Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

Min-Yu Tu, Hsiao-Ling Chen, Yu-Tang Tung, Chao-Chih Kao, Fu-Chang Hu, Chuan-Mu Chen, Min-Yu Tu, Hsiao-Ling Chen, Yu-Tang Tung, Chao-Chih Kao, Fu-Chang Hu, Chuan-Mu Chen

Abstract

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients.

Trial registration: ClinicalTrials.gov NCT02361372.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram of patient recruitment…
Fig 1. Flow diagram of patient recruitment and follow-up.
Fig 2. Effects of kefir consumption on…
Fig 2. Effects of kefir consumption on clinical assessment in osteoporotic patients.
(A) Serum calcium. (B) Parathyroid hormone (PTH). (C) β C-Terminal telopeptide of type I collagen (β-CTX). (D) Osteocalcin. (E) Spine bone mineral density (BMD). (F) Femoral neck BMD. (G) Total hip BMD. *P < 0.05 vs. control group.

References

    1. Ager JW III, Balooch G, Ritchie RO. Fracture, aging, and disease in bone. J Mater Res 2006; 21: 1878–1892.
    1. Rubin MA, Jasiuk I, Taylor J, Rubin J, Ganey T, Apkarian RP. TEM analysis of the nanostructure of normal and osteoporotic human trabecular bone. Bone 2003; 33: 270–282.
    1. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332: 305–311.
    1. Laurent Benhamou C. Bone ultrastructure: evolution during osteoporosis and aging. Osteoporos Int 2009; 20: 1085–1087. 10.1007/s00198-009-0867-4
    1. Zioupos P, Currey JD. Changes in the stiffness, strength, and toughness of human cortical bone with age. Bone 1998; 22: 57–66.
    1. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006; 17: 1726–1733.
    1. Sambrook P, Cooper C. Osteoporosis. Lancet 2006; 367: 2010–2018.
    1. Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N, Tannenbaum S. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990; 323: 878–883.
    1. Suleiman S, Nelson M, Li FM, Buxton-Thomas M, Moniz C. Effect of calcium intake and physical activity level on bone mass and turnover in healthy, white, postmenopausal women. Am J Clin Nutr 1997; 66: 937–943.
    1. McKane WR, Khosla S, Egan KS, Robins SP, Burritt MF, Riggs BL. Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. J Clin Endocrinol Metab 1996; 81: 1699–1703.
    1. Ammann P. Bone strength and ultrastructure. Osteoporos Int 1996; 20: 1081–1083.
    1. Takada Y, Aoe S, Kumegawa M. Whey protein stimulates proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Bioph Res Commun 1996; 223: 445–449.
    1. Takada Y, Kobayashi N, Matsuyama H, Kato K, Yamamura J, Yahiro M, et al. Whey protein suppresses the osteoclast-mediated bone resorption and osteoclast cell formation. Int Dairy J 1997; 7: 821–825.
    1. Ammann P, Bonjour JP, Rizzoli R. Essential amino acid supplements increase muscle weight, bone mass and bone strength in adult osteoporotic rats. J Musculoskelet Neuronal Interact 2000; 1: 43–44.
    1. Heaney RP. Calcium, dairy products and osteoporosis. J Am Coll Nutr 2000; 19: S83–S99.
    1. Cashman KD. Milk minerals (including trace elements) and bone health. Int Dairy J 2006; 16: 1389–1398.
    1. Bouhallab S, Bouglé D. Biopeptides of milk: Caseinophosphopeptides and mineral bioavailability. Reprod Nutr Dev 2004; 44: 493–498.
    1. Scholz-Ahrens KE, Schrezenmeir J. Effects of bioactive substances in milk on mineral and trace element metabolism with special reference to casein phosphopeptides. Br J Nutr 2000; 84: S147–S153.
    1. Sato R, Noguchi T, Naito H. Casein phosphopeptide (CPP) enhances calcium absorption from the ligated segment of rat small intestine. J Nutr Sci Vitaminol (Tokyo) 1986; 32: 67–76.
    1. Meisel H, Bockelmann W. Bioactive peptides encrypted in milk proteins: proteolytic activation and thropho-functional properties. Antonie Van Leeuwenhoek 1999; 76: 207–215.
    1. Erba D, Ciappellano S, Testolin G. Effect of the ratio of casein phosphopeptides to calcium (w/w) on passive calcium transport in the distal small intestine of rats. Nutrition 2002; 18: 743–746.
    1. Bennett T, Desmond A, Harrington M, McDonagh D, FitzGerald R, Flynn A, et al. The effect of high intakes of casein and casein phosphopeptide on calcium absorption in the rat. Br J Nutr 2000; 83: 673–680.
    1. Narva M, Nevala R, Poussa T, Korpela R. The effect of Lactobacillus helveticus fermented milk on acute changes in calcium metabolism in postmenopausal women. Eur J Nutr 2004; 43: 61–68.
    1. Adolphi B, Scholz-Ahrens KE, de Vrese M, Acil Y, Laue C, Schrezenmeir J. Short-term effect of bedtime consumption of fermented milk supplemented with calcium, inulin-type fructans and caseinphosphopeptides on bone metabolism in healthy, postmenopausal women. Eur J Nutr 2009; 48: 45–53. 10.1007/s00394-008-0759-y
    1. Chen HL, Tung YT, Tsai CL , Lai CW, Tsai HC , Lin YL, et al. Kefir improves fatty liver syndrome through inhibited lipogenesis pathway in leptin-deficient ob/ob knockout mice. Int J Obesity 2014; 38: 1172–1179.
    1. Chen HL, Tung YT, Chuang CH, Tu MY, Tsai TC, Chang SY, et al. Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis. Osteoporosis Int 2015; 26: 589–599.
    1. Chang YT, Chen CM, Tu MY, Chen HL, Chang SY, Tsai TC, et al. Effects of osteoporosis and nutrition supplements on structures and nanomechanical properties of bone tissue. J Mechan Behav Biomed Materi 2011; 4: 1412–1420.
    1. Tung YT, Tang TY, Chen HL, Yang SH, Chong KY, Chen CM. Lactoferrin protects against chemical-induced rat liver fibrosis through inhibiting stellate cells activation. J Dairy Sci 2014; 97: 3281–3291. 10.3168/jds.2013-7505
    1. Black RE, Williams SM, Jones IE, Goulding A. Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health. Am J Clin Nutr 2002; 76: 675–680.
    1. Hu JF, Zhao XH, Jia JB, Parpia B, Campbell TC. Dietary calcium and bone density among middle-aged and elderly women in China. Am J Clin Nutr 1993; 58: 219–227.
    1. Murphy S, Khaw KT, May H, Compston JE. Milk consumption and bone mineral density in middle aged and elderly women. Br Med J 1994; 308: 939–941.
    1. Recker RR, Heaney RP. The effect of milk supplements on calcium metabolism, bone metabolism and calcium balance. Am J Clin Nutr 1985; 41: 254–263.
    1. Matkovic V, Landoll JD, Badenhop-Stevens NE, Ha EY, Crncevic-Orlic Z, Li B, et al. Nutrition influences skeletal development from childhood to adulthood: a study of hip, spine, and forearm in adolescent females. J Nutr 2004; 134: S701–S705.
    1. Uenishi K, Ishida H, Toba Y, Aoe S, Itabashi A, Takada Y. Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women. Osteoporos Int 2007; 18: 385–390.
    1. Möller NP, Scholz-Ahrens KE, Roos N, Schrezenmeir J. Bioactive peptides and proteins from foods: indication for health effects. Eur J Nutr 2008; 47: 171–182. 10.1007/s00394-008-0710-2
    1. Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R. The effect of calcium supplementation on the circadian-rhythm of bone resorption. J Clin Endocrinol Metabol 1994; 79: 730–735.
    1. Horowitz M, Need AG, Morris HA, Wishart J, Nordin BE. Biochemical effects of calcium supplementation in postmenopausal osteoporosis. Eur J Clin Nutr 1988; 42: 775–778.
    1. Martini L, Wood RJ. Relative bioavailability of calcium-rich dietary sources in the elderly. Am J Clin Nutr 2002; 76: 1345–1350.
    1. Matkovic V, Heaney RP. Calcium balance during human growth: evidence for threshold behavior. Am J Clin Nutr 1992; 55: 992–996.
    1. Reeves RE, Latour NG. Calcium phosphate sequestering phosphopeptide from casein. Science 1958; 128: 472
    1. Naito H, Suzuki H. Further evidence for the formation in vivo of phosphopeptide in the intestinal lumen from dietary beta-casein. Agric Biol Chem 1974; 38: 1543–1545.
    1. Riggs BL, O’Fallon WM, Muhs J, O’Connor MK, Kumar R, Melton LJ III. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 1998; 13: 168–174.
    1. Scholz-Ahrens KE, Barth CA, Drescher K, Goralczyk R, Rambeck WA, Wehr U, et al. Modulation of bone markers by dietary calcium in ovariectomized minipigs. Osteoporos Int 1996; 6: S242.
    1. Scholz-Ahrens KE, de Vrese M, Barth CA. Influence of casein-derived phosphopeptides on the bioavailability of calcium in vitamin D-deficient miniature pigs In: Norman AW, Bouillon R, Thomasset M. Vitamin D, gene regulation, structure-function analysis and clinical application. Berlin: Walter de Gruyter; 1991; pp. 724–725.
    1. Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85: 3069–3076.

Source: PubMed

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