Preventitive Effects of lignan Extract from Flax Hulls On Experimentally Induced Benign Prostate Hyperplasia

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign hyperplasia (BPH).  This study investigated whether a lignan rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP) induced BPH rat model.  Male Wistar unilever rats were randomly divided into four groups of 12 rats each:  a negative control group fed with control diet and receiving daily LLE (LLE 0.5) or 1.0 percent LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil.  Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks.  The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5 week treatment period.  TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced, significantly this MBWG reduction in a dose to dependent manner.  The lignan rich extract significantly inhibited TP induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls.  This effect was dose dependent.  Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats.  It was concluded that the lignan rich flaxseed hull extract prevented the TP  induced BPH indicating it might be beneficial in the prevention of BPH. (Authors abstract)

Benign Prostatic Hyperplasia (also known as benign prostatic hypertrophy (BPH) is one of the most common health problems occurring in middle to aged elderly men, with an incidence of approximately 50 percent in those aged 60 or older, and more than 90 percent in men older than 85.  .  Sex hormones, such as the androgens testosterone and dihydrotestosterone (DHT), not only play an important role in the growth, maintenance, and function of the normal prostate gland but also in the pathogenesis of BPH.  The primary androgen responsible for the pathogenesis of BPH is DHT, which is formed upon the conversion of testosterone by the enzyme 5a reductase leading to an increased level of DHT in the prostate.  Due to the imbalance between testosterone and DHT in the circulation and/or prostate tissue linked to the enzyme 5a reductase, which excessively catalyzes DHT production from testosterone, DHT stimulates prostate tissue proliferation via binding with adrenergic receptors.  Research into natural alternatives for pharmacological treatments, concerning the prevention and treatment of symptoms linked to BPH, has focused mainly on standardized plant extracts such Serenoa repens extract, polyphenolic extracts of cocoa, and flaxseed lignan extract.

The lignans, a class of phytoestrogens, are biologically active compounds with weak estrogenic or anti to estrogenic, antioxidant, and antitumor properties, mediated through inhibition of growth signal factors and modulation of enzymes involved in the hormone metabolism that can influence prostate metabolism.  Diets high in lignans may provide health benefits by decreasing the risk of hormone to dependent diseases and conditions associated with increased inflammation and oxidative damage.  Furthermore, it has been reported that END and ENL can inhibit 5a reductase which might suggest the possible benefits of flaxseed supplementation in people with BPH. The aim of this study was to investigate the preventive effects of a lignan rich extract from flaxseed hulls incorporated in diet, against testosterone to induced BPH in male Wistar to Unilever rats in order to investigate the beneficial effect of preventive treatments with LLE in the management of BPH. It was demonstrated that LLE provided to rats in the diet before the induction of BPH, significantly reduced the pathology in a dose to dependent manner inhibiting prostate growth and normalizing food consumption.

Treatments with LLE incorporated in the diet at the highest tested dose of 1.0 percent limited the effects of TP on rat BW, leading to a significantly increased MBWG during the period of induction of BPH in comparison with induced control rats fed with control diet (positive control) or diet containing 0.5 percent of LLE (LLE 0.5) and thereby normalizing the MBWG. The effect of LLE was significant on prostate weight and prostate weight ratio:  both average prostate weights and prostate weight ratios were significantly lower in rat fed with the diet enriched with LLE at both doses of 0.5 percent and 1.0 percent in comparison with positive control rats fed with the control diet.  In addition, the effect was more pronounced with the highest tested dose of 1.0 percent of LLE.  The consumption of LLE at both doses also led to a significant elevation of serum and urinary levels of ENL in a dose to dependent manner.  These results show that the flax lignan SDG in LLE is converted by the rats to the enterolignan ENL. 

In the present study, the efficacy of LLE in preventing BPH was dose to dependent.  Serum ENL concentrations determined at the end of the 5 week treatment period were 5 to 10 times higher in animals fed the LLE enriched diets than rats fed with the control diet.  Urinary ENL concentrations measured on the same rats at the end of the 5 week treatment period were 2 to 10 times more important than the two control groups fed with the control diet.  Flaxseed lignans delay the development of prostate growth and one likely mechanism is the inhibition of 5a reductase by ENL.  Further studies aimed at determining mechanisms of action of LLE are now necessary to further explore the preventive efficacy of lignans and their metabolites.