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Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial

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Abstract

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D3 and 500 μg vitamin K1, twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D3 and vitamin K1 produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

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References

  1. Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 319:516–518

    Article  CAS  PubMed  Google Scholar 

  2. Boyce BF, Aufdemorte TB, Garrett IR, Yates AJ, Mundy GR (1989) Effects of interleukin-1 on bone turnover in normal mice. Endocrinology 125:1142–1150

    Article  CAS  PubMed  Google Scholar 

  3. Gowen M, Wood DD, Ihrie EJ, McGuire MK, Russell RG (1983) An interleukin 1 like factor stimulates bone resorption in vitro. Nature 306:378–380

    Article  CAS  PubMed  Google Scholar 

  4. Ishimi Y, Miyaura C, Jin CH, Akatsu T, Abe E, Nakamura Y, Yamaguchi A, Yoshiki S, Matsuda T, Hirano T et al (1990) IL-6 is produced by osteoblasts and induces bone resorption. J Immunol 145:3297–3303

    CAS  PubMed  Google Scholar 

  5. Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev CD004523

  6. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev CD001155

  7. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev CD003376

  8. Lamb JJ (2006) Osteoporosis. In: Kohlstadt I (ed) scientific evidence for musculoskeletal, bariatric, and sports nutrition. CRC Press, Boca Raton, pp 473–490

  9. Lanham-New SA (2008) Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc 67:163–176

    Article  CAS  PubMed  Google Scholar 

  10. Cashman KD (2007) Diet, nutrition, and bone health. J Nutr 137:2507S–2512S

    CAS  PubMed  Google Scholar 

  11. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642

    Article  CAS  PubMed  Google Scholar 

  12. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683

    Article  CAS  PubMed  Google Scholar 

  13. Tucker KL, Chen H, Hannan MT, Cupples LA, Wilson PW, Felson D, Kiel DP (2002) Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. Am J Clin Nutr 76:245–252

    CAS  PubMed  Google Scholar 

  14. Prynne CJ, Mishra GD, O’Connell MA, Muniz G, Laskey MA, Yan L, Prentice A, Ginty F (2006) Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Am J Clin Nutr 83:1420–1428

    CAS  PubMed  Google Scholar 

  15. Xu L, Dibley M, D’Este C, Phillips M, Porteous J, Attia J (2009) Food groups and risk of forearm fractures in postmenopausal women in Chengdu, China. Climacteric 12:222–229

    Article  CAS  PubMed  Google Scholar 

  16. Rosato MT, Schneider SH, Shapses SA (1998) Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in noninsulin-dependent diabetes mellitus. Calcif Tissue Int 63:107–111

    Article  CAS  PubMed  Google Scholar 

  17. Cashman KD (2008) Altered bone metabolism in inflammatory disease: role for nutrition. Proc Nutr Soc 67:196–205

    Article  CAS  PubMed  Google Scholar 

  18. Konda VR, Desai A, Darland G, Bland JS, Tripp ML (2009) Rho iso-alpha acids from hops inhibit the GSK-3/NF-kappaB pathway and reduce inflammatory markers associated with bone and cartilage degradation. J Inflamm (Lond) 6:26

    Article  CAS  Google Scholar 

  19. Hall AJ, Babish JG, Darland GK, Carroll BJ, Konda VR, Lerman RH, Bland JS, Tripp ML (2008) Safety, efficacy and anti-inflammatory activity of rho iso-alpha-acids from hops. Phytochemistry 69:1534–1547

    Article  CAS  PubMed  Google Scholar 

  20. Tripp M, Konda VR, Hall A, Desai A, Carroll B, Darland G, Lerman R, Emma D, Bland JS (2006) Rho iso-alpha acids, a modified hop (Humulus lupulus) extract, inhibits protein kinases involved in autoimmune disease. FASEB J. 20:A1125

  21. Kuo CL, Chi CW, Liu TY (2004) The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 203:127–137

    Article  CAS  PubMed  Google Scholar 

  22. Lee CH, Chen JC, Hsiang CY, Wu SL, Wu HC, Ho TY (2007) Berberine suppresses inflammatory agents-induced interleukin-1beta and tumor necrosis factor-alpha productions via the inhibition of IkappaB degradation in human lung cells. Pharmacol Res 56:193–201

    Article  CAS  PubMed  Google Scholar 

  23. Qin L, Han T, Zhang Q, Cao D, Nian H, Rahman K, Zheng H (2008) Antiosteoporotic chemical constituents from Er-Xian Decoction, a traditional Chinese herbal formula. J Ethnopharmacol 118:271–279

    Article  CAS  PubMed  Google Scholar 

  24. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559

    Article  CAS  PubMed  Google Scholar 

  25. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2007) Serum insulin-like growth factor-I level is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int 18:1675–1681

    Article  CAS  PubMed  Google Scholar 

  26. Lerman RH, Minich DM, Darland G, Lamb JJ, Schiltz B, Babish JG, Bland JS, Tripp ML (2008) Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial. Nutr Metab (Lond) 5:29

    Article  CAS  Google Scholar 

  27. White MA, Whisenhunt BL, Williamson DA, Greenway FL, Netemeyer RG (2002) Development and validation of the food-craving inventory. Obes Res 10:107–114

    Article  PubMed  Google Scholar 

  28. Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483

    Article  PubMed  Google Scholar 

  29. Greene JG (1998) Constructing a standard climacteric scale. Maturitas 29:25–31

    Article  CAS  PubMed  Google Scholar 

  30. Vasikaran SD (2008) Utility of biochemical markers of bone turnover and bone mineral density in management of osteoporosis. Crit Rev Clin Lab Sci 45:221–258

    Article  CAS  PubMed  Google Scholar 

  31. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  PubMed  Google Scholar 

  32. Cheng S, Suominen H, Vaananen K, Kakonen SM, Pettersson K, Heikkinen E (2002) Serum osteocalcin in relation to calcaneal bone mineral density in elderly men and women: a 5-year follow-up. J Bone Miner Metab 20:49–56

    Article  CAS  PubMed  Google Scholar 

  33. Nabipour I, Larijani B, Jafari SM, Amiri M, Amiri Z (2008) Reference database of CrossLaps and osteocalcin for a healthy Iranian population. Arch Iran Med 11:203–206

    PubMed  Google Scholar 

  34. Ravn P, Rix M, Andreassen H, Clemmesen B, Bidstrup M, Gunnes M (1997) High bone turnover is associated with low bone mass and spinal fracture in postmenopausal women. Calcif Tissue Int 60:255–260

    Article  CAS  PubMed  Google Scholar 

  35. Hu JP, Nishishita K, Sakai E, Yoshida H, Kato Y, Tsukuba T, Okamoto K (2008) Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. Eur J Pharmacol 580:70–79

    Article  CAS  PubMed  Google Scholar 

  36. Wei P, Jiao L, Qin LP, Yan F, Han T, Zhang QY (2009) Effects of berberine on differentiation and bone resorption of osteoclasts derived from rat bone marrow cells. Zhong Xi Yi Jie He Xue Bao 7:342–348

    Article  CAS  PubMed  Google Scholar 

  37. Sakuma M, Endo N, Oinuma T (2007) Serum 25-OHD insufficiency as a risk factor for hip fracture. J Bone Miner Metab 25:147–150

    Article  CAS  PubMed  Google Scholar 

  38. Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K, Okano T (2008) Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab 26:79–85

    Article  CAS  PubMed  Google Scholar 

  39. Kostek MC, Delmonico MJ, Reichel JB, Roth SM, Douglass L, Ferrell RE, Hurley BF (2005) Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol 98:2147–2154

    Article  CAS  PubMed  Google Scholar 

  40. DiGirolamo DJ, Mukherjee A, Fulzele K, Gan Y, Cao X, Frank SJ, Clemens TL (2007) Mode of growth hormone action in osteoblasts. J Biol Chem 282:31666–31674

    Article  CAS  PubMed  Google Scholar 

  41. Yakar S, Kim H, Zhao H, Toyoshima Y, Pennisi P, Gavrilova O, Leroith D (2005) The growth hormone-insulin like growth factor axis revisited: lessons from IGF-1 and IGF-1 receptor gene targeting. Pediatr Nephrol 20:251–254

    Article  PubMed  Google Scholar 

  42. Melmed S, Jameson JL (2008) Disorders of the anterior pituitary and hypothalamus. In Fauci AS et al (eds) Harrison’s principles of internal medicine, chap. 333, McGraw-Hill Professional, New York

  43. Seibel MJ (2005) Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 26:97–122

    PubMed  Google Scholar 

  44. Nimptsch K, Hailer S, Rohrmann S, Gedrich K, Wolfram G, Linseisen J (2007) Determinants and correlates of serum undercarboxylated osteocalcin. Ann Nutr Metab 51:563–570

    Article  CAS  PubMed  Google Scholar 

  45. Karl PI, Friedman PA (1983) Effects of parathyroid hormone and vitamin D on the renal vitamin K-dependent carboxylating system. J Biol Chem 258:12783–12786

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Lincoln Bouillon for trial supervision, and Michelle Babb, Barbara Schiltz, Mabel Lorenzi-Albe, Cynthia Baxter, Leslie Pilkington, Scott Stockmyer, Julie Triggs, and Lara Wax for technical and clinical assistance. The study was funded by Metagenics Inc.

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Correspondence to Joseph J. Lamb.

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M. F. Holick and J. J. Lamb contributed equally.

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Holick, M.F., Lamb, J.J., Lerman, R.H. et al. Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial. J Bone Miner Metab 28, 342–350 (2010). https://doi.org/10.1007/s00774-009-0141-z

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  • DOI: https://doi.org/10.1007/s00774-009-0141-z

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