Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism – a randomised controlled study

Abstract

Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (βCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in βCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in βCTX in the SPI group with the reduction in HbA1c (r 2 = 0.42; p = 0.04) and HOMA-IR (r 2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.There is substantial epidemiological evidence that people with T2DM has increased risk of fractures 1,2 . This increase in fracture risk occurs despite bone mineral density (BMD) being comparatively higher in those with T2DM than those without. In a meta-analysis, Vestergaard reported an increased Z-score of 0.41 at the spine and 0.27 at the hip associated with T2DM 2 . T2DM has been shown to be an independent risk factor for fractures, which is not attributable to increased body mass index (BMI) or other classical osteoporosis risk factors 3 .Testosterone is anabolic for bone primarily through its aromatization to estrogen in adipose tissue 4 . Low testosterone in the setting of low or inappropriately normal luteinizing hormone and follicle-stimulating hormone is common in the diabetes population and may contribute to impaired bone strength in these men with T2DM 5 .Production and consumption of soy foods within Western countries have increased dramatically with postulated health benefits including improvement in bone health, especially in women 6 . Habitual intake of soy isoflavones has also been associated with a reduced risk of T2DM and cardiovascular disease (CVD) 7 .Bone turnover markers (BTMs) are biomarkers for fracture risk that have been used for the evaluation of effects of osteoporosis treatments, and include both bone resorption markers (e.g. type I collagen crosslinked Beta C-telopeptide (βCTX)) and bone formation markers (e.g. type I procollagen-N-propeptide (PINP)). Hypogonadal men with type 2 diabetes have smaller bone size and lower bone turn over 8 . We conducted this analysis to study the effect of soy isoflavone supplementation on BTMs in men with T2DM and low testosterone levels (<12 nmol/L).

Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

“…A significant linear correlation was also shown between βCTX reduction and glycated hemoglobin (HbA1) reduction. These results showed that the intake of soybean proteins containing isoflavones uses a mechanism to reduce βCTX related to blood glucose control and insulin tolerance enhancement by altering insulin resistance [225,226]. This confirmed that by altering insulin resistance in males with type 2 diabetes, the consumption of soy protein containing isoflavones for 3 months reduced βCTX, which is associated with the improvement of blood sugar control and insulin resistance [225].…”

“…These results showed that the intake of soybean proteins containing isoflavones uses a mechanism to reduce βCTX related to blood glucose control and insulin tolerance enhancement by altering insulin resistance [225,226]. This confirmed that by altering insulin resistance in males with type 2 diabetes, the consumption of soy protein containing isoflavones for 3 months reduced βCTX, which is associated with the improvement of blood sugar control and insulin resistance [225]. The intake of soy isoflavones, furthermore, improves the blood glucose level and lowers the risk factors in type 2 diabetes patients.…”

Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers

“…37 Although several long-term RCTs (>6 months) indicated the remarkable effect of soy on BTMs, 41,42 clinical trials with shorter duration (50 days to 6 months) than our study also reported a significant effect on bone remodeling markers. 43,44 Soy isoflavones show weak estrogenic activity with an effectiveness that is incomparable with that of medications for osteoporosis. Thus, long duration is required to acquire favorable effect on the bone remodeling process.…”

Genistein prevents bone loss in type 2 diabetic rats induced by streptozotocin

“…As a phytoestrogen, numerous studies have focused on that genistein prevents bone loss and improve bone health through estrogen receptor pathway in both postmenopausal women and ovariectomized animals ( 18 ). Recently, an epidemiological study suggested that soy-containing isoflavones could reduce bone resorption significantly in men with T2DM, which correlated with an improvement of glycemic control ( 19 ). A small number of animal studies reported that genistein could enhance bone health of animals with T2DM and increase the bone strength ( 20 , 21 ).…”