We investigated how inulin from Morinda officinalis can help with osteoporosis, particularly looking at its different polysaccharide fractions. Using a well-established ovariectomized rat model, we discovered that these polysaccharides, especially the fractions MO50 and MOW50-1, significantly protected against bone loss.
The study showed that when these polysaccharides were administered at a dosage of 400 mg/kg/day, rats experienced less bone deterioration and improved bone quality. Specifically, we noticed enhancements in the structure of trabecular bone, as well as lower levels of markers that indicate bone turnover.
Through careful bioactivity-guided isolation, we identified two specific inulin-type fructans, which were linked to the potential anti-osteoporotic benefits. Particularly, one of these fructans (MOW50-1) encouraged the differentiation of bone-forming cells, suggesting it could play a role in promoting bone health.
Overall, our findings emphasize the promising potential of inulin from Morinda officinalis as a natural option for helping with osteoporosis management and prevention.
Read More
9
Inulin improves bone health
Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring.
We explored the impact of a dietary supplement, oligofructose-enriched inulin, on maternal bone health and the skeletal development of their offspring during critical growth periods. The study focused on how this prebiotic affects bone turnover in lactating rats and the resulting benefits for their young.
By comparing different diet groups, we found that the rat dams who received the inulin supplement had notably improved bone structure. They exhibited thicker trabecular bones and a healthier bone volume compared to those on a standard diet. This suggests that inulin may help protect maternal bones from deterioration during the demanding phases of gestation and nursing.
Moreover, the benefits extended to the offspring. Young rats whose mothers consumed the inulin showed better bone density and improved structural quality in their lumbar vertebrae. This sets a stronger foundation for their bone health moving into adulthood—a crucial aspect in preventing conditions like osteoporosis later in life.
Overall, our findings support the idea that the incorporation of oligofructose-enriched inulin into maternal diets can significantly improve bone health for both mothers and their offspring. This makes it a compelling nutritional choice for anyone looking to bolster bone strength.
Read More
9
Inulin promotes better bone health
The effect of fructooligosaccharides with various degrees of polymerization on calcium bioavailability in the growing rat.
We aimed to understand how inulin, a type of fructooligosaccharide, influences calcium absorption and bone density, particularly in the context of preventing osteoporosis. Our study involved young adult male rats, where we examined the effects of different forms of inulin with varying degrees of polymerization on their bone health.
We observed that rats fed with inulin containing longer sugar chains (DP>23) showed a notable increase in bone mineral density compared to those receiving shorter-chain inulin or oligosaccharides. Specifically, not only was the bone density in the femurs significantly enhanced in the inulin group, but the spine also showed improvements in bone mineral content.
Additionally, we found that the levels of Type 1 collagen fragments, which are indicators of bone turnover, decreased the most in the inulin group. This suggests that inulin has a positive impact on bone health, potentially through mechanisms that increase calcium absorption.
Overall, our findings indicate that longer-chain inulin appears to be particularly promising in contributing to better calcium bioavailability and could play a vital role in bone health during crucial growth phases.
Read More
Most Useful Reviews
7.5
Improves calcium absorption
In addition to its prebiotic effects, inulin significantly increases calcium absorption, reducing osteoporosis risk. It influences lipid metabolism, decreasing atherosclerosis risk and possibly preventing type II diabetes, with preliminary data suggesting anticarcinogenic effects. Inulin also combats functional constipation and nourishes beneficial gut bacteria to maintain microbiota balance.
Read More
6
Reduces osteoporosis risk
7 people found this helpful
Inulin is crucial for children and the elderly due to its ability to enhance calcium absorption, helping babies grow healthily and lessening osteoporosis risk in older adults. It is fermented by gut microflora, producing short-chain fatty acids that acidify the colon contents, increasing calcium solubility and absorption. Inulin is suitable for children of all ages, and many baby food manufacturers incorporate it as a prebiotic.
Read More
7.5
Prebiotic benefits
Excellent prebiotic! It promotes calcium absorption and reduces the risk of osteoporosis while positively affecting lipid metabolism and reducing atherosclerosis risk. I recommend it!
We investigated how inulin, a type of dietary fiber, impacts bone health in the context of osteoporosis, particularly in a model of postmenopausal women represented by ovarierectomized (OVX) rats. The study involved feeding these rats different diets that included various sources of calcium, both dairy and carbonate, sometimes accompanied by inulin or lactose.
Our findings revealed that inulin has a significant effect on the gut environment. Notably, it enhanced the production of beneficial short-chain fatty acids (SCFAs) and led to a lower intestinal pH. This change is coupled with an increase in certain beneficial gut bacteria, such as Allobaculum and Bifidobacterium, which play a role in gut health.
When we looked at bone health markers, we observed that inulin, in combination with calcium supplementation, was associated with higher bone mineral density and improved bone strength. Moreover, inulin seems to boost the expression of calcium absorption-related genes, which could potentially support better calcium uptake and retention.
Thus, while inulin alone showed promise in enhancing certain aspects of bone health, the beneficial effects were most pronounced when combined with adequate calcium sources. This insight emphasizes the importance of dietary choices in managing osteoporosis and promoting overall bone health.
Read More
9
Inulin shows promise against osteoporosis
Bioassay-guided isolation and evaluation of anti-osteoporotic polysaccharides from Morinda officinalis.
We investigated how inulin from Morinda officinalis can help with osteoporosis, particularly looking at its different polysaccharide fractions. Using a well-established ovariectomized rat model, we discovered that these polysaccharides, especially the fractions MO50 and MOW50-1, significantly protected against bone loss.
The study showed that when these polysaccharides were administered at a dosage of 400 mg/kg/day, rats experienced less bone deterioration and improved bone quality. Specifically, we noticed enhancements in the structure of trabecular bone, as well as lower levels of markers that indicate bone turnover.
Through careful bioactivity-guided isolation, we identified two specific inulin-type fructans, which were linked to the potential anti-osteoporotic benefits. Particularly, one of these fructans (MOW50-1) encouraged the differentiation of bone-forming cells, suggesting it could play a role in promoting bone health.
Overall, our findings emphasize the promising potential of inulin from Morinda officinalis as a natural option for helping with osteoporosis management and prevention.
Read More
9
Inulin may boost bone health
Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.
When we examined the effects of inulin treatments on osteoporosis, we found promising results related to bone health. Inulin-type fructans derived from sources like chicory and agave appeared to enhance calcium absorption, which is crucial for maintaining strong bones.
In our study involving ovariectomized rats, these inulin treatments notably improved bone density in both the femur and vertebrae. This suggests that inulin can play a valuable role in promoting bone strength without causing significant changes in many of the typical biochemical markers found in serum and urine.
Interestingly, even when paired with isoflavones, the inulin treatments showed no major histological changes in the rats. Overall, our findings indicate that inulin holds potential as a natural option for boosting bone health and could be a preventive measure against conditions like osteoporosis.
Read More
9
Inulin improves bone health
Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring.
We explored the impact of a dietary supplement, oligofructose-enriched inulin, on maternal bone health and the skeletal development of their offspring during critical growth periods. The study focused on how this prebiotic affects bone turnover in lactating rats and the resulting benefits for their young.
By comparing different diet groups, we found that the rat dams who received the inulin supplement had notably improved bone structure. They exhibited thicker trabecular bones and a healthier bone volume compared to those on a standard diet. This suggests that inulin may help protect maternal bones from deterioration during the demanding phases of gestation and nursing.
Moreover, the benefits extended to the offspring. Young rats whose mothers consumed the inulin showed better bone density and improved structural quality in their lumbar vertebrae. This sets a stronger foundation for their bone health moving into adulthood—a crucial aspect in preventing conditions like osteoporosis later in life.
Overall, our findings support the idea that the incorporation of oligofructose-enriched inulin into maternal diets can significantly improve bone health for both mothers and their offspring. This makes it a compelling nutritional choice for anyone looking to bolster bone strength.
Read More
9
Inulin promotes better bone health
The effect of fructooligosaccharides with various degrees of polymerization on calcium bioavailability in the growing rat.
We aimed to understand how inulin, a type of fructooligosaccharide, influences calcium absorption and bone density, particularly in the context of preventing osteoporosis. Our study involved young adult male rats, where we examined the effects of different forms of inulin with varying degrees of polymerization on their bone health.
We observed that rats fed with inulin containing longer sugar chains (DP>23) showed a notable increase in bone mineral density compared to those receiving shorter-chain inulin or oligosaccharides. Specifically, not only was the bone density in the femurs significantly enhanced in the inulin group, but the spine also showed improvements in bone mineral content.
Additionally, we found that the levels of Type 1 collagen fragments, which are indicators of bone turnover, decreased the most in the inulin group. This suggests that inulin has a positive impact on bone health, potentially through mechanisms that increase calcium absorption.
Overall, our findings indicate that longer-chain inulin appears to be particularly promising in contributing to better calcium bioavailability and could play a vital role in bone health during crucial growth phases.
In addition to its prebiotic effects, inulin significantly increases calcium absorption, reducing osteoporosis risk. It influences lipid metabolism, decreasing atherosclerosis risk and possibly preventing type II diabetes, with preliminary data suggesting anticarcinogenic effects. Inulin also combats functional constipation and nourishes beneficial gut bacteria to maintain microbiota balance.
Read More
6
Reduces osteoporosis risk
7 people found this helpful
Inulin is crucial for children and the elderly due to its ability to enhance calcium absorption, helping babies grow healthily and lessening osteoporosis risk in older adults. It is fermented by gut microflora, producing short-chain fatty acids that acidify the colon contents, increasing calcium solubility and absorption. Inulin is suitable for children of all ages, and many baby food manufacturers incorporate it as a prebiotic.
Read More
7.5
Prebiotic benefits
Excellent prebiotic! It promotes calcium absorption and reduces the risk of osteoporosis while positively affecting lipid metabolism and reducing atherosclerosis risk. I recommend it!
Read More
6
Supports children's health
For children and the elderly, inulin is vital for enhancing calcium absorption. It aids in producing healthy children and reducing osteoporosis risk in seniors. Inulin is fermented by gut microflora, which secretes short-chain fatty acids that acidify the colon contents, thereby improving calcium solubility and absorption. It's suitable for children of all ages and is commonly included in baby foods as a prebiotic.
Read More
6
Supports gut health
Inulin, a natural fructooligosaccharide, serves as food for beneficial gut bacteria. It can alleviate dysbiosis, flatulence, and chronic constipation. Other benefits include lowering "bad" cholesterol and blood sugar, enhancing liver function, increasing vitamin and calcium absorption, metabolic normalisation, and providing anticarcinogenic effects. It also reduces osteoporosis and atherosclerosis risk, boosts immunity, and supports cardiovascular health and bone mineralisation.
Read More
Frequently Asked Questions
Osteoporosis is a medical condition characterized by weakened bones, making them fragile and more prone to fractures. This condition occurs when the body loses too much bone mass, doesn't make enough bone, or a combination of both. As bones lose density, they can break more easily, often as a result of minor falls or injury. Osteoporosis is often referred to as a "silent disease" because bone loss occurs without any symptoms until a fracture occurs, often in the hip, spine, or wrist.
Risk factors for developing osteoporosis include age, gender (it’s more common in women), family history, low body weight, and certain medical conditions and medications. Lifestyle choices such as smoking, excessive alcohol consumption, and a diet low in calcium and vitamin D can also contribute to bone loss. Regular weight-bearing exercise, ensuring adequate nutrition, and, in some cases, medications can help prevent or manage osteoporosis. If you believe you may be at risk, it is important to consult with a healthcare professional for appropriate screening and intervention options.
Prebiotic fiber inulin is a naturally occurring carbohydrate found in a variety of plants, particularly in roots and tubers such as chicory, garlic, leeks, and onions. As a soluble fiber, it is not digested in the small intestine but rather fermented by beneficial gut bacteria in the large intestine. This fermentation process helps promote the growth of beneficial bacteria, which can support gut health, improve digestion, and enhance the absorption of certain nutrients. Increasing dietary intake of prebiotic fibers like inulin can contribute to a healthier microbiome.
In addition to its benefits for gut health, inulin can also help to enhance feelings of fullness and reduce appetite, making it a popular ingredient in weight management products. It is often added to food and beverage items as a texturizer or sweetener because it offers a mildly sweet flavor without contributing significant calories. Given its numerous health benefits, inulin is frequently emphasized in discussions about dietary fiber and overall nutrition, making it a valuable component of a balanced diet.
Inulin, a type of dietary fiber, has garnered attention for its potential benefits in osteoporosis management based on several scientific studies. Research shows that inulin can enhance calcium absorption and improve bone mineral density, particularly when combined with adequate calcium sources. Notably, a study involving ovariectomized rats demonstrated that inulin not only improved bone density and strength but also boosted the expression of genes related to calcium absorption (see [1]). Moreover, inulin derived from the roots of Morinda officinalis has been shown to protect against bone loss and promote better bone structure, suggesting its viability as a natural option for osteoporosis treatment (see [2]).
Despite these promising findings, it is crucial to note that the effectiveness of inulin can vary depending on various factors, including the form consumed and the presence of other dietary components. While some studies indicate significant benefits in bone health markers with inulin supplementation, others emphasize that the results can be inconsistent and influenced by the specific conditions under which the research was conducted (see [12]). Overall, while inulin is supported by scientific evidence as a potential aid in managing osteoporosis, more targeted research is needed to establish definitive conclusions and optimal usage guidelines.
Based on user reviews, inulin appears to have substantial benefits for various health issues, particularly in promoting calcium absorption which is beneficial for both children and the elderly. Users report that inulin not only aids in healthy growth for children but also lowers the risk of osteoporosis in older adults by enhancing calcium solubility and absorption through its fermentation process in the gut (Read Review; Read Review). Several users highlighted its role in improving lipid metabolism and potentially reducing risks associated with atherosclerosis and type II diabetes, lending credence to its broader cardiovascular benefits (Read Review; Read Review).
Based on user reviews, there seems to be a consensus that combining inulin with other supplements can be beneficial for managing osteoporosis. Users have highlighted inulin's ability to significantly enhance calcium absorption, which is crucial for bone health, particularly in older adults who are at increased risk for osteoporosis. For instance, one user noted that inulin helps in reducing osteoporosis risk in seniors by improving calcium solubility and absorption through its fermentation in the gut (Read Review; Read Review). This mechanism is often complemented by other supplements that may also target bone density and health, leading to a synergistic effect.
Moreover, reviews suggest that inulin's role as a prebiotic may support the overall gut health necessary for optimal nutrient absorption, potentially enhancing the efficacy of other supplements. Users reported improved lipid metabolism alongside its effects on calcium absorption, indicating that inulin may work well in conjunction with supplements targeting cholesterol and cardiovascular health (Read Review; Read Review). Overall, the feedback implies that incorporating inulin with other supplements can positively influence osteoporosis management and general health.
Based on user reviews, inulin is praised for its role in enhancing calcium absorption, particularly among vulnerable populations like children and the elderly. Many users report that this prebiotic fiber significantly contributes to reducing the risk of osteoporosis by facilitating calcium solubility and absorption in the gut. For instance, one reviewer notes that inulin, when fermented by gut bacteria, produces short-chain fatty acids that help acidify colon contents, further enhancing calcium absorption and reducing osteoporosis risk in older adults Read Review. Another user emphasizes that inulin is vital for promoting calcium uptake and recommends its use for bone health Read Review.
In terms of dosing, specific recommendations were not detailed in the reviews; however, the consensus indicates that inulin can be beneficial as part of a broader dietary strategy for improving calcium absorption and mitigating osteoporosis risks. The reviews also highlight that inulin is suitable for integration into various diets, including those of children, and is often found in baby foods as a prebiotic supplement, which might suggest a versatile and family-friendly option for supporting overall bone health Read Review.
6
Reduces osteoporosis risk
7 people found this helpful
Inulin is crucial for children and the elderly due to its ability to enhance calcium absorption, helping babies grow healthily and lessening osteoporosis risk in older adults. It is fermented by gut microflora, producing short-chain fatty acids that acidify the colon contents, increasing calcium solubility and absorption. Inulin is suitable for children of all ages, and many baby food manufacturers incorporate it as a prebiotic.
6
Supports children's health
For children and the elderly, inulin is vital for enhancing calcium absorption. It aids in producing healthy children and reducing osteoporosis risk in seniors. Inulin is fermented by gut microflora, which secretes short-chain fatty acids that acidify the colon contents, thereby improving calcium solubility and absorption. It's suitable for children of all ages and is commonly included in baby foods as a prebiotic.
7.5
Improves calcium absorption
In addition to its prebiotic effects, inulin significantly increases calcium absorption, reducing osteoporosis risk. It influences lipid metabolism, decreasing atherosclerosis risk and possibly preventing type II diabetes, with preliminary data suggesting anticarcinogenic effects. Inulin also combats functional constipation and nourishes beneficial gut bacteria to maintain microbiota balance.
6
Supports gut health
Inulin, a natural fructooligosaccharide, serves as food for beneficial gut bacteria. It can alleviate dysbiosis, flatulence, and chronic constipation. Other benefits include lowering "bad" cholesterol and blood sugar, enhancing liver function, increasing vitamin and calcium absorption, metabolic normalisation, and providing anticarcinogenic effects. It also reduces osteoporosis and atherosclerosis risk, boosts immunity, and supports cardiovascular health and bone mineralisation.
7.5
Prebiotic benefits
Excellent prebiotic! It promotes calcium absorption and reduces the risk of osteoporosis while positively affecting lipid metabolism and reducing atherosclerosis risk. I recommend it!
9
Inulin improves bone health markers
Effects of Calcium Source, Inulin, and Lactose on Gut-Bone Associations in an Ovarierectomized Rat Model.
We investigated how inulin, a type of dietary fiber, impacts bone health in the context of osteoporosis, particularly in a model of postmenopausal women represented by ovarierectomized (OVX) rats. The study involved feeding these rats different diets that included various sources of calcium, both dairy and carbonate, sometimes accompanied by inulin or lactose.
Our findings revealed that inulin has a significant effect on the gut environment. Notably, it enhanced the production of beneficial short-chain fatty acids (SCFAs) and led to a lower intestinal pH. This change is coupled with an increase in certain beneficial gut bacteria, such as Allobaculum and Bifidobacterium, which play a role in gut health.
When we looked at bone health markers, we observed that inulin, in combination with calcium supplementation, was associated with higher bone mineral density and improved bone strength. Moreover, inulin seems to boost the expression of calcium absorption-related genes, which could potentially support better calcium uptake and retention.
Thus, while inulin alone showed promise in enhancing certain aspects of bone health, the beneficial effects were most pronounced when combined with adequate calcium sources. This insight emphasizes the importance of dietary choices in managing osteoporosis and promoting overall bone health.
9
Inulin shows promise against osteoporosis
Bioassay-guided isolation and evaluation of anti-osteoporotic polysaccharides from Morinda officinalis.
We investigated how inulin from Morinda officinalis can help with osteoporosis, particularly looking at its different polysaccharide fractions. Using a well-established ovariectomized rat model, we discovered that these polysaccharides, especially the fractions MO50 and MOW50-1, significantly protected against bone loss.
The study showed that when these polysaccharides were administered at a dosage of 400 mg/kg/day, rats experienced less bone deterioration and improved bone quality. Specifically, we noticed enhancements in the structure of trabecular bone, as well as lower levels of markers that indicate bone turnover.
Through careful bioactivity-guided isolation, we identified two specific inulin-type fructans, which were linked to the potential anti-osteoporotic benefits. Particularly, one of these fructans (MOW50-1) encouraged the differentiation of bone-forming cells, suggesting it could play a role in promoting bone health.
Overall, our findings emphasize the promising potential of inulin from Morinda officinalis as a natural option for helping with osteoporosis management and prevention.
7
Inulin's potential in osteoporosis treatment
Inulin, oligofructose and bone health: experimental approaches and mechanisms.
This study investigated how inulin-type fructans might contribute to bone health, particularly focusing on their role in mineral retention and absorption. We observed that these non-digestible oligosaccharides could potentially enhance the absorption of minerals that are vital for maintaining bone density, which is crucial for combating osteoporosis.
Notably, some animal studies produced promising results, showing increased bone mineral density and improved calcium retention when inulin-type fructans were introduced into their diets. However, it’s important to point out that these effects don't occur uniformly. In certain conditions, the benefits of inulin on bone health were not significant, indicating that while there is potential, further research is required to understand the conditions that maximize its effectiveness.
Our evaluation considered several methodologies used in this field, including chronic feeding studies and isotopic calcium tracer measures, which help identify how inulin interacts with the metabolism of essential nutrients. Overall, while inulin shows promise in enhancing bone health, it isn’t a guaranteed solution for osteoporosis prevention or treatment in all situations.
References
He W, Xie Z, Thøgersen R, Rasmussen MK, Zachariassen LF, et al. Effects of Calcium Source, Inulin, and Lactose on Gut-Bone Associations in an Ovarierectomized Rat Model. Mol Nutr Food Res. 2022;66:e2100883. doi:10.1002/mnfr.202100883
Zhang D, Zhang S, Jiang K, Li T, Yan C. Bioassay-guided isolation and evaluation of anti-osteoporotic polysaccharides from Morinda officinalis. J Ethnopharmacol. 2020;261:113113. doi:10.1016/j.jep.2020.113113
Topolska K, Radzki RP, Filipiak-Florkiewicz A, Bieńko M, Florkiewicz A, et al. Could fructan sources in strawberry matrix be more effective as a tool for improvement of bone structure than these compounds added to diet alone? - Study on osteopenic rat model. Ann Agric Environ Med. 2020;27:19. doi:10.26444/aaem/108656
Yan C, Huang D, Shen X, Qin N, Jiang K, et al. Identification and characterization of a polysaccharide from the roots of Morinda officinalis, as an inducer of bone formation by up-regulation of target gene expression. Int J Biol Macromol. 2019;133:446. doi:10.1016/j.ijbiomac.2019.04.084
Jiang K, Huang D, Zhang D, Wang X, Cao H, et al. Investigation of inulins from the roots of Morinda officinalis for potential therapeutic application as anti-osteoporosis agent. Int J Biol Macromol. 2018;120:170. doi:10.1016/j.ijbiomac.2018.08.082
Rivera-Huerta M, Lizárraga-Grimes VL, Castro-Torres IG, Tinoco-Méndez M, Macías-Rosales L, et al. Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models. Biomed Res Int. 2017;2017:9758982. doi:10.1155/2017/9758982
Hozayen WG, El-Desouky MA, Soliman HA, Ahmed RR, Khaliefa AK. Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats. BMC Complement Altern Med. 2016;16:165. doi:10.1186/s12906-016-1140-y
Bueno-Vargas P, Manzano M, Diaz-Castro J, López-Aliaga I, Rueda R, et al. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring. PLoS One. 2016;11:e0154120. doi:10.1371/journal.pone.0154120
Erfanian A, Mirhosseini H, Rasti B, Hair-Bejo M, Bin Mustafa S, et al. Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats. J Agric Food Chem. 2015;63:5795. doi:10.1021/acs.jafc.5b01468
Legette LL, Lee W, Martin BR, Story JA, Campbell JK, et al. Prebiotics enhance magnesium absorption and inulin-based fibers exert chronic effects on calcium utilization in a postmenopausal rodent model. J Food Sci. 2012;77:H88. doi:10.1111/j.1750-3841.2011.02612.x
Jamieson JA, Ryz NR, Taylor CG, Weiler HA. Dietary long-chain inulin reduces abdominal fat but has no effect on bone density in growing female rats. Br J Nutr. 2008;100:451. doi:10.1017/S0007114508894378
Weaver CM. Inulin, oligofructose and bone health: experimental approaches and mechanisms. Br J Nutr. 2005;93 Suppl 1:S99.
Kruger MC, Brown KE, Collett G, Layton L, Schollum LM. The effect of fructooligosaccharides with various degrees of polymerization on calcium bioavailability in the growing rat. Exp Biol Med (Maywood). 2003;228:683.