants, also found lycopene to be beneficial (Schwarz et al., 2008).  This randomised controlled trial measured prostate size via both physical examination and ultrasound, and assessed LUTS via participant questionnaires – all of which supported the hypothesis that lycopene is an effective intervention.

It is noted that the therapeutic dose of lycopene in the Schwarz et al. (2008) study was 15mg/day – too much to ingest in the form of whole tomatoes.  Research is readily available on whole tomato consumption and prostate cancer, but unfortunately not BPH.

A study involving >32,000 men found those with a diet high in fruits and vegetables, specifically the phytonutrients; lutein, beta-carotene, and zeaxanthin, were found to be less likely to develop BPH (Rohrmann et al., 2007).  Furthermore, research suggests LUTS decrease in men with a high dietary intake of carotenoids, rather than supplemental intake (Maserejian et al., 2011).

Fibre

Research on dietary fibre and BPH specifically is not available.  One study with a sample size of just fifteen men with BPH, did find their fibre intake was low (Goluch-Koniuszy et al., 2013).  However, this convoluted study looked at numerous nutritional factors, and included various prostate pathologies.  Despite this, fibre is associated with reduced circulating oestrogen, achieved by reducing beta-glucuronidase (an enzyme) activity, and by physically binding to oestrogen – increasing excretion (Gaskins et al., 2009).  Fibre is also associated with VAT reduction and improved blood-glucose control (Chen et al., 2016; Bozetto et al., 2018).

Anti-inflammatory foods

Although no research on fish consumption and BPH specifically is available, there is a plethora of evidence in support of fish and inflammatory conditions generally (Maroon & Bost, 2006; Lankinen et al., 2009; Ramel et al., 2010).

Flaxseed contains alpha-linolenic acid content, an omega 3 fatty acid associated with anti-inflammatory properties.  However, it appears the positive effect of flaxseed on BPH is more likely due to the lignan content (Zhang et al., 2008).  This study found flaxseed lignans to be as effective as alpha blockers and 5-alpha-reductase inhibitors.  However, once again, the independent variable was an isolated extract from the flax seed, not whole flax seeds.

Simons et al. (2015) found a placebo to be just as effective as flaxseed in reducing LUTS.  However, animal studies – which presumably eliminates the placebo element – continue to demonstrate flaxseed may be beneficial (Bisson et al., 2014).

Ginger compounds have been found to reduce TGF?1 – an inflammatory cytokine associated with stromal cell proliferation in BPH (Eid et al., 2017).  It is noted the participants were rodents, with experimentally induced diabetes, so human trials with non-diabetic participants are required.

A review of the research to date in 2007 found overwhelming evidence that garlic is beneficial in BPH (Devrim & Durak, 2007).  This was attributed to anti-inflammatory and antioxidant properties.  However, a recent study expands on this, finding garlic also prevents prostatic growth by inhibiting anti-apoptotic proteins (Chung et al., 2016).

Whilst the research on curcumin, found naturally in turmeric, and BPH specifically is limited, it is generally accepted that the compound does have antioxidant and anti-inflammatory properties (Zhang et al., 2010; Olivera et al., 2012).

Caffeine

Caffeine is a bladder irritant which exacerbates lower urinary tract symptoms (Maserejian et al., 2013).

Should I take supplements for BPH?

It is strongly recommended you seek professional advice before commencing supplements due to potentially harmful supplement-medication-food-herb interactions.  All supplements should be discussed with, and discontinued on the advice of a healthcare professional.  Seek professional advice on all supplements during pregnancy, whilst taking prescribed medication, and pre/peri/post-surgical procedures.

Beta-sitosterol

There is comprehensive evidence, including double-blinded placebo-controlled trials, that beta-sitosterols reduce LUTS (Wilt et al., 1999; Berges et al., 2001).

Probiotics

It was recently discovered that the urinary system is not sterile, but has resident beneficial microflora.  Furthermore, orally ingested probiotics can migrate from the colon, cross the perineum, and enter the urinary tract to influence the microbial balance in women with UTIs (Akgul & Karakan, 2018).  Given the potential involvement of E.coli (Roper, 2017), could probiotic supplements have therapeutic benefits for BPH?  Unfortunately, no studies on this are available, but possibly it is unlikely given the anatomical distance between anus and urethra being so much greater in males than females.

Probiotics may also modulate beta-glucuronidase activity, therefore the amount of oestrogen reabsorbed via enterohepatic circulation (Kwa et al., 2016).

Zinc

Zinc is more concentrated in the prostate, than any other bodily soft tissue (Kolenko et al., 2013).  Research suggests prostate zinc is reduced in BPH, but studies demonstrating the efficacy of zinc supplementation are extremely minimal (Christudoss et al., 2011)

Selenium

Selenium is highly concentrated in the prostate, and BPH sufferers have a lower circulating level of selenium (Zachara et al., 2005; Eichholzer et al., 2012).  However, Kristal et al. (2008) found no association between selenium supplementation and BPH.

Saw Palmetto

Saw Palmetto may inhibit the action of 5-alpha-reductase, reducing conversion of testosterone to DHT (Hoffmann, 2003).

There is extensive research on the efficacy of Saw Palmetto, with the majority – including the noteworthy CAMUS trial - finding it no more effective than a placebo (Bent et al., 2006; Barry et al., 2011; MacDonald et al., 2012; Andriole et al., 2013).  However, the findings of a very current, credible, double-blinded RCT conflicted with the general consensus, and actually found Saw Palmetto to be more effective than placebo (Ye et al., 2019).  Efficacy was reported for improving LUTS, quality of life, and sexual function.

Nettle

A recent double-blind randomised controlled trial showed improvements in all reported LUTS (Hosseinabadi et al., 2014).  This study did not include a placebo group, but did include a control group who received an alpha-blocker.  This group experienced fewer benefits than the combined nettle and alpha-blocker group.

Any other tips for men diagnosed with BPH?

• Exercise may positively influence LUTS by reducing obesity, systemic inflammation, and sympathetic nervous system dominance (Platz et al., 1998; Abramson & Vaccarino, 2002; Vesely et al., 2003; St Sauver et al., 2006; Wolin et al., 2015).
• Increase vegetable/fruit intake to 10 varied portions daily (of approximately 80g each) (Aune et al., 2017): Whilst the above research on individual phytonutrients is not conclusive, there are indications that phytonutrients collectively may be beneficial.  Fruit and vegetables also contain fibre and beta-sitosterols, which the evidence above overall suggests do have therapeutic benefits for BPH.
• Aim for approximately 30g of fibre a day (British Nutrition Foundation, 2019).
• Replace heavily processed food with non-processed food, ensuring the balance at every meal of complex carbohydrates, protein from a variety of sources, and healthy fats.  A nutritionist can advise on getting this balance right and provide examples.
• Freshly ground flaxseeds for potentially beneficial lignan content (Zhang et al., 2008).  Crush flaxseeds immediately prior to use to reduce oxidation of the alpha-linolenic acid within (Kajila et al., 2015).
• Use ginger, garlic and turmeric liberally in cooking (Zhang et al., 2010; Olivera et al., 2012; Chung et al., 2016; Eid et al., 2017).

About Katherine

Katherine Corsan is a BANT-registered nutritionist and owner of Sheer Nutrition in Salisbury.  A former registered nurse, Katherine now provides personalised one-to-one nutrition advice to clients with painful, embarrassing or exhausting symptoms, and has a special interest in digestive conditions.  Katherine also presents on a variety of health topics to support corporate wellbeing.

Consultations available online and face-to-face in Salisbury.

T.  07542 663 840

E.  info@sheernutrition.co.uk

www.sheernutrition.co.uk

Follow me on Instagram: sheer_nutrition

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