Preliminary Evidence Hints at a Protective Role for Boron in Urolithiasis

Dear Editor:

Stone disease is an increasingly common form of renal disease that is associated with crystal deposition in the renal medulla in all cases studied so far. Therapy to prevent stones is based on lowering supersaturation, using both diet and medication.

Boron seems to have an impact on stone removal, dissolving, or passing out with pain alleviation and cease of hematuria. Therefore, in our study 14 patients with urolithiasis, confirmed by ultrasonography, were investigated.

Urolithiasis is a multifactorial disorder influenced by both intrinsic and environmental factors. There is some initial experimental evidence to implicate sex hormones in the pathogenesis of stone disease. ¹ To reduce the incidence, it must be considered that the urine composition is directly related to diet. ² Recently, boron has attracted much attention, and foods of plant origin, especially fruits, leafy vegetables, nuts, and legumes, are rich in boron, as are wine, cider, and beer. ³

To initiate a link between boron and urolithiasis, 2 decades ago, a 27-year-old man who voluntarily had participated in a study was reported to have discarded and collected a 2.0-mm urinary stone, after consuming 10.0 mg boron for 3 days.

Thus, the aim of this preliminary investigation was to evaluate the effect of boron supplementation on removal/treatment of kidney stones. It was speculated that alterations in steroid hormone concentrations by boron may have an impact on stone removal.

Fourteen (14) volunteer patients whose urolithiasis was confirmed by ultrasonography method were referred and admitted to receive a 10-mg boron supplement per day in the form of capsules. The capsules were formulated and provided by a pharmacist colleague, using sodium tetraborate as the source of boron. Patients had an ultrasonography report confirming the presence of kidney stone(s). They were asked to consume enough servings of dairy products plus adequate liquids and were allowed to withdraw any time they wished. The period of boron consumption and the details of the reports are presented as case series in Table 1.

The patients' characteristics and the description of the stones are presented in Table 1. All cooperated and completed their course of treatment (only 2 discontinued the follow-up) and the pre- and postultrasonography assessment were performed in the same center. The patients reported pain alleviation and cease of hematuria (if present) within hours to 2–3 days after consumption, and mostly at the time of discarding their stone. Most subjects reported that there was no discard and apparently it has been dissolved or passed out easily. No adverse outcomes were reported for supplement intake.

Most of the patients reported having a sensation of renal colic or ureteral spasm after boron supplementation and reasonable pain alleviation.

In order for crystals to form, urine must be supersaturated with respect to the stone material, meaning that concentrations are higher than the thermodynamic solubility for that substance. Levels of urinary supersaturation correlate with the type of stone formed. ⁴ For CaOx, the most important determinants of urinary supersaturation are total daily calcium excretion and urine volume: in other words, urine calcium concentration. ^5,6 It is reported that boron supplementation of 3 mg/day decreased urinary Ca and P excretion in humans. ⁷

Foods particularly rich in boron include avocado, peanuts, pecans, grapes, raisins, and wine. Legumes, nuts, and avocados contain 1.0–4.5-mg boron/100 g. ³ Absorption appears to be virtually complete (95% in humans and rats) and boron is excreted largely in the urine. ⁸ The Food and Nutrition Board of the Institute of Medicine has established the Tolerable Upper Intake Level for adults over 18 years old as 20 mg/day. ⁹

The association between serum testosterone and urolithiasis as a specific underlying risk factor has so far received only limited attention. In particular, Kato et al. (2005) concluded that menopausal women might have an increased potential for urinary stone formation compared with premenopausal women. ¹⁰

Testosterone appears to promote stone formation by suppressing renal osteopontin expression and increasing urinary oxalate excretion, while estrogen appears to inhibit stone formation by increasing osteopontin expression in the kidneys and decreasing urinary oxalate excretion. ¹¹ Active dihydrotestosterone is partially responsible for exaggerated hyperoxaluria observed in the rat ethylene glycol model of urolithiasis. ¹

Recent findings indicate that boron and borates may possess anticarcinogenic properties. ¹² Hormone replacement therapy (HRT) is known to reduce lung cancer, and dietary boron may have actions similar to those of HRT. ¹³ Nielsen et al. (1987) indicated that dietary boron repletion in postmenopausal women, who were previously on a low-boron diet, increased their serum 17B-estradiol (E2) and testosterone levels. ⁷ Similar significant increase in serum E2 levels was found in healthy males after 4 weeks of boron supplementation. ¹⁴ Therefore, one possible proposed mechanism is the conversion of T to E2 by boron.

Urinary excretion of tumor necrosis factor-α (TNF-α) increased from the lithotripsy-treated kidney by 1 hour after treatment, ¹⁵ and an increase was noted in TNF-α, interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and serum amyloid A in percutaneous nephrolithotomy. ¹⁶

Furthermore, in a study, 1-week boron supplementation resulted in a significant decrease in plasma TNF-α concentration (12.32 versus 9.97 pg/mL) and a remarkable decrease (about 50%) in plasma concentration of high sensitive C reactive protein (hsCRP) (1460 versus 795 ng/mL) and IL-6 (1.55 versus 0.87 pg/mL) in healthy male subjects, respectively. ¹⁷

Moreover, it sounds reasonable to speculate that alterations in steroids by boron, and the reduction of cytokines with a possible change in urine calcium concentration may have an impact on the prevention of stone formation or removal. Successful and comfortable kidney stone repulsion with minor pain and bleeding indicates that this impact of boron requires and deserves further investigations, which will require the cooperation of urologists to clarify and confirm the above finding. Therefore, more clinical trials are needed to establish the usefulness of boron in the adjunctive treatment of urolithiasis.