- Email: [email protected]
Inulin and oligofructose as functional ingredients to improve bone mineralization
ARTICLE IN PRESS
International Dairy Journal 16 (2006) 1092–1097 www.elsevier.com/locate/idairyj
Review
Inulin and oligofructose as functional ingredients to improve bone mineralization D. Bosscher, J. Van Loo, A. Franck Orafti, Tiense Suikerraffinaderij, Aandorenstraat 1, 3300 Tienen, Belgium Received 4 May 2005; accepted 6 October 2005
Abstract Studies in animal models have shown increased calcium availability with inulin and oligofructose in the diet. This possibly beneficial effect of inulin-type fructans on the delay of osteoporosis was further evaluated in rats and it was found that accumulation of bone mineral and formation of improved trabecular network structure were indeed stimulated. In ovari-ectomized rats, oligofructose increased bone mineral content (BMC) and impeded ovari-ectomy induced loss of bone structure. These findings support the hypotheses that inulin and oligofructose might influence peak bone mass during adolescence in humans. Studies in girls with a high habitual calcium intake showed increased calcium absorption after supplementation of an oligofructose-enriched inulin (8 g d1) in the diet. This effect was highest in girls showing a habitual low degree of calcium absorption. Recently, a 1 y intervention trial on pre-pubertal girls and boys (n ¼ 100) found significantly increased calcium absorption in the group receiving oligofructose-enriched inulin (8 g d1) after 8 wks and the effect lasted during the whole intervention period, resulting in improved BMC and significantly increased bone mineral density compared to the controls. r 2006 Elsevier Ltd. All rights reserved. Keywords: Inulin; Oligofructose; Prebiotics; Calcium absorption; Bone mineralization
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effects on calcium absorption and bone mineralization in animals . . . . 2.1. Low, medium and high calcium diets . . . . . . . . . . . . . . . . . . . . 2.2. Combination of short and long-chain inulin-type fructans . . . . . 3. Effects on calcium absorption and bone mineralization in humans . . . . 3.1. Short-term studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Long-term studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Relevance of the data compared with current calcium strategies . 4. Effects on reduction of osteoporosis risk . . . . . . . . . . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
1092 1093 1093 1094 1094 1094 1095 1095 1096 1096 1097
1. Introduction
Corresponding author. Tel.: +32 16 801 268; fax: +32 16 801 359.
E-mail address: [email protected] (D. Bosscher). 0958-6946/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.idairyj.2005.10.028
Nutritional factors influence skeletal development during growth and bone maintenance during adulthood. Therefore, nutrition plays an important role in the pathophysiological process of osteoporosis. Osteoporosis is
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
acknowledged as one of the leading health care problems in the world and about one in three post-menopausal women and a substantial number of men above 50 will have an osteoporosis-related fracture at some point (Consensus Development Statement, 1997). Among nutrients with potential impact on bone health, most attention has been focused on calcium and bone mineral accrual. During childhood and adolescence adequate calcium intakes contribute to achieve peak bone mass between the ages of 20 and 25. After a decade or so in which bone mass remains more or less constant, loss of bone tissue and of calcium begins to occur and becomes significant as ageing processes. In particular, loss of bone in women accelerates in the years immediately after the menopause. The young woman’s skeleton has a bone mineral content (BMC) of about 2200 g, of which 32% or 708 g is elemental calcium (Ellis, Shypailo, Hergenroeder, Perez, & Abrams, 1996). This amount must be accumulated over the first 20 y of life at an average accretion rate of 35 g y1 or 97 mg d1 (Parfitt, 1994). This mean value obscures the considerable variability in rate of calcium uptake during growth of the skeleton, especially during adolescence. Pubertal growth spurt is associated with a rapid increase in calcium gain by the skeleton corresponding with higher rates of dietary calcium absorption and of kinetically determined bone calcium deposition in the bone than those in pre-puberty or adulthood. Abrams et al. (2000) found higher calcium absorption, bone calcium deposition rate (calcium gain) and markers of bone metabolism in the late pre-pubertal and the pubertal period (Tanner stage 2) (average calcium gain 110745 and 135753 mg d1, respectively). According to Martin, Bailey, McKay, and Whiting (1997) the highest rate of calcium gain is around 174 mg d1 for boys and 212 mg d1 for girls and lags about 1–1.5 y behind the age at which growth velocity reaches its peak at the age of 13.3 y for boys and 11.4 y for girls. In the study of Hui, Johnston, and Mazess (1985) peak rates of calcium accretion were about 160 mg d1 for girls (12 y old) and 200 mg d1 for boys (16 y of age). Calcium intake influences mineral accrual in growing children. However, optimal calcium uptakes in school-aged children are rarely attained (Alaimo, McDowel, & Briefel, 1994). This inadequate supply of calcium to the rapidly expanding skeletal volume might result into a suboptimal amount of bone mineral per unit of skeletal volume. Skeletal fragility is considered a major cause of the high incidence of forearm fractures in children near the age at which growth velocity reaches its maximum and the bones are growing at their fastest rate (Goulding et al., 1998; Goulding, Jones, Taylor, Manning, & Williams, 2000; Parfitt, 1994). This bone mineral deficit due to rapid skeletal growth might have also implications later in life, e.g. osteoporosis. Active ingredients such as inulin and oligofructose, are gaining more and more attention because they improve calcium absorption from the diet. High absorption of
1093
calcium from the diet increases peak bone mass and therefore might postpone the risk of osteoporosis-induced fractures at older age. In this perspective, inulin and oligofructose can play a relatively important role in the prevention of osteoporosis from infancy to the last decade of life. Inulin and oligofructose are prebiotic fibres obtained from the chicory root (Cichorium intybus) and are composed of b(2-1) linked fructose units, schematically given as GFn and Fn (G ¼ glucose, F ¼ fructose and n ¼ number of F-units). Native inulin encompasses a family of linear structures (GFn) varying in degree of polymerization (DP) from 3 to 60 (average DP ¼ 10). Oligofructose is obtained by partial hydrolysis of inulin and has a small DP ranging from 2 to 8 (average DP ¼ 4). Prebiotics are non-digestible food ingredients that are beneficial for the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can improve the host’s health (Gibson, Probert, Van Loo, Rastall, & Roberfroid, 2004). Inulin and oligofructose are not digested and reach the colon intact where they are fermented by the microflora, particularly by the endogenous lactic acid bacteria (LAB), bifidobacteria and lactobacilli (Gibson, Beatty, & Cummings, 1995; Kleessen, Sykura, Zunft, & Blaut, 1997; Langlands, Hopkins, Coleman, & Cummings, 2004; Menne, Guggenbuhl, & Roberfroid, 2000; Rao, 2001; Tuohy, Finlay, Wynne, & Gibson, 2001; Tuohy, Kolida, Lustenberger, & Gibson, 2001). The aim of this paper is to review current evidence on the effects of the prebiotics inulin and oligofructose on calcium absorption and bone metabolism and to provide state of the art information on the role of inulin and oligofructose in improving long-term bone health. Description of the mechanisms by which inulin and oligofructose influence calcium (and magnesium) absorption is given by Scholz-Ahrens and Schrezenmeir (2002) and by Weaver (2005). 2. Effects on calcium absorption and bone mineralization in animals 2.1. Low, medium and high calcium diets Over the past 10 y, experiments in animal models have repeatedly shown that inulin and oligofructose increase calcium absorption from the diet. First experiments performed in growing rats found a significant higher apparent calcium absorption after 25 days by addition of 10% native inulin or oligofructose to the diet compared with placebo (respectively, 40% or 43% vs. 25% apparent calcium retention) (Po0:05). The animals in this study were fed a standard diet with normal calcium levels (0.7%) (Delzenne, Aertssens, Verplaetse, Roccaro, & Roberfroid, 1995). This change in calcium absorption from diets supplemented with inulin-type fructans was further evaluated by determining the effect of three experimental diets (low,
ARTICLE IN PRESS 1094
D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
medium and high in calcium) on bone health in growing rats. Four weeks old rats were randomized into 9 different groups receiving 0% (control), 5% or 10% long-chain inulin with 0.2%, 0.5%, or 1% calcium in their respective diets. The trial lasted for 22 wks during which parameters of bone mineralization were measured at four different time points (10, 14, 18, 22 wks). From wk 10 to wk 22, in all three calcium groups fed the two levels of inulin (5% and 10%), changes in whole body BMC (WBBMC) (P ¼ 0:02) and in whole body bone mineral density (WBBMD) were significant as compared with those in the controls (Po0:001). Long-term inulin administration resulted in more accumulation of bone mineral and improved structure of the trabecular network in rats fed low, medium, or high calcium diets (Roberfroid, Cumps, & Devogelaer, 2002). Whether the improved calcium absorption seen with inulin-type fructans also led to the postponement or prevention of osteoporosis was further investigated in adult ovariectomised rats (animal model for post-menopausal women) fed with diets containing normal (0.5%) and high (1%) calcium levels. The semi-purified diets contained moreover either 10% or no (control) oligofructose . After 16 wks, bone calcium content in the femur was significantly increased in both oligofructose supplemented groups (normal and high calcium level in diet) as compared to both control groups (Po0:05). Calcium content in the lumbar vertebra was also increased in the oligofructose supplemented group fed with high calcium diet as compared to that in the corresponding control group (Po0:05). Moreover, the oligofructose supplementation of the diets impeded ovariectomy induced loss of bone (trabecular) structure in tibia irrespective of the calcium content of the diets (Scholz-Ahrens, Ac- il, & Schrezenmeir, 2002). 2.2. Combination of short and long-chain inulin-type fructans In a subsequent study it was aimed to investigate the effects of inulin-type fructans with different chain lengths and what the effect would be of a combination of both short and long-chain inulins. Adult rats were fed a normal calcium diet (0.5%) supplemented with 10% long-chain inulin, 10% oligofructose, or 10% of a blend of oligofructose and long-chain inulin (oligofructose-enriched inulin), or a non-supplemented diet (control). After 4 wks, calcium absorption improved in all fructan supplemented diets. Applying the oligofructose-enriched inulin did not only increase the apparent calcium absorption but also the calcium balance significantly. Values for calcium absorption were 58.177.4% and 47.975.5% of apparent absorption (Po0:05), whereas those for calcium balance were 58.578.2 and 46.876.3 mg d1 (Po0:05) in the oligofructose-enriched inulin group and the control group, respectively. It appeared that a synergistic effect was obtained by combining the short with the long-chain
inulin-type fructan fractions with respect to calcium absorption (Coudray, Tressol, Gueux, & Rayssiguier, 2003). Details on the composition of this synergistically active mixture of oligofructose and long-chain inulin (abbreviated as SYN1) are described by Van Loo (2004). The improved functionality of the SYN1 led to the setup of short-term studies to evaluate the effect of SYN1 on calcium kinetics in ovariectomised rats by catheterization of (jugular) veins after 45Ca administration (orally). Rats that were fed semi-purified diets containing only 5% of SYN1 during 21 d showed significantly increased calcium absorption (Po0:005), bone retention (Po0:005), femoral calcium content (Po0:05) and femoral BMD (Po0:05) compared to the control rats. Moreover, kinetic data on bone metabolism showed improved bone balance and suppression of bone turnover (Zafar, Weaver, Zhao, Martin, & Wastney, 2004). 3. Effects on calcium absorption and bone mineralization in humans 3.1. Short-term studies To evaluate the effect of SYN1 on calcium absorption during adolescence, human intervention trials were undertaken by measuring true calcium absorption using dual stable isotope analysis techniques (46Ca/42Ca) in urine collected during 48 h. Twenty-nine adolescent girls (11–13 y old) were randomized in a double-blind manner and their calcium status was followed for 2 times 3 wks (2 wks washout between treatments) in a crossover intervention study. Girls had calcium intakes of 1300–1500 mg d1 and were supplemented with 8 g d1 of SYN1 or with sucrose (placebo) added to calcium-fortified orange juice. True calcium absorption was significantly higher in the group receiving SYN1 (38.2%79.8%) than in the placebo treatment (32.3%79.8%) (P ¼ 0:01) (Griffin et al., 2002). It appeared that consumption of 8 g d1 of SYN1 added to the daily diet significantly improved calcium absorption in girls with normal habitual calcium intakes. However, to further evaluate the subject characteristics that are associated with this beneficial effect, an additional 25 newly recruited girls were enrolled in a second study. Globally, it was a two-center study (Houston, Texas and Omaha, Nebraska) with a total of 54 adolescent girls (av. 12.4 y old). Overall, the data confirmed the significant increase in calcium absorption observed earlier with SYN1 (36.179.8%) compared with the placebo (33.179.2%; P ¼ 0:027). The most consistent identifiable determinant of a beneficial effect of SYN1 on calcium absorption was the fractional calcium absorption during the placebo period, with those individuals with lower calcium absorption during the placebo period showing the greatest increase in calcium absorption in response to SYN1. This finding is important as these girls might be most likely to benefit from SYN1 supplementation to their daily diet (Griffin, Hicks, Heaney, & Abrams, 2003). Since the subjects
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
A long-term intervention trial was recently conducted to determine whether the increased true calcium absorption seen with SYN1 consumption resulted in an additional net mineral accretion in bone in pubertal girls and boys (Tanner stage 2 and 3), since calcium accretion is at its optimal stage during the pubertal ages and its level determines bone health at later age. Randomized girls were all pre-menarcheal since calcium retention tends to be maximal at this stage and lowers at post-menarcheal age (Jackman et al., 1997). About 100 girls and boys of 9–12 y old and with normal calcium intakes (900–1000 mg Ca d1) participated in the intervention study that lasted 1 y. They were randomized in a double-blind controlled manner to receive either 8 g d1 of SYN1 or maltodextrin (placebo) added to the diet in a calcium-fortified orange juice or milk. The findings are presented in Figs. 1–3. Subjects enrolled in the SYN1 group had significantly higher true calcium absorption, 38.5%71.2% compared with controls 30.071.3%, already after 8 wks of supplementation (Po0:001). The higher absorption percentage was kept during the whole intervention trial, 37.772.1% for the SYN1 group and 31.772.3% for controls (P ¼ 0:048), respectively. Correspondingly, SYN1 supplemented subjects had a significantly higher change in whole body BMC (WBBMC), 245711 g y1, than controls, 210710 g y1 (P ¼ 0:03). Under the assumption that the fraction of calcium per g BMC is 32%, these values correspond to daily skeletal calcium accretion of 218710 mg d1 for the SYN1 group and 189710 mg d1 for controls (P ¼ 0:04). This leads to a calculation of an additional net accretion of 30715 mg Ca d1. The change in WBBMD was also significantly greater with respect to the SYN1 supplemented subjects, 0.04770.004 g cm2 y1 compared with the controls, 0.03270.004 g cm2 y1 (P ¼ 0:01), with an increment in WBBMD after 1 y of 0.01570.004 g cm2 y1 (Z-score difference ¼ 0.1870.08, P ¼ 0:02) (Abrams et al., 2005). It appears that increased true calcium absorption with 8 g d1 of SYN1 during pubertal growth enhances bone mineralization probably resulting in increased peak bone mass during adolescence. 3.3. Relevance of the data compared with current calcium strategies One might consider what the relevance is of these findings compared with current dietary strategies to improve bone mass during adolescence. Much emphasis
**
* 38.0 True Ca absorption (%)
3.2. Long-term studies
40.0
36.0 34.0 32.0 30.0 oligofructose-enriched inulin
control
28.0 0
4
2
10
6 8 Time (months)
12
Fig. 1. True calcium availability (%) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructoseenriched inulin or maltodextrin (control) for 8 wks and 1 y. * Represent significant difference compared with the controls Po0:001. P ¼ 0:04. (Abrams et al., 2005)
350 300 Change in WBBMC (g y-1)
received very similar test meals, the cause of this variation does not result from the varying presence of enhancers or inhibitors of calcium absorption in the diets, but rather from the subjects’ tanner stages or genotypes of which some are likely to benefit more from SYN1 consumption than others.
1095
* 250 200 150 100 50 0 control
oligofructose-enriched inulin
Fig. 2. Change in whole body bone mineral content (WBBMC) (g y1) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructose-enriched inulin or maltodextrin (control) for 1 y (Abrams et al., 2005).
has been laid on the promotion of high calcium foods (e.g. dairy foods) or the use of calcium supplements to achieve optimal bone formation. Increased consumption of dairy products by pubertal girls with habitual low calcium intakes has indeed found to increase their BMC and bone mass accrual (Chan, Hoffman, & McMurry, 1995). The beneficial effects of supplement use during pubertal age are less clear. Studies in girls receiving calcium supplements on a daily basis during 1 y found only moderate effects on their BMD, without any improvements in the mineral content of the bones. These girls, however, were at menarcheal age and had habitual calcium intakes around recommended levels (Molgaard, Thomsen, & Michaelsen, 2004). Other studies in girls with normal and low calcium intakes and receiving supplements during a long term, did
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
1096 0.06 Change in WBBMD (g cm−2 y−1)
*
comparable to or exceeds that seen in trials of calcium supplementation alone (Molgaard et al., 2004),
0.05
4. Effects on reduction of osteoporosis risk 0.04 0.03 0.02 0.01 0.00 control
oligofructose-enriched inulin
Fig. 3. Change in whole body bone mineral density (WBBMD) (g cm2 y1) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructose-enriched inulin or maltodextrin (control) for 1 y. *Represent significant difference compared with the controls P ¼ 0:01. (Abrams et al., 2005).
found significant effects on bone acquisition at various sites (indicated by increased BMD) (Lloyd et al., 1993; Dodiuk, Rozen, Rennert, Rennert, & Ish-Shalom, 2005; Matkovic et al., 2005). These studies again failed to demonstrate significant changes in BMC with calcium supplementation (Lloyd et al., 1993; Dodiuk et al., 2005). That adequate calcium intake during early adulthood not only has shortterm effects on bone mineralization, but also affects bone health during whole life, is demonstrated by the low skeletal bone-mineral density in adult women who reported low intake of milk in early adulthood compared with those women with medium or high intakes (New, Bolton-Smith, Grubb, & Reid, 1997). It appears that during the phase of rapid growth suboptimal calcium intake is one limiting factor for adequate bone mineralization throughout life. Therefore, strategies to increase the absorption of the ingested calcium may offer another approach to improve bone mineralization on the long term. As reviewed in this manuscript, several wellcontrolled studies in animals found significant higher calcium absorption with inulin, oligofructose or oligofructose-enriched inulin (SYN1) from low, medium or high calcium diets. Randomized human intervention trials (stable isotopes) demonstrated (on average) a 20% (significant) increase in calcium absorption following SYN1 administration to a normal calcium diet. Moreover, that this increased calcium absorption with SYN1 resulted into a higher calcium accretion, BMD and BMC (vs. the control subjects) was recently demonstrated (Abrams et al., 2005). This net benefit in calcium accretion into the skeleton with SYN1 was on average 11 g y1 during the stage pubertal growth. Although it is difficult to compare the data from this study with studies on calcium supplementation since most of these studies involve subjects with low calcium intakes or have different duration (Lloyd et al., 1993), it appears that this extra amount of calcium gain by the skeleton with SYN1 is
At present there are two approaches to prevent osteoporosis. The first is by optimizing bone mass acquisition in the skeleton during adolescent growth, the second is by minimizing bone loss in the post-menopausal period. Inulin and oligofructose might have a role in both. Increasing BMD and BMC with SYN1 could maximize peak bone mass during adolescence thereby reducing skeletal fragility at elder age. It appears that BMD at various sites is a good predictor of hip fractures (Cummings et al., 1993). A population-based cohort study in 7598 elderly women (75 y) found WBBMD to be a significant predictor of hip fracture (Schott et al., 1998). Indeed meta-analysis of prospective cohort studies found that bone density can predict fracture risk, which predictive ability was roughly similar or tended to be better than that of 1 standard deviation (SD) increases in blood pressure for stroke and better than that of 1 SD increases in serum cholesterol concentration for cardiovascular disease (Marshall, Johnell, & Wedel, 1996). Long observational studies are needed to reveal the protective effects of improved BMD during adolescence and the reduced risk of osteoporotic fractures at elder ages. Menopause is a time when estrogen deficiency leads to accelerated bone resorption and negative bone balance. Studies with SYN1 in rat models of the menopause showed increased bone balance and calcium absorption, whereas bone turn-over decreased in ovariectomised rats (Zafar et al., 2004). Other studies with oligofructose using the same rat model, showed that the increased calcium absorption rate following supplementation was translated into a greater calcium content of the femur and lumbar vertebrae. With respect to their bone architecture, oligofructose prevented ovariectomy-induced loss of bone structure (Scholz-Ahrens et al., 2002). These animal data show promising results on the role inulin and oligofructose can play in positively modulating bone mineral metabolism during post-menopausal age and need to be confirmed in human interventions trials which are currently ongoing. 5. Conclusion Consumption of inulin and oligofructose in humans, particularly SYN1, increases calcium absorption and improves both bone mineral content and bone mineral density (BMD) during periods of rapid growth. Rat models of the menopause suggest that increases in calcium absorption translate into a greater BMD following supplementation with inulin and oligofructose. A longterm study in adolescents indicated that substantial bone health benefits arose from SYN1 supplementation of 8 g d1. This has implications for future preventative strategies for osteoporosis.
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
References Abrams, S. A., Copeland, K. C., Gunn, S. K., Gundberg, C. M., Klein, K. O., & Ellis, K. J. (2000). Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls. The Journal of Clinical Endocrinology & Metabolism, 85, 1805–1809. Abrams, S. A., Griffin, I. J., Hawthorne, K. M., Liang, L., Gunn, S. K., Darlington, G., & Ellis, K. J. (2005). A combination of prebiotic shortand long-chain fructans enhances calcium absorption and bone mineralization in young adolescents. American Journal of Clinical Nutrition, 82, 471–476. Alaimo, K., McDowel, M.A., & Briefel, R.R. (1994). Dietary intake of vitamins, minerals and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase I, 1988–1991. Advance Data from Vital and Health Statistics: No. 258. Hyattsville, MD, USA: National Center for Health Statistics. Chan, G. M., Hoffman, K., & McMurry, M. (1995). Effects of dairy products on bone and body composition in pubertal girls. Journal of Pediatrics, 126, 551–556. Consensus Development Statement. (1997). Who are candidates for prevention and treatment of osteoporosis? Osteoporosis International, 2, 285–289. Coudray, C., Tressol, J. C., Gueux, E., & Rayssiguier, Y. (2003). Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats. European Journal of Nutrition, 42, 91–98. Cummings, S. R., Black, D. M., Nevitt, M. C., Browner, W., Cauley, J., Ensrud, K., et al. (1993). Bone density at various sites for prediction of hip fractures. The Lancet, 341, 72–75. Delzenne, N., Aertssens, J., Verplaetse, H., Roccaro, M., & Roberfroid, M. (1995). Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy digestive balance in the rat. Life Sciences, 57, 1579–1587. Dodiuk, R. P., Rozen, G. S., Rennert, G., Rennert, H. S., & Ish-Shalom, S. (2005). Sustained effects of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake. American Journal of Clinical Nutrition, 81, 168–174. Ellis, K. J., Shypailo, R. J., Hergenroeder, A., Perez, M., & Abrams, S. (1996). Total body calcium and bone mineral content: comparison of dial-energy X-ray absorptiometry with neuron activation analysis. Journal of Bone Mineral Research, 11, 843–848. Gibson, G. R., Beatty, E. R., & Cummings, J. (1995). Selective fermentation of Bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology, 108, 975–982. Gibson, G. R., Probert, H. M., Van Loo, J., Rastall, R. A., & Roberfroid, M. B. (2004). Dietary modulation of the human colonic microbiota: Updating the concept of prebiotics. Nutrition Research Reviews, 17, 259–275. Goulding, A., Cannan, R., Williams, S. M., Gold, E. J., Taylor, R. W., & Lewis-Barned, N. J. (1998). Bone mineral density in girls with forearm fractures. Journal of Bone and Mineral Research, 13, 143–148. Goulding, A., Jones, I. E., Taylor, R. W., Manning, P. J., & Williams, S. M. (2000). More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. Journal of Bone and Mineral Research, 15, 2011–2018. Griffin, I. J., Davila, P. M., & Abrams, S. A. (2002). Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes. British Journal of Nutrition, 87, S187–S191. Griffin, I. J., Hicks, P. M. D., Heaney, R. P., & Abrams, S. A. (2003). Enriched chicory inulin increases calcium absorption mainly in girls with lower calcium absorption. Nutrition Research, 23, 901–909. Hui, S. L., Johnston, C. C., & Mazess, R. B. (1985). Bone mass in normal children and young adults. Growth, 49, 34–43. Jackman, L. A., Millane, S. S., Martin, B. R., Wood, O. B., McCabe, G. P., Peacock, M., et al. (1997). Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females. American Journal of Clinical Nutrition, 66, 327–333.
1097
Kleessen, B., Sykura, B., Zunft, H-J., & Blaut, M. (1997). Effects of inulin and lactose on fecal microflora, microbial activity and bowel habit in elderly constipated persons. American Journal of Clinical Nutrition, 65, 1397–1402. Langlands, S. J., Hopkins, M. J., Coleman, N., & Cummings, J. H. (2004). Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut, 53, 1610–1616. Lloyd, T., Andon, M. B., Rollings, N., Martel, J. K., Landis, J. R., Demers, L. M., et al. (1993). Calcium supplementation and bone mineral density in adolescent girls. The Journal of the Amercian Medical Association, 270, 841–844. Menne, E., Guggenbuhl, N., & Roberfroid, M. (2000). Fn-type chicory inulin hydrolysate has a prebiotic effect in humans. Journal of Nutrition, 130, 1197–1199. Martin, A. D., Bailey, D. A., McKay, H. A., & Whiting, S. (1997). Bone mineral and calcium accretion during puberty. American Journal of Clinical Nutrition, 66, 611–615. Marshall, D., Johnell, O., & Wedel, H. (1996). Meta-analysis of how well measures of one mineral density predict occurrence of osteoporotic fractures. British Medical Journal, 312, 1254–1259. Matkovic, V., Goel, P. K., Badenho-Stevens, N. E., Landoll, J. D., Li, B., Ilich, J. Z., et al. (2005). Calcium supplementation and bone mineral density in females from childhood adulthood: A randomised controlled trail. American Journal of Clinical Nutrition, 81, 175–188. Molgaard, C., Thomsen, B. L., & Michaelsen, K. F. (2004). Effect of habitual dietary calcium intake on calcium supplementation on 12–14y-old girls. American Journal of Clinical Nutrition, 80, 1422–1427. New, S. A., Bolton-Smith, C., Grubb, D. A., & Reid, D. M. (1997). Nutritional influences on bone mineral density: A cross-sectional study in premenopausal women. Amercian Journal of Clinical Nutrition, 65, 1831–1939. Parfitt, A. M. (1994). The two faces of growth: Benefits and risks to bone integrity. Osteoporosis International, 4, 382–398. Rao, V. A. (2001). The prebiotic properties of oligofructose at low intake levels. Nutrition Research, 21, 843–848. Roberfroid, M. B., Cumps, J., & Devogelaer, J. P. (2002). Dietary chicory inulin increases whole-body bone mineral density in growing male rats. Journal of Nutrition, 132, 3599–3602. Scholz-Ahrens, K. E., Ac- il, Y., & Schrezenmeir, J. (2002). Effect of oligofructose or dietary calcium on repeated calcium and phosphorus balances, bone mineralization and trabecular structure in ovariectomized rats. British Journal of Nutrition, 88, 365–377. Scholz-Ahrens, K. E., & Schrezenmeir, J. (2002). Inulin, oligofructose and mineral metabolism—experimental data and mechanism. British Journal of Nutrition, 87, S179–S186. Schott, A. M., Cormier, C. C., Favier, F., Hausherr, E., Dargent-Molina, P., Delmas, P. D., et al. (1998). How hip and whole-body bone mineral density predict hip fracture in elderly women: The EPIDOS prospective study. Osteoporosis International, 8, 247–254. Tuohy, K. M., Finlay, R. K., Wynne, A. G., & Gibson, G. R. (2001). A human volunteer study on the prebiotic effects of HP-inulin—Faecal bacteria enumerated using fluorescent in situ hybridization. Anaerobe, 7, 113–118. Tuohy, K. M., Kolida, S., Lustenberger, A. M., & Gibson, G. R. (2001). The prebiotic effects of biscuits containing partially hydrolyzed guar gum and fructo-oligosaccharides—A human volunteer study. British Journal of Nutrition, 86, 341–348. Van Loo, J. (2004). The specificity of the interaction with intestinal bacterial fermentation by prebiotics determines their physiological efficacy. Nutrition Research Reviews, 17, 89–98. Weaver, C. M. (2005). Inulin, oligofructose and bone health: Experimental approaches and mechanisms. British journal of Nutrition, 93, S99–S103. Zafar, T. A., Weaver, C. M., Zhao, Y., Martin, B. R., & Wastney, M. E. (2004). Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats. Journal of Nutrition, 134, 399–402.
International Dairy Journal 16 (2006) 1092–1097 www.elsevier.com/locate/idairyj
Review
Inulin and oligofructose as functional ingredients to improve bone mineralization D. Bosscher, J. Van Loo, A. Franck Orafti, Tiense Suikerraffinaderij, Aandorenstraat 1, 3300 Tienen, Belgium Received 4 May 2005; accepted 6 October 2005
Abstract Studies in animal models have shown increased calcium availability with inulin and oligofructose in the diet. This possibly beneficial effect of inulin-type fructans on the delay of osteoporosis was further evaluated in rats and it was found that accumulation of bone mineral and formation of improved trabecular network structure were indeed stimulated. In ovari-ectomized rats, oligofructose increased bone mineral content (BMC) and impeded ovari-ectomy induced loss of bone structure. These findings support the hypotheses that inulin and oligofructose might influence peak bone mass during adolescence in humans. Studies in girls with a high habitual calcium intake showed increased calcium absorption after supplementation of an oligofructose-enriched inulin (8 g d1) in the diet. This effect was highest in girls showing a habitual low degree of calcium absorption. Recently, a 1 y intervention trial on pre-pubertal girls and boys (n ¼ 100) found significantly increased calcium absorption in the group receiving oligofructose-enriched inulin (8 g d1) after 8 wks and the effect lasted during the whole intervention period, resulting in improved BMC and significantly increased bone mineral density compared to the controls. r 2006 Elsevier Ltd. All rights reserved. Keywords: Inulin; Oligofructose; Prebiotics; Calcium absorption; Bone mineralization
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effects on calcium absorption and bone mineralization in animals . . . . 2.1. Low, medium and high calcium diets . . . . . . . . . . . . . . . . . . . . 2.2. Combination of short and long-chain inulin-type fructans . . . . . 3. Effects on calcium absorption and bone mineralization in humans . . . . 3.1. Short-term studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Long-term studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Relevance of the data compared with current calcium strategies . 4. Effects on reduction of osteoporosis risk . . . . . . . . . . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
. . . . . . . . . . .
1092 1093 1093 1094 1094 1094 1095 1095 1096 1096 1097
1. Introduction
Corresponding author. Tel.: +32 16 801 268; fax: +32 16 801 359.
E-mail address: [email protected] (D. Bosscher). 0958-6946/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.idairyj.2005.10.028
Nutritional factors influence skeletal development during growth and bone maintenance during adulthood. Therefore, nutrition plays an important role in the pathophysiological process of osteoporosis. Osteoporosis is
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
acknowledged as one of the leading health care problems in the world and about one in three post-menopausal women and a substantial number of men above 50 will have an osteoporosis-related fracture at some point (Consensus Development Statement, 1997). Among nutrients with potential impact on bone health, most attention has been focused on calcium and bone mineral accrual. During childhood and adolescence adequate calcium intakes contribute to achieve peak bone mass between the ages of 20 and 25. After a decade or so in which bone mass remains more or less constant, loss of bone tissue and of calcium begins to occur and becomes significant as ageing processes. In particular, loss of bone in women accelerates in the years immediately after the menopause. The young woman’s skeleton has a bone mineral content (BMC) of about 2200 g, of which 32% or 708 g is elemental calcium (Ellis, Shypailo, Hergenroeder, Perez, & Abrams, 1996). This amount must be accumulated over the first 20 y of life at an average accretion rate of 35 g y1 or 97 mg d1 (Parfitt, 1994). This mean value obscures the considerable variability in rate of calcium uptake during growth of the skeleton, especially during adolescence. Pubertal growth spurt is associated with a rapid increase in calcium gain by the skeleton corresponding with higher rates of dietary calcium absorption and of kinetically determined bone calcium deposition in the bone than those in pre-puberty or adulthood. Abrams et al. (2000) found higher calcium absorption, bone calcium deposition rate (calcium gain) and markers of bone metabolism in the late pre-pubertal and the pubertal period (Tanner stage 2) (average calcium gain 110745 and 135753 mg d1, respectively). According to Martin, Bailey, McKay, and Whiting (1997) the highest rate of calcium gain is around 174 mg d1 for boys and 212 mg d1 for girls and lags about 1–1.5 y behind the age at which growth velocity reaches its peak at the age of 13.3 y for boys and 11.4 y for girls. In the study of Hui, Johnston, and Mazess (1985) peak rates of calcium accretion were about 160 mg d1 for girls (12 y old) and 200 mg d1 for boys (16 y of age). Calcium intake influences mineral accrual in growing children. However, optimal calcium uptakes in school-aged children are rarely attained (Alaimo, McDowel, & Briefel, 1994). This inadequate supply of calcium to the rapidly expanding skeletal volume might result into a suboptimal amount of bone mineral per unit of skeletal volume. Skeletal fragility is considered a major cause of the high incidence of forearm fractures in children near the age at which growth velocity reaches its maximum and the bones are growing at their fastest rate (Goulding et al., 1998; Goulding, Jones, Taylor, Manning, & Williams, 2000; Parfitt, 1994). This bone mineral deficit due to rapid skeletal growth might have also implications later in life, e.g. osteoporosis. Active ingredients such as inulin and oligofructose, are gaining more and more attention because they improve calcium absorption from the diet. High absorption of
1093
calcium from the diet increases peak bone mass and therefore might postpone the risk of osteoporosis-induced fractures at older age. In this perspective, inulin and oligofructose can play a relatively important role in the prevention of osteoporosis from infancy to the last decade of life. Inulin and oligofructose are prebiotic fibres obtained from the chicory root (Cichorium intybus) and are composed of b(2-1) linked fructose units, schematically given as GFn and Fn (G ¼ glucose, F ¼ fructose and n ¼ number of F-units). Native inulin encompasses a family of linear structures (GFn) varying in degree of polymerization (DP) from 3 to 60 (average DP ¼ 10). Oligofructose is obtained by partial hydrolysis of inulin and has a small DP ranging from 2 to 8 (average DP ¼ 4). Prebiotics are non-digestible food ingredients that are beneficial for the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can improve the host’s health (Gibson, Probert, Van Loo, Rastall, & Roberfroid, 2004). Inulin and oligofructose are not digested and reach the colon intact where they are fermented by the microflora, particularly by the endogenous lactic acid bacteria (LAB), bifidobacteria and lactobacilli (Gibson, Beatty, & Cummings, 1995; Kleessen, Sykura, Zunft, & Blaut, 1997; Langlands, Hopkins, Coleman, & Cummings, 2004; Menne, Guggenbuhl, & Roberfroid, 2000; Rao, 2001; Tuohy, Finlay, Wynne, & Gibson, 2001; Tuohy, Kolida, Lustenberger, & Gibson, 2001). The aim of this paper is to review current evidence on the effects of the prebiotics inulin and oligofructose on calcium absorption and bone metabolism and to provide state of the art information on the role of inulin and oligofructose in improving long-term bone health. Description of the mechanisms by which inulin and oligofructose influence calcium (and magnesium) absorption is given by Scholz-Ahrens and Schrezenmeir (2002) and by Weaver (2005). 2. Effects on calcium absorption and bone mineralization in animals 2.1. Low, medium and high calcium diets Over the past 10 y, experiments in animal models have repeatedly shown that inulin and oligofructose increase calcium absorption from the diet. First experiments performed in growing rats found a significant higher apparent calcium absorption after 25 days by addition of 10% native inulin or oligofructose to the diet compared with placebo (respectively, 40% or 43% vs. 25% apparent calcium retention) (Po0:05). The animals in this study were fed a standard diet with normal calcium levels (0.7%) (Delzenne, Aertssens, Verplaetse, Roccaro, & Roberfroid, 1995). This change in calcium absorption from diets supplemented with inulin-type fructans was further evaluated by determining the effect of three experimental diets (low,
ARTICLE IN PRESS 1094
D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
medium and high in calcium) on bone health in growing rats. Four weeks old rats were randomized into 9 different groups receiving 0% (control), 5% or 10% long-chain inulin with 0.2%, 0.5%, or 1% calcium in their respective diets. The trial lasted for 22 wks during which parameters of bone mineralization were measured at four different time points (10, 14, 18, 22 wks). From wk 10 to wk 22, in all three calcium groups fed the two levels of inulin (5% and 10%), changes in whole body BMC (WBBMC) (P ¼ 0:02) and in whole body bone mineral density (WBBMD) were significant as compared with those in the controls (Po0:001). Long-term inulin administration resulted in more accumulation of bone mineral and improved structure of the trabecular network in rats fed low, medium, or high calcium diets (Roberfroid, Cumps, & Devogelaer, 2002). Whether the improved calcium absorption seen with inulin-type fructans also led to the postponement or prevention of osteoporosis was further investigated in adult ovariectomised rats (animal model for post-menopausal women) fed with diets containing normal (0.5%) and high (1%) calcium levels. The semi-purified diets contained moreover either 10% or no (control) oligofructose . After 16 wks, bone calcium content in the femur was significantly increased in both oligofructose supplemented groups (normal and high calcium level in diet) as compared to both control groups (Po0:05). Calcium content in the lumbar vertebra was also increased in the oligofructose supplemented group fed with high calcium diet as compared to that in the corresponding control group (Po0:05). Moreover, the oligofructose supplementation of the diets impeded ovariectomy induced loss of bone (trabecular) structure in tibia irrespective of the calcium content of the diets (Scholz-Ahrens, Ac- il, & Schrezenmeir, 2002). 2.2. Combination of short and long-chain inulin-type fructans In a subsequent study it was aimed to investigate the effects of inulin-type fructans with different chain lengths and what the effect would be of a combination of both short and long-chain inulins. Adult rats were fed a normal calcium diet (0.5%) supplemented with 10% long-chain inulin, 10% oligofructose, or 10% of a blend of oligofructose and long-chain inulin (oligofructose-enriched inulin), or a non-supplemented diet (control). After 4 wks, calcium absorption improved in all fructan supplemented diets. Applying the oligofructose-enriched inulin did not only increase the apparent calcium absorption but also the calcium balance significantly. Values for calcium absorption were 58.177.4% and 47.975.5% of apparent absorption (Po0:05), whereas those for calcium balance were 58.578.2 and 46.876.3 mg d1 (Po0:05) in the oligofructose-enriched inulin group and the control group, respectively. It appeared that a synergistic effect was obtained by combining the short with the long-chain
inulin-type fructan fractions with respect to calcium absorption (Coudray, Tressol, Gueux, & Rayssiguier, 2003). Details on the composition of this synergistically active mixture of oligofructose and long-chain inulin (abbreviated as SYN1) are described by Van Loo (2004). The improved functionality of the SYN1 led to the setup of short-term studies to evaluate the effect of SYN1 on calcium kinetics in ovariectomised rats by catheterization of (jugular) veins after 45Ca administration (orally). Rats that were fed semi-purified diets containing only 5% of SYN1 during 21 d showed significantly increased calcium absorption (Po0:005), bone retention (Po0:005), femoral calcium content (Po0:05) and femoral BMD (Po0:05) compared to the control rats. Moreover, kinetic data on bone metabolism showed improved bone balance and suppression of bone turnover (Zafar, Weaver, Zhao, Martin, & Wastney, 2004). 3. Effects on calcium absorption and bone mineralization in humans 3.1. Short-term studies To evaluate the effect of SYN1 on calcium absorption during adolescence, human intervention trials were undertaken by measuring true calcium absorption using dual stable isotope analysis techniques (46Ca/42Ca) in urine collected during 48 h. Twenty-nine adolescent girls (11–13 y old) were randomized in a double-blind manner and their calcium status was followed for 2 times 3 wks (2 wks washout between treatments) in a crossover intervention study. Girls had calcium intakes of 1300–1500 mg d1 and were supplemented with 8 g d1 of SYN1 or with sucrose (placebo) added to calcium-fortified orange juice. True calcium absorption was significantly higher in the group receiving SYN1 (38.2%79.8%) than in the placebo treatment (32.3%79.8%) (P ¼ 0:01) (Griffin et al., 2002). It appeared that consumption of 8 g d1 of SYN1 added to the daily diet significantly improved calcium absorption in girls with normal habitual calcium intakes. However, to further evaluate the subject characteristics that are associated with this beneficial effect, an additional 25 newly recruited girls were enrolled in a second study. Globally, it was a two-center study (Houston, Texas and Omaha, Nebraska) with a total of 54 adolescent girls (av. 12.4 y old). Overall, the data confirmed the significant increase in calcium absorption observed earlier with SYN1 (36.179.8%) compared with the placebo (33.179.2%; P ¼ 0:027). The most consistent identifiable determinant of a beneficial effect of SYN1 on calcium absorption was the fractional calcium absorption during the placebo period, with those individuals with lower calcium absorption during the placebo period showing the greatest increase in calcium absorption in response to SYN1. This finding is important as these girls might be most likely to benefit from SYN1 supplementation to their daily diet (Griffin, Hicks, Heaney, & Abrams, 2003). Since the subjects
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
A long-term intervention trial was recently conducted to determine whether the increased true calcium absorption seen with SYN1 consumption resulted in an additional net mineral accretion in bone in pubertal girls and boys (Tanner stage 2 and 3), since calcium accretion is at its optimal stage during the pubertal ages and its level determines bone health at later age. Randomized girls were all pre-menarcheal since calcium retention tends to be maximal at this stage and lowers at post-menarcheal age (Jackman et al., 1997). About 100 girls and boys of 9–12 y old and with normal calcium intakes (900–1000 mg Ca d1) participated in the intervention study that lasted 1 y. They were randomized in a double-blind controlled manner to receive either 8 g d1 of SYN1 or maltodextrin (placebo) added to the diet in a calcium-fortified orange juice or milk. The findings are presented in Figs. 1–3. Subjects enrolled in the SYN1 group had significantly higher true calcium absorption, 38.5%71.2% compared with controls 30.071.3%, already after 8 wks of supplementation (Po0:001). The higher absorption percentage was kept during the whole intervention trial, 37.772.1% for the SYN1 group and 31.772.3% for controls (P ¼ 0:048), respectively. Correspondingly, SYN1 supplemented subjects had a significantly higher change in whole body BMC (WBBMC), 245711 g y1, than controls, 210710 g y1 (P ¼ 0:03). Under the assumption that the fraction of calcium per g BMC is 32%, these values correspond to daily skeletal calcium accretion of 218710 mg d1 for the SYN1 group and 189710 mg d1 for controls (P ¼ 0:04). This leads to a calculation of an additional net accretion of 30715 mg Ca d1. The change in WBBMD was also significantly greater with respect to the SYN1 supplemented subjects, 0.04770.004 g cm2 y1 compared with the controls, 0.03270.004 g cm2 y1 (P ¼ 0:01), with an increment in WBBMD after 1 y of 0.01570.004 g cm2 y1 (Z-score difference ¼ 0.1870.08, P ¼ 0:02) (Abrams et al., 2005). It appears that increased true calcium absorption with 8 g d1 of SYN1 during pubertal growth enhances bone mineralization probably resulting in increased peak bone mass during adolescence. 3.3. Relevance of the data compared with current calcium strategies One might consider what the relevance is of these findings compared with current dietary strategies to improve bone mass during adolescence. Much emphasis
**
* 38.0 True Ca absorption (%)
3.2. Long-term studies
40.0
36.0 34.0 32.0 30.0 oligofructose-enriched inulin
control
28.0 0
4
2
10
6 8 Time (months)
12
Fig. 1. True calcium availability (%) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructoseenriched inulin or maltodextrin (control) for 8 wks and 1 y. * Represent significant difference compared with the controls Po0:001. P ¼ 0:04. (Abrams et al., 2005)
350 300 Change in WBBMC (g y-1)
received very similar test meals, the cause of this variation does not result from the varying presence of enhancers or inhibitors of calcium absorption in the diets, but rather from the subjects’ tanner stages or genotypes of which some are likely to benefit more from SYN1 consumption than others.
1095
* 250 200 150 100 50 0 control
oligofructose-enriched inulin
Fig. 2. Change in whole body bone mineral content (WBBMC) (g y1) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructose-enriched inulin or maltodextrin (control) for 1 y (Abrams et al., 2005).
has been laid on the promotion of high calcium foods (e.g. dairy foods) or the use of calcium supplements to achieve optimal bone formation. Increased consumption of dairy products by pubertal girls with habitual low calcium intakes has indeed found to increase their BMC and bone mass accrual (Chan, Hoffman, & McMurry, 1995). The beneficial effects of supplement use during pubertal age are less clear. Studies in girls receiving calcium supplements on a daily basis during 1 y found only moderate effects on their BMD, without any improvements in the mineral content of the bones. These girls, however, were at menarcheal age and had habitual calcium intakes around recommended levels (Molgaard, Thomsen, & Michaelsen, 2004). Other studies in girls with normal and low calcium intakes and receiving supplements during a long term, did
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
1096 0.06 Change in WBBMD (g cm−2 y−1)
*
comparable to or exceeds that seen in trials of calcium supplementation alone (Molgaard et al., 2004),
0.05
4. Effects on reduction of osteoporosis risk 0.04 0.03 0.02 0.01 0.00 control
oligofructose-enriched inulin
Fig. 3. Change in whole body bone mineral density (WBBMD) (g cm2 y1) of the subjects (mean7standard error of the mean) after supplementation of the diets with oligofructose-enriched inulin or maltodextrin (control) for 1 y. *Represent significant difference compared with the controls P ¼ 0:01. (Abrams et al., 2005).
found significant effects on bone acquisition at various sites (indicated by increased BMD) (Lloyd et al., 1993; Dodiuk, Rozen, Rennert, Rennert, & Ish-Shalom, 2005; Matkovic et al., 2005). These studies again failed to demonstrate significant changes in BMC with calcium supplementation (Lloyd et al., 1993; Dodiuk et al., 2005). That adequate calcium intake during early adulthood not only has shortterm effects on bone mineralization, but also affects bone health during whole life, is demonstrated by the low skeletal bone-mineral density in adult women who reported low intake of milk in early adulthood compared with those women with medium or high intakes (New, Bolton-Smith, Grubb, & Reid, 1997). It appears that during the phase of rapid growth suboptimal calcium intake is one limiting factor for adequate bone mineralization throughout life. Therefore, strategies to increase the absorption of the ingested calcium may offer another approach to improve bone mineralization on the long term. As reviewed in this manuscript, several wellcontrolled studies in animals found significant higher calcium absorption with inulin, oligofructose or oligofructose-enriched inulin (SYN1) from low, medium or high calcium diets. Randomized human intervention trials (stable isotopes) demonstrated (on average) a 20% (significant) increase in calcium absorption following SYN1 administration to a normal calcium diet. Moreover, that this increased calcium absorption with SYN1 resulted into a higher calcium accretion, BMD and BMC (vs. the control subjects) was recently demonstrated (Abrams et al., 2005). This net benefit in calcium accretion into the skeleton with SYN1 was on average 11 g y1 during the stage pubertal growth. Although it is difficult to compare the data from this study with studies on calcium supplementation since most of these studies involve subjects with low calcium intakes or have different duration (Lloyd et al., 1993), it appears that this extra amount of calcium gain by the skeleton with SYN1 is
At present there are two approaches to prevent osteoporosis. The first is by optimizing bone mass acquisition in the skeleton during adolescent growth, the second is by minimizing bone loss in the post-menopausal period. Inulin and oligofructose might have a role in both. Increasing BMD and BMC with SYN1 could maximize peak bone mass during adolescence thereby reducing skeletal fragility at elder age. It appears that BMD at various sites is a good predictor of hip fractures (Cummings et al., 1993). A population-based cohort study in 7598 elderly women (75 y) found WBBMD to be a significant predictor of hip fracture (Schott et al., 1998). Indeed meta-analysis of prospective cohort studies found that bone density can predict fracture risk, which predictive ability was roughly similar or tended to be better than that of 1 standard deviation (SD) increases in blood pressure for stroke and better than that of 1 SD increases in serum cholesterol concentration for cardiovascular disease (Marshall, Johnell, & Wedel, 1996). Long observational studies are needed to reveal the protective effects of improved BMD during adolescence and the reduced risk of osteoporotic fractures at elder ages. Menopause is a time when estrogen deficiency leads to accelerated bone resorption and negative bone balance. Studies with SYN1 in rat models of the menopause showed increased bone balance and calcium absorption, whereas bone turn-over decreased in ovariectomised rats (Zafar et al., 2004). Other studies with oligofructose using the same rat model, showed that the increased calcium absorption rate following supplementation was translated into a greater calcium content of the femur and lumbar vertebrae. With respect to their bone architecture, oligofructose prevented ovariectomy-induced loss of bone structure (Scholz-Ahrens et al., 2002). These animal data show promising results on the role inulin and oligofructose can play in positively modulating bone mineral metabolism during post-menopausal age and need to be confirmed in human interventions trials which are currently ongoing. 5. Conclusion Consumption of inulin and oligofructose in humans, particularly SYN1, increases calcium absorption and improves both bone mineral content and bone mineral density (BMD) during periods of rapid growth. Rat models of the menopause suggest that increases in calcium absorption translate into a greater BMD following supplementation with inulin and oligofructose. A longterm study in adolescents indicated that substantial bone health benefits arose from SYN1 supplementation of 8 g d1. This has implications for future preventative strategies for osteoporosis.
ARTICLE IN PRESS D. Bosscher et al. / International Dairy Journal 16 (2006) 1092–1097
References Abrams, S. A., Copeland, K. C., Gunn, S. K., Gundberg, C. M., Klein, K. O., & Ellis, K. J. (2000). Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls. The Journal of Clinical Endocrinology & Metabolism, 85, 1805–1809. Abrams, S. A., Griffin, I. J., Hawthorne, K. M., Liang, L., Gunn, S. K., Darlington, G., & Ellis, K. J. (2005). A combination of prebiotic shortand long-chain fructans enhances calcium absorption and bone mineralization in young adolescents. American Journal of Clinical Nutrition, 82, 471–476. Alaimo, K., McDowel, M.A., & Briefel, R.R. (1994). Dietary intake of vitamins, minerals and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase I, 1988–1991. Advance Data from Vital and Health Statistics: No. 258. Hyattsville, MD, USA: National Center for Health Statistics. Chan, G. M., Hoffman, K., & McMurry, M. (1995). Effects of dairy products on bone and body composition in pubertal girls. Journal of Pediatrics, 126, 551–556. Consensus Development Statement. (1997). Who are candidates for prevention and treatment of osteoporosis? Osteoporosis International, 2, 285–289. Coudray, C., Tressol, J. C., Gueux, E., & Rayssiguier, Y. (2003). Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats. European Journal of Nutrition, 42, 91–98. Cummings, S. R., Black, D. M., Nevitt, M. C., Browner, W., Cauley, J., Ensrud, K., et al. (1993). Bone density at various sites for prediction of hip fractures. The Lancet, 341, 72–75. Delzenne, N., Aertssens, J., Verplaetse, H., Roccaro, M., & Roberfroid, M. (1995). Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy digestive balance in the rat. Life Sciences, 57, 1579–1587. Dodiuk, R. P., Rozen, G. S., Rennert, G., Rennert, H. S., & Ish-Shalom, S. (2005). Sustained effects of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake. American Journal of Clinical Nutrition, 81, 168–174. Ellis, K. J., Shypailo, R. J., Hergenroeder, A., Perez, M., & Abrams, S. (1996). Total body calcium and bone mineral content: comparison of dial-energy X-ray absorptiometry with neuron activation analysis. Journal of Bone Mineral Research, 11, 843–848. Gibson, G. R., Beatty, E. R., & Cummings, J. (1995). Selective fermentation of Bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology, 108, 975–982. Gibson, G. R., Probert, H. M., Van Loo, J., Rastall, R. A., & Roberfroid, M. B. (2004). Dietary modulation of the human colonic microbiota: Updating the concept of prebiotics. Nutrition Research Reviews, 17, 259–275. Goulding, A., Cannan, R., Williams, S. M., Gold, E. J., Taylor, R. W., & Lewis-Barned, N. J. (1998). Bone mineral density in girls with forearm fractures. Journal of Bone and Mineral Research, 13, 143–148. Goulding, A., Jones, I. E., Taylor, R. W., Manning, P. J., & Williams, S. M. (2000). More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. Journal of Bone and Mineral Research, 15, 2011–2018. Griffin, I. J., Davila, P. M., & Abrams, S. A. (2002). Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes. British Journal of Nutrition, 87, S187–S191. Griffin, I. J., Hicks, P. M. D., Heaney, R. P., & Abrams, S. A. (2003). Enriched chicory inulin increases calcium absorption mainly in girls with lower calcium absorption. Nutrition Research, 23, 901–909. Hui, S. L., Johnston, C. C., & Mazess, R. B. (1985). Bone mass in normal children and young adults. Growth, 49, 34–43. Jackman, L. A., Millane, S. S., Martin, B. R., Wood, O. B., McCabe, G. P., Peacock, M., et al. (1997). Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females. American Journal of Clinical Nutrition, 66, 327–333.
1097
Kleessen, B., Sykura, B., Zunft, H-J., & Blaut, M. (1997). Effects of inulin and lactose on fecal microflora, microbial activity and bowel habit in elderly constipated persons. American Journal of Clinical Nutrition, 65, 1397–1402. Langlands, S. J., Hopkins, M. J., Coleman, N., & Cummings, J. H. (2004). Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut, 53, 1610–1616. Lloyd, T., Andon, M. B., Rollings, N., Martel, J. K., Landis, J. R., Demers, L. M., et al. (1993). Calcium supplementation and bone mineral density in adolescent girls. The Journal of the Amercian Medical Association, 270, 841–844. Menne, E., Guggenbuhl, N., & Roberfroid, M. (2000). Fn-type chicory inulin hydrolysate has a prebiotic effect in humans. Journal of Nutrition, 130, 1197–1199. Martin, A. D., Bailey, D. A., McKay, H. A., & Whiting, S. (1997). Bone mineral and calcium accretion during puberty. American Journal of Clinical Nutrition, 66, 611–615. Marshall, D., Johnell, O., & Wedel, H. (1996). Meta-analysis of how well measures of one mineral density predict occurrence of osteoporotic fractures. British Medical Journal, 312, 1254–1259. Matkovic, V., Goel, P. K., Badenho-Stevens, N. E., Landoll, J. D., Li, B., Ilich, J. Z., et al. (2005). Calcium supplementation and bone mineral density in females from childhood adulthood: A randomised controlled trail. American Journal of Clinical Nutrition, 81, 175–188. Molgaard, C., Thomsen, B. L., & Michaelsen, K. F. (2004). Effect of habitual dietary calcium intake on calcium supplementation on 12–14y-old girls. American Journal of Clinical Nutrition, 80, 1422–1427. New, S. A., Bolton-Smith, C., Grubb, D. A., & Reid, D. M. (1997). Nutritional influences on bone mineral density: A cross-sectional study in premenopausal women. Amercian Journal of Clinical Nutrition, 65, 1831–1939. Parfitt, A. M. (1994). The two faces of growth: Benefits and risks to bone integrity. Osteoporosis International, 4, 382–398. Rao, V. A. (2001). The prebiotic properties of oligofructose at low intake levels. Nutrition Research, 21, 843–848. Roberfroid, M. B., Cumps, J., & Devogelaer, J. P. (2002). Dietary chicory inulin increases whole-body bone mineral density in growing male rats. Journal of Nutrition, 132, 3599–3602. Scholz-Ahrens, K. E., Ac- il, Y., & Schrezenmeir, J. (2002). Effect of oligofructose or dietary calcium on repeated calcium and phosphorus balances, bone mineralization and trabecular structure in ovariectomized rats. British Journal of Nutrition, 88, 365–377. Scholz-Ahrens, K. E., & Schrezenmeir, J. (2002). Inulin, oligofructose and mineral metabolism—experimental data and mechanism. British Journal of Nutrition, 87, S179–S186. Schott, A. M., Cormier, C. C., Favier, F., Hausherr, E., Dargent-Molina, P., Delmas, P. D., et al. (1998). How hip and whole-body bone mineral density predict hip fracture in elderly women: The EPIDOS prospective study. Osteoporosis International, 8, 247–254. Tuohy, K. M., Finlay, R. K., Wynne, A. G., & Gibson, G. R. (2001). A human volunteer study on the prebiotic effects of HP-inulin—Faecal bacteria enumerated using fluorescent in situ hybridization. Anaerobe, 7, 113–118. Tuohy, K. M., Kolida, S., Lustenberger, A. M., & Gibson, G. R. (2001). The prebiotic effects of biscuits containing partially hydrolyzed guar gum and fructo-oligosaccharides—A human volunteer study. British Journal of Nutrition, 86, 341–348. Van Loo, J. (2004). The specificity of the interaction with intestinal bacterial fermentation by prebiotics determines their physiological efficacy. Nutrition Research Reviews, 17, 89–98. Weaver, C. M. (2005). Inulin, oligofructose and bone health: Experimental approaches and mechanisms. British journal of Nutrition, 93, S99–S103. Zafar, T. A., Weaver, C. M., Zhao, Y., Martin, B. R., & Wastney, M. E. (2004). Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats. Journal of Nutrition, 134, 399–402.