Ferianec V, Fülöp M, Ježovičová M., et al. The oak-wood extract Robuvit® improves recovery and oxidative stress after hysterectomy: a randomized, double-blind, placebo-controlled pilot study. Nutrients. March 27, 2020;12(4). pii: E913. doi: 10.3390/nu12040913.
Indications for hysterectomy, one of the most common gynecological surgeries, include premenopausal menorrhagia, pelvic pain due to endometriosis, and uterine prolapse. Malignancy and postpartum hemorrhage account for 10% of hysterectomies. While hysterectomy generally improves psychological and overall wellbeing, quality of life during recovery may suffer from fatigue, headache, nausea, depression or anxiety, pain, and wound infection or bleeding. There is no validated aid to postoperative recovery. With few studies on postoperative symptom pathophysiology, some have reported associations with oxidative stress—since surgery induces free radical production and inflammation. Herbal remedies including oak (Quercus robur, Fagaceae) wood extracts have been shown to reduce oxidative stress and boost energy in health individuals. The wound healing process after surgery also includes cell proliferation and tissue remodeling. As such, matrix metalloproteinases (MMPs)-2 and -9 are thought important in wound healing. The purpose of this randomized, double-blind, placebo-controlled pilot study was to investigate the effects of eight weeks of oak-wood extract intake on postsurgical mental and physical wellbeing, oxidative stress, and MMP-2 and -9 levels and activities.
Robuvit® (Horphag Research; Geneva, Switzerland), a French oak wood extract (Quercus robur, Fagaceae) has ≥40% polyphenols such as ellagitannins, including characteristic roburins, ellagitannin dimers with five reported structures (roburin A, B, C, D, and E). Ellagitannin monomers include stereoisomers vescalagin and castalagin. Robuvit also has gallic and ellagic acids. Ellagitannins, not absorbed in the gastrointestinal tract, are metabolized by gut bacteria to form urolithins. Ellagitannins are known antioxidants, as is ellagic acid, the latter with reported anti-inflammatory, antithrombotic, and antiplatelet effects. In prior studies, Robuvit increased total antioxidant capacity (TAC) and antioxidant enzyme activity while lowering levels of advanced oxidation protein products (AOPPs) and lipoperoxides (LPx). Gene expression analysis suggests that enzymes in serum after Robuvit may boost ribosomal function. Urolithin A promotes mitochondrial regeneration, increasing energy levels.
This study included 70 women with benign indications for a hysterectomy. The study took place from February 2015-June 2018 at Comenius University in Bratislava, Slovakia. Before surgery, patients did not take any analgesics or other drugs related to symptoms. As a pilot study, sample size was not calculated, but consenting women who met criteria were randomized to receive 100 mg Robuvit or placebo three times daily, starting on the third postoperative day, with 35 in each group. Both agents were provided by Robuvit's producer. Patients followed a standard diet and did not use other antioxidants or polyphenols during the study. Four dropped out before the intervention, leaving 33 in each group. Five from the Robuvit group and 13 from placebo dropped out after surgery for non-medical reasons. At week 4, there were 28 in the Robuvit group and 20 in the placebo group; at week 8, there were 24 and 17, respectively.
Clinical examinations were carried out before the intervention began (week 0) and four and eight weeks after. At each point, fasting venous blood samples were taken and recovery was rated via the SF-36 health survey. Glucose, creatinine, uric acid, triacylglycerols, total cholesterol (TC), low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-C, total proteins (TP), high-sensitivity C-reactive protein [hsCRP], and LPx levels were measured from plasma. Trolox equivalent antioxidant capacity (TEAC) was determined. Gelatinolytic activities of MMPs were analyzed by zymography, with MMP-9 and -2 identified by molecular weight. MMP-9 levels were measured via Western blot analysis. Changes in MMP activity and levels were expressed as % from baseline, preset to 100%.
There were no significant differences between groups in mean age or body mass index. Robuvit was well-tolerated, and no adverse effects were reported. Mean week 0 SF-36 scores did not differ significantly but by week 4 had significantly improved in the Robuvit group in general health (P = 0.016), social functioning (P = 0.031), and mental health (P = 0.019). Robuvit treatment effect was significant (P = 0.028). Placebo had no significant treatment effect, with negative SF-36 scores for several parameters at week 4. At week 8, scores in both groups exceeded week 0 values, indicating complete recovery for all patients.
Basic biochemical parameters and hsCRP were within normal ranges at baseline. TC and LDL-C were slightly elevated. TP, up after eight weeks with Robuvit, remained within the normal range, indicating increased protein synthesis, a factor in wound recovery. In the placebo group, TP did not alter significantly over eight weeks. hsCRP did not change significantly in either group. AOPP, LPx, and TEAC levels and MMP-9 activity were significantly different between groups at week 4 (for MMP-9, P = 0.006), indicating that Robuvit reduced oxidative stress. At week 8, MMP-9 activity did not differ between groups. The between-group difference in MMP-9 activities at week 4 did not reflect different plasma protein levels (P = 0.83). With Robuvit, higher MMP-9 activity correlated with lower TEAC (P = 0.0207); for placebo, it did not (P = 0.1883). MMP-2 activity was higher in both groups at weeks 4 and 8, with no significant difference between groups. There was no correlation between stress markers and significantly changed SF-36 week 4 scores. Postsurgical analgesics were used considerably less with Robuvit.
The results indicate Robuvit significantly improved convalescence and recovery in the first four weeks after hysterectomy. Among limitations noted is the possible formation of different Robuvit compound metabolites due to varying individual food choices and antibiotics, possibly resulting in different gut bacteria. Larger studies are needed of Robuvit's possible general postsurgical benefits.
The authors declared no conflicts of interest.