Category Archives: Minerals

Review: Protein + Calcium May Benefit Bones – April 2011

Abstract

Dietary protein and bone health: harmonizing conflicting theories.

A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables.

Thorpe MP, Evans EM
Nutr. Rev. Apr 2011
PMID: 21457266

Review: Protein Recommended Intake – 2008

Abstract

Amount and type of protein influences bone health.

Many factors influence bone mass. Protein has been identified as being both detrimental and beneficial to bone health, depending on a variety of factors, including the level of protein in the diet, the protein source, calcium intake, weight loss, and the acid/base balance of the diet. This review aims to briefly describe these factors and their relation to bone health. Loss of bone mass (osteopenia) and loss of muscle mass (sarcopenia) that occur with age are closely related. Factors that affect muscle anabolism, including protein intake, also affect bone mass. Changes in bone mass, muscle mass, and strength track together over the life span. Bone health is a multifactorial musculoskeletal issue. Calcium and protein intake interact constructively to affect bone health. Intakes of both calcium and protein must be adequate to fully realize the benefit of each nutrient on bone. Optimal protein intake for bone health is likely higher than current recommended intakes, particularly in the elderly. Concerns about dietary protein increasing urinary calcium appear to be offset by increases in absorption. Likewise, concerns about the impact of protein on acid production appear to be minor compared with the alkalinizing effects of fruits and vegetables. Perhaps more concern should be focused on increasing fruit and vegetable intake rather than reducing protein sources. The issue for public health professionals is whether recommended protein intakes should be increased, given the prevalence of osteoporosis and sarcopenia.

Heaney RP, Layman DK
Am. J. Clin. Nutr. May 2008
PMID: 18469289 | Free Full Text

Protein Increases Calcium Absorption and Retention From a Low-Calcium Diet – 2009

Abstract

Dietary protein and calcium interact to influence calcium retention: a controlled feeding study.

The effect of meat protein on calcium retention at different calcium intakes is unresolved. The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium.In a randomized controlled feeding study with a 2 x 2 factorial crossover design, healthy postmenopausal women (n = 27) consumed either approximately 675 or approximately 1510 mg Ca/d, with both low and high protein (providing 10% and 20% energy) for 7 wk each, separated by a 3-wk washout period. After 3 wk, the entire diet was extrinsically labeled with (47)Ca, and isotope retention was monitored by whole-body scintillation counting. Clinical markers of calcium and bone metabolism were measured.
High compared with low dietary protein significantly increased calcium retention from the low-calcium (29.5% compared with 26.0% absorbed) but not the high-calcium diet (18% absorbed). For the low-calcium diet, this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion. Protein-related calciuretic effects were independent of dietary calcium. Testing at 1, 2, 3, 5, and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion. High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase, or tartrate-resistant acid phosphatase.
In healthy postmenopausal women, a moderate increase in dietary protein, from 10% to 20% of energy, slightly improved calcium absorption from a low-calcium diet, nearly compensating for a slight increase in urinary calcium excretion. Under practical dietary conditions, increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health.

Hunt JR, Johnson LK, Fariba Roughead ZK
Am. J. Clin. Nutr. May 2009
PMID: 19279077 | Free Full Text

Review: Protein – March 2003

Abstract

Protein and bone health: literature review and counselling implications.

For decades, public health promotion campaigns on bone health have emphasized the importance of adequate calcium and vitamin D intakes, as well as weight-bearing physical activity. However, no obvious consensus has emerged on the role of dietary protein. To identify what agreement does exist in the literature, in this article we review the theoretical basis for protein’s role in bone health, assess some recent cross-sectional and prospective studies, and generate recommendations for practice. There is general agreement in the literature that higher protein intake increases urinary calcium loss; the body compensates for this loss by increasing calcium absorption in the gut, providing that calcium intake is sufficient. A possible explanation for calcium loss, the “acid-ash” hypothesis, is discussed, and suggestions are made about food choices that may counter the calciuric effect of protein. A survey of cross-sectional and prospective studies shows equivocal results, with confounding variables complicating the analysis. Both deficient and excessive protein intakes have been shown to affect bone health negatively, although lower and upper thresholds have not been determined. Practical advice on achieving bone health is given, with an emphasis on the use of Canada’s Food Guide to Healthy Eating in setting dietary goals.

Cloutier GR, Barr SI
Can J Diet Pract Res 2003
PMID: 12631403

Review: Protein + Calcium – March 2003

Abstract

Interaction of dietary calcium and protein in bone health in humans.

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

Dawson-Hughes B
J. Nutr. Mar 2003
PMID: 12612168 | Free Full Text

Isoflavones + Calcium Better Than Isoflavones or Calcium in Ovariectomized Rats

Abstract

Isoflavones with supplemental calcium provide greater protection against the loss of bone mass and strength after ovariectomy compared to isoflavones alone.

Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract + high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n = 10) or ovx (n = 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE + Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P < 0.05) among sham and IE groups and greatest (P < 0.05) among the OVX group. Final body weight was lowest (P < 0.05) among shams and highest (P < 0.05) among the OVX group while IE + Ca were lighter (P < 0.05) than all ovx groups. Femur and vertebra BMD was greater (P < 0.05) among IE + Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P < 0.05) among IE + Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P < 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE + Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.

Breitman PL, Fonseca D, Cheung AM, Ward WE
Bone Oct 2003
PMID: 14555264

Also, it’s interesting that Calcium alone was superior to Isoflavones alone.

MSM Enhances Osteoblasts and GH Signaling In Vitro

Abstract

MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.

Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH) is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway, thereby regulating expression of genes including insulin-like growth factor (IGF)-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R). In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs). MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2) were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b.

Joung YH, Lim EJ, Darvin P, Chung SC…
PLoS ONE 2012
PMID: 23071812 | Free Full Text

Chromium Could Have Bone Benefits

Abstract

Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density.

Activation of osteoclasts by parathyroid hormone (PTH) is mediated by PTH stimulation of osteoblasts, and is dependent on a PTH-induced rise in protein kinase C activity. Physiological levels of insulin reduce the ability of PTH to activate protein kinase C in osteoblasts, suggesting that insulin may be a physiological antagonist of bone resorption. In addition, insulin is known to promote collagen production by osteoblasts. These findings imply that efficient insulin activity may exert an anabolic effect on bone, and rationalize the many clinical studies demonstrating reduced bone density in Type I diabetes. Recently, the insulin-sensitizing nutrient chromium picolinate has been found to reduce urinary excretion of hydroxyproline and calcium in postmenopausal women, presumably indicative of a reduced rate of bone resorption. This nutrient also raised serum levels of dehydroepiandrosterone-sulfate, which may play a physiological role in the preservation of postmenopausal bone density. The impact of chromium picolinate (alone or in conjunction with calcium and other micronutrients) on bone metabolism and bone density, merits further evaluation in controlled studies.

McCarty MF
Med. Hypotheses Sep 1995
PMID: 8569546

Vitamin D3 + K2 + Sr + Mg + DHA as Effective as Bisphosphonates in Women

Abstract

Combination of Micronutrients for Bone (COMB) Study: bone density after micronutrient intervention.

Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micronutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micronutrient therapy with a combination that included vitamin D(3), vitamin K(2), strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals where bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.

Genuis SJ, Bouchard TP
J Environ Public Health 2012
PMID: 22291722 | Free Full Text

Vitamin C + Calcium is Associated with Increased Bone Mass in Postmenopausal Women

Abstract

The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study.

Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0. 017 g/cm2 increment in BMD (P = 0.002 femoral neck; P = 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P = 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and </=500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm2 in BMD per 100 mg vitamin C (P = 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the beta coefficient in the higher calcium stratum was similar to that for the total sample (beta = 0.0172, P = 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (beta = 0.0199, P = 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg.

Hall SL, Greendale GA
Calcif. Tissue Int. Sep 1998
PMID: 9701620