Category Archives: Sodium

High Sodium Causes Loss of Calcium in Rats


Calcium metabolism and bone calcium content in normal and oophorectomized rats consuming various levels of saline for 12 months.

The effect of different intakes of salt for 12 mo on bone calcium content and urinary excretion of calcium and hydroxyproline were examined in sham operated and oophorectomized (OX) rats to determine the long term effects of high sodium intake and its interaction with estrogen deficiency. Sham operated (n = 24) and OX (n = 24) rats were divided into groups of six rats in a 2 x 4 design. One group of sham and one of OX rats were given 0, 2, 6 or 18 g/L sodium chloride to drink. Urine samples were collected at 0, 2, 4, 6, 10 and 12 mo for the measurement of sodium, calcium, creatinine and hydroxyproline. At the end of 12 mo, blood was taken for measurement of calcium, albumin, alkaline phosphatase and creatinine and the left femur was removed and analyzed for calcium and phosphate. Body weights of the OX rats were higher than the sham operated controls. At the start of the experiment (10 d after OX) urinary excretions of calcium and hydroxyproline were significantly higher in OX rats. However, after 4-6 mo, they were significantly lower in OX rats. Calcium excretion and hydroxyproline excretion were increased by high salt intake, and there was a significant correlation between sodium and calcium excretion (r = 0.962). Bone calcium content of OX rats was lower than their corresponding sham-operated controls. Sodium intake also had a significant effect on bone calcium content. Multiple regression analysis showed that OX and sodium intake explained 7.6% and 1.5% of the variation in bone calcium content. We conclude that high sodium intake causes increased loss of calcium and reduces bone calcium content in sham-operated as well as OX rats.

Chan EL, Swaminathan R
J. Nutr. Mar 1998
PMID: 9482774 | Free Full Text

Lowering Sodium Increases the Effect of Calcium to Reduce Bone Loss in 124 Postmenopausal Women


A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women.

The influence of urinary sodium excretion and dietary calcium intake was examined in a 2-y longitudinal study of bone density in 124 women postmenopausal for > 10 y. Analysis of bone density changes showed that urinary sodium excretion was negatively correlated with changes in bone density at the intertrochanteric and total hip sites. Multiple-regression analysis of dietary calcium intake and urine sodium excretion on the change in bone density showed that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass over 2 y at the hip and ankle sites. These data suggest that an effect of reducing bone loss equivalent to that achieved by a daily dietary increase of 891 mg (22 mmol) Ca can also be achieved by halving daily sodium excretion. No bone loss occurred at the total hip site at a calcium intake of 1768 mg/d (44 mmol/d) or a urine sodium excretion of 2110 mg/d (92 mmol/d). We report a significant effect of sodium excretion on bone loss in this population.

Devine A, Criddle RA, Dick IM, Kerr DA…
Am. J. Clin. Nutr. Oct 1995
PMID: 7572702 | Free Full Text

Fish Oil Benefits Bone in Salt-Loaded Rats


Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible role of kidney.

There is evidence that dietary fats are important components contributing in bone health and that bone mineral density is inversely related to sodium intake. Salt loading is also known to impose negative effects on renal function. The present study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on bone changes imposed by salt loading, highlighting the role of kidney as a potential mechanism involved in this effect. Male Wistar rats were divided into three groups: control group, salt-loaded group consuming 2% NaCl solution as drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1 g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium, potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP), creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth factor-beta1 (TGF-β1) were measured. The right tibia and kidney were removed for histologic examination and renal immunohistochemical analysis for endothelial nitric oxide synthase (eNOS) was performed. The results revealed that omega-3 reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine, urea, and TGF-β1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3 as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness, decreased osteoclast number, and increased newly formed osteoid bone. Renal morphology was found preserved. In conclusion, omega-3 prevents the disturbed bone status imposed by salt loading. This osteoprotective effect is possibly mediated by attenuation of alterations in Ca(2+), Pi, and ALP, and improvement of renal function and arterial blood pressure.

Ahmed MA, Abd El Samad AA
Physiol Rep Oct 2013
PMID: 24303178 | Free Full Text

The acquisition and maintenance of bone mass and strength are influenced by environmental factors, including physical activity and nutrition (Massey and Whiting 1996). Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis (Massey and Whiting 1996). Evidence indicates that dietary fats can influence bone health (Tartibian et al. 2010), in particular the omega-3 (n-3) polyunsaturated fatty acids (PUFAs), as they have been shown to inhibit osteoclast activity and enhance osteoblast activity (Watkins et al. 2003). Eicosapentaenoic acid (EPA) supplementation was found to increase bone mineral density in postmenopausal women (Terano 2001). Beneficial effects of n-3 PUFAs on markers of bone resorption and formation in animal (Shen et al. 2006) and human (Griel et al. 2007) studies have, also, been observed.

On the other hand, a number of studies suggested a detrimental effect of dietary salt on bone. Devine et al. (1995) showed that change in bone mineral density was inversely related to sodium intake and that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass. High-sodium diet was found to increase urinary calcium excretion and cause loss of bone calcium (Chan and Swaminathan 1998), while reducing sodium intake complemented the beneficial skeletal effects of the Dietary Approaches to Stop Hypertension diet (Lin et al. 2003). Furthermore, an epidemiological study of men and women has shown that salt intake is associated with markers of bone resorption and appears likely to be a risk factor for osteoporosis (Jones et al. 1997). Similar effect of sodium loading has been demonstrated in animal model (Gold and Gouldin 1995).


Review: Acid-Producing Diets May be Protective When Calcium is High


The acid-ash hypothesis revisited: a reassessment of the impact of dietary acidity on bone.

The acid-ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid-ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.

Nicoll R, McLaren Howard J
J. Bone Miner. Metab. Feb 2014
PMID: 24557632

Sodium Associated with Lower Bone Density in Young Women


Higher urinary sodium, a proxy for intake, is associated with increased calcium excretion and lower hip bone density in healthy young women with lower calcium intakes.

We assessed 24-h urinary sodium (Na) and its relationship with urinary calcium (Ca) and areal bone mineral density (aBMD) at the whole body, lumbar spine and total hip in a cross-sectional study. 102 healthy non-obese women completed timed 24-h urine collections which were analyzed for Na and Ca. Dietary intakes were estimated using a validated food frequency questionnaire. Participants were grouped as those with lower vs. higher calcium intake by median split (506 mg/1000 kcal). Dietary Na intake correlated with 24-h urinary loss. Urinary Na correlated positively with urinary Ca for all participants (r = 0.29, p < 0.01) and among those with lower (r = 0.37, p < 0.01) but not higher calcium intakes (r = 0.19, p = 0.19). Urinary Na was inversely associated with hip aBMD for all participants (r = -0.21, p = 0.04) and among women with lower (r = -0.36, p < 0.01) but not higher (r = -0.05, p = 0.71) calcium intakes. Urinary Na also entered a regression equation for hip aBMD in women with lower Ca intakes, contributing 5.9% to explained variance. In conclusion, 24-h urinary Na (a proxy for intake) is associated with higher urinary Ca loss in young women and may affect aBMD, particularly in those with lower calcium intakes.

Bedford JL, Barr SI
Nutrients Nov 2011
PMID: 22254088 | Free Full Text

The potential implications of sodium-induced calciuria for bone are likely to be more serious in those with low calcium intakes, who may be unable to increase calcium absorption to fully compensate for increased urinary losses. For example, Heaney [3] noted that to offset the average urinary calcium loss of 1 mmol (40 mg) associated with an increased sodium intake of 100 mmol (2300 mg), gross calcium absorption efficiency would need to increase to 34% (from 25%) in those with intakes of 600 mg/day, and to about 50% (from 37%) in those with intakes of 300 mg/day-and that this may not be possible. However, at intakes of 1200 mg/day, absorption efficiency would only need to increase from to 23% (from 20%) [3]. Empirical support for the idea that high calcium intakes may protect against high sodium intakes is provided by the study of Ilich et al. [20]. In a 3-year prospective study, postmenopausal women were randomly assigned to maintain usual sodium intake of about 3000 mg/day or to reduce intake to 1500 mg/day. All women also received calcium supplements, and total calcium intake averaged over 1300 mg/day. Because compliance with the sodium intervention was not high, results were reported by tertile of observed urinary sodium excretion rather than by initial group assignment. No negative associations between urinary sodium and bone density were observed [20]. This suggests that, at least in postmenopausal women with high calcium intakes, sodium intake does not adversely affect bone.

Higher Sodium + Adequate Calcium is Not Detrimental for Bone in Women


Higher habitual sodium intake is not detrimental for bones in older women with adequate calcium intake.

Based on the calciuric effect of sodium (Na), it has been speculated, although not proven, that higher Na intake might have a detrimental effect on bone health. The objective was to determine the relationship between Na intake (expressed as urinary Na) and bone mineral density/content (BMD/BMC) during a 3-year study. Participants were healthy, postmenopausal, Caucasian women (n = 136 at baseline) with no medications affecting bone. After baseline screening, half were instructed to reduce sodium intake to approximately 1,500 mg/day (intervention). The other half remained on habitual intake of approximately 3,000 mg/day (control). All subjects were given calcium and vitamin D supplements to achieve recommended levels. Anthropometries, densitometry, blood and 24-h urine analyses, and dietary and activity records were assessed every 6 months. Data were analyzed as a continuum, irrespective of the initial assignment to a control or intervention group, using random effects regressions with repeated measures analysis of variance to examine changes over time. Results showed that subjects with higher Na intake had higher BMD in the forearm and spine at baseline and all subsequent time-points (p < 0.01). In the forearm, time and higher urinary calcium modified results, producing a curvilinear decrease in BMD (p < 0.01). In the spine, more active individuals had higher BMD at all time-points. We conclude that higher sodium intake, within the range consumed, had a positive effect on some skeletal sites and no adverse effect on bone in women who had adequate calcium and vitamin D intake.

Ilich JZ, Brownbill RA, Coster DC
Eur. J. Appl. Physiol. Jul 2010
PMID: 20217116

Review: No Harm From Prevailing Sodium Intakes with Adequate Calcium


Role of dietary sodium in osteoporosis.

Sodium, in the form of sodium chloride, elevates urinary calcium excretion and, at prevailing calcium intakes, evokes compensatory responses that may lead to increased bone remodeling and bone loss. The calciuria is partly due to salt-induced volume expansion, with an increase in GFR, and partly to competition between sodium and calcium ions in the renal tubule. Potassium intakes in the range of current recommendations actually reduce or prevent sodium chloride-induced calciuria. At calcium intakes at or above currently recommended levels, there appear to be no deleterious effects of prevailing salt intakes on bone or the calcium economy, mainly because adaptive increases in calcium absorption offset the increased urinary loss. Such compensation is likely to be incomplete at low calcium intakes. Limited evidence suggests equivalent bone-sparing effects of either salt restriction or augmented calcium intakes. Given the relative difficulty of the former, and the ancillary benefits of the latter, it would seem that the optimal strategy to protect the skeleton is to ensure adequate calcium and potassium intakes.

Heaney RP
J Am Coll Nutr Jun 2006
PMID: 16772639

Low Sodium may be Risk Factor for Maintaining Calcium and Magnesium


Positive correlation between dietary intake of sodium and balances of calcium and magnesium in young Japanese adults–low sodium intake is a risk factor for loss of calcium and magnesium–.

The content of calcium (Ca) and magnesium (Mg) in sweat during exercise is considerably higher during a relatively low intake of sodium (Na) of 100 mmol/d than with an intake of 170 mmol/d. For this reason and also because Ca and Mg have a negative balance with a Na intake of 100 mmol/d, we analyzed the relationship between Na intake and balances of Ca and Mg in data from 11 balance studies. From 1986 to 2000, 109 volunteers (23 males, 86 females) with an age range of 18 to 28 y took part in mineral balance studies. The balance periods ranged from 5 to 12 d. In a given experiment, the diet of each subject contained the same quantity of food, although this varied between experiments, and was supplied during the balance period without consideration of body weight. In the data of all the studies (n= 109), the balances of Ca and Mg did not correlate positively with Na intake. However, when the data of the highest Na study were excluded, the balances of Ca and Mg correlated positively with Na intake. The mean value for the regression equation between Na intake and Ca and Mg balances when the respective balance was equal to zero were, 63.308 mg Na/kg BW/d (Ca: n=96, r2=0.134) and 60.977 mg Na/kg BW/d (Mg: n=96, r2=0.268), respectively. These values are considerably higher than Na requirements estimated by inevitable Na loss. Low dietary Na may therefore be a risk factor for maintaining positive balances of Ca and Mg.

Nishimuta M, Kodama N, Morikuni E, Yoshioka YH…
J. Nutr. Sci. Vitaminol. Aug 2005
PMID: 16261999

High Sodium has an Insignificant Effect on Bone Density in Rats


Sodium and calcium intakes and bone mass in rats revisited.

High sodium intake accompanied by insufficient dietary calcium may have detrimental effects on bone mass. Our study evaluated the effects of increased sodium and decreased calcium intakes on bone mineral density (BMD) and bone mineral content (BMC) in rats.
Four-month-old female Wistar rats were given deionized water or 1.8% solution of sodium chloride in deionized water and fed normal (1.2%) or marginal (0.33%) calcium in the diet for 2 mo. At the end of the experiment, BMD and BMC of the whole body and urinary sodium and calcium excretion were evaluated. All rats were killed and right femurs were removed to assess dry and ash weights. Two-way analysis of variance was used to evaluate effect of salt intake and effect of dietary calcium on these parameters.
Salt-loaded animals had greater water consumption during the entire 2-mo period and significantly lower body weight from week 5 of the experiment. High salt intake increased urine volume and urinary excretion of sodium and calcium. Urinary calcium was about five times higher in salt-loaded animals than in rats on deionized water irrespective of dietary calcium content. Calcium in diet itself had no significant effect on these parameters. High salt intake slightly, but not significantly, decreased BMD, BMC, and femur weights. Lower calcium in diet significantly decreased BMD, and its effect on femur ash weight almost reached a level of significance.
We confirmed the benefit of adequate calcium intake to BMD. Under our experimental condition, high salt intake in rats for 2 mo had no statistically significant effect on femur weights, BMD, or BMC even with marginal calcium in the diet.

Sarić M, Piasek M, Blanusa M, Kostial K…
Nutrition May 2005
PMID: 15850968

DASH Diet and Sodium Reduction Improve Bone in Adults


The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults.

Dietary strategies to prevent and treat osteoporosis focus on increased intake of calcium and vitamin D. Modification of whole dietary patterns and sodium reduction may also be effective. We examined the effects of two dietary patterns and three sodium levels on bone and calcium metabolism in a randomized feeding study. A total of 186 adults, aged 23-76 y, participated. After a 2-wk run-in period, participants were assigned randomly to diets containing three levels of sodium (50, 100 and 150 mmol/d) to be consumed for 30 d in random order. Serum osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), fasting serum parathyroid hormone (PTH), urinary sodium, potassium, calcium and cAMP were measured at baseline and at the end of each sodium period. The Dietary Approaches to Stop Hypertension (DASH) diet reduced serum OC by 8-11% and CTX by 16-18% (both P < 0.001). Urinary calcium excretion did not differ between subjects that consumed the DASH and control diets. Reducing sodium from the high to the low level significantly decreased serum OC 0.6 microg/L in subjects that consumed the DASH diet, fasting serum PTH 2.66 ng/L in control subjects and urinary calcium 0.5 mmol/24 h in both groups. There were no consistent effects of the diets or sodium levels on urinary cAMP. In conclusion, the DASH diet significantly reduced bone turnover, which if sustained may improve bone mineral status. A reduced sodium intake reduced calcium excretion in both diet groups and serum OC in the DASH group. The DASH diet and reduced sodium intake may have complementary, beneficial effects on bone health.

Lin PH, Ginty F, Appel LJ, Aickin M…
J. Nutr. Oct 2003
PMID: 14519796 | Free Full Text