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Potassium Citrate Increases Calcium Levels in Adults

Abstract

Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women.

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects’ dietary acid was completely neutralized (-11.3 mmol/d on 60 mmol/d; -29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (-46 ± 15.9 mg/d) and 90 mmol/d (-59 ± 31.6 mg/d) compared with placebo (p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus -80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance (p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (-34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; -71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed.

Moseley KF, Weaver CM, Appel L, Sebastian A…
J. Bone Miner. Res. Mar 2013
PMID: 22991267

Potassium Citrate Increases Bone Density and Volume in Adults

Abstract

Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial.

The acid load imposed by a modern diet may play an important role in the pathophysiology of osteoporosis. Our objective was to evaluate the skeletal efficacy and safety and the effect on fracture prediction of K-citrate to neutralize diet-induced acid loads.
We conducted a randomized, double-blind, placebo-controlled trial at a teaching hospital.
Subjects included 201 elderly (>65 yr old) healthy men and women (t-score of -0.6 at lumbar spine).
Intervention was 60 mEq of K-citrate daily or placebo by mouth. All subjects received calcium and vitamin D.
The primary outcome was change in areal bone mineral density (aBMD) at the lumbar spine by dual-energy x-ray absorptiometry after 24 months. Secondary endpoints included changes in volumetric density and microarchitectural parameters by high-resolution peripheral quantitative computed tomography in both radii and both tibiae and fracture risk assessment by FRAX (Switzerland).
K-citrate increased aBMD at lumbar spine from baseline by 1.7 ± 1.5% [95% confidence interval (CI) = 1.0-2.3, P < 0.001] net of placebo after 24 months. High-resolution peripheral quantitative computed tomography-measured trabecular densities increased at nondominant tibia (1.3 ± 1.3%, CI = 0.7-1.9, P < 0.001) and nondominant radius (2.0 ± 2.0%, CI = 1.4-2.7, P < 0.001). At nondominant radius, trabecular bone volume/tissue volume increased by 0.9 ± 0.8%, (CI = 0.1-1.7), trabecular thickness by 1.5 ± 1.6% (CI = 0.7-2.3), and trabecular number by 1.9 ± 1.8% (CI = 0.7-3.1, for all, P < 0.05). K-citrate diminished fracture prediction score by FRAX significantly in both sexes.
Among a group of healthy elderly persons without osteoporosis, treatment with K-citrate for 24 months resulted in a significant increase in aBMD and volumetric BMD at several sites tested, while also improving bone microarchitecture. Based on the effect on fracture prediction, an effect on future fractures by K-citrate is possible.

Jehle S, Hulter HN, Krapf R
J. Clin. Endocrinol. Metab. Jan 2013
PMID: 23162100

Despite the conflicting evidence for the acid load theory, potassium or citrate nonetheless appear to increase bone density. How it does that is debated.

Potassium Citrate Reduces Resorption in Postmenopausal Women

Abstract

Effects of potassium citrate supplementation on bone metabolism.

Western diets rich in animal protein result in long-term acid loading that, despite corresponding increases in net renal acid excretion, may induce a chronic state of acidemia. This may have deleterious effects on both the kidney and bone, by increasing the risk of calcium stone in the former and leading to chemical dissolution of mineral alkaline salts in the latter. Whereas supplementation with alkaline citrate has been shown to reduce stone recurrences, its effect on bone turnover has received less attention. The aim of the present study was to evaluate whether potassium citrate favorably affects bone turnover markers in postmenopausal females with low bone density. Thirty women, aged 58 +/- 8.1 years, were enrolled and studied on basal conditions and after a 3-month course of potassium citrate supplementation (0.08-0.1 g/kg b.w. daily). Twenty-two women concluded the study while 8 withdrew. Twenty-four age-matched healthy women were taken as control cases. All were evaluated for electrolyte and acid-base balance-related parameters, bone turnover, markers and renal function. A significant decrease in net acid excretion was observed upon citrate supplementation, and this was paralleled by a significant decrease of urinary deoxypyridinolines, hydroxyproline-to-creatinine ratios, and, to a lesser extent, serum osteocalcin. Percent variations of urine citrate were inversely related to those of deoxypyridinolines and hydroxyproline. No change in these chemistries occurred in the control group. Our results suggest that treatment with an alkaline salt, such as potassium citrate, can reduce bone resorption thereby contrasting the potential adverse effects caused by chronic acidemia of protein-rich diets.

Marangella M, Di Stefano M, Casalis S, Berutti S…
Calcif. Tissue Int. Apr 2004
PMID: 15255069

Bicarbonate, but Not Potassium, Decreases Resorption

Abstract

Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women.

Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies.
The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and women. Design, Participants, and Intervention: In this double-blind, controlled trial, 171 men and women age 50 and older were randomized to receive placebo or 67.5 mmol/d of potassium bicarbonate, sodium bicarbonate, or potassium chloride for 3 months. All subjects received calcium (600 mg of calcium as triphosphate) and 525 IU of vitamin D(3) daily.
Twenty-four-hour urinary N-telopeptide and calcium were measured at entry and after 3 months. Changes in these measures were compared across treatment groups in the 162 participants included in the analyses.
Bicarbonate affected the study outcomes, whereas potassium did not; the two bicarbonate groups and the two no bicarbonate groups were therefore combined. Subjects taking bicarbonate had significant reductions in urinary N-telopeptide and calcium excretion, when compared with subjects taking no bicarbonate (both before and after adjustment for baseline laboratory value, sex, and changes in urinary sodium and potassium; P = 0.001 for both, adjusted). Potassium supplementation did not significantly affect N-telopeptide or calcium excretion.
Bicarbonate, but not potassium, had a favorable effect on bone resorption and calcium excretion. This suggests that increasing the alkali content of the diet may attenuate bone loss in healthy older adults.

Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C…
J. Clin. Endocrinol. Metab. Jan 2009
PMID: 18940881 | Free Full Text

Supplementation with potassium did not significantly alter calcium excretion or markers of bone turnover in this study. This is in contrast to earlier reports of Lemann et al. (19) and Jones et al. (20) who found that increasing potassium intake decreased urinary calcium excretion. The apparently conflicting observation that higher potassium intake is associated with higher BMD in healthy perimenopausal women (21) may result from the fact that potassium-rich diets tend to be alkali-producing, in that they are rich in fruits and vegetables. Treatment with potassium did enhance sodium excretion, as has been documented widely.

In conclusion, we have found that reducing the acidogenicity of the diet into the alkali-producing range with bicarbonate lowers calcium excretion and the bone resorption rate in healthy older men and women consuming rather typical acid-producing American diets. Treatment with 67.5 mmol/d of potassium bicarbonate was safe and well tolerated in this population. Increasing intake of alkali merits further consideration as a safe and low-cost approach to improving skeletal health in older men and women.

Review: Potassium and Osteoporosis

Abstract

Potassium and health.

Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints.

Weaver CM
Adv Nutr May 2013
PMID: 23674806 | Free Full Text

The full text includes several pages about osteoporosis. This is just the final summary at the end of that section:

In summary, benefits of potassium on bone are seen typically when given as organic salts at relatively high doses of 60 to 90 mmol/d (2400–3600 mg/d). Organic salts of potassium reduce urinary calcium loss and improve calcium balance at these levels. But whether that is related to protection against skeletal buffering of an acidogenic diet is still a topic for debate. Perhaps acid-base balance is not the mechanism in healthy kidneys, but as kidney function declined with age, it may be an important mechanism. The glomerular filtration rate declines by as much as 50% from age 20 to 80 y (68), or perhaps excess acid only affects bone through interaction with receptors on bone cells to stimulate bone turnover, and this process is reduced by the alkaline organic salts of potassium.

 

Policosanol Prevents Bone Loss in Ovariectomized Rats

Abstract

Policosanol prevents bone loss in ovariectomized rats.

Osteoporosis is characterized by reduced bone mass, abnormal bone architecture and increased fracture risk. Ovariectomy impairs bone mass and metabolism in rats and ovariectomized rats are considered as a suitable model of postmenopausal osteoporosis. Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. The purpose of this study was to determine whether policosanol could prevent bone loss in the bones of ovariectomized rats by comparing its effects with those induced by estradiol. Sprague Dawley female rats were randomly distributed in four groups: a sham-operated group treated with Tween/H2O vehicle and three groups of ovariectomized rats treated with 17beta-estradiol (30 microg/kg/day) or policosanol (50 and 200 mg/kg/day), respectively, for 3 months. At treatment completion the rats were sacrificed, their bones removed and variables of bone resorption and formation were investigated by histomorphometry. Ovariectomy increased trabecular separation but diminished the number and thickness of trabecules. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number of osteoclasts and their surface area induced by ovariectomy. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. In conclusion, policosanol prevented bone loss and decreased bone resorption in ovariectomized rats, suggesting that it should be potentially useful in preventing bone loss in postmenopausal women.

Noa M, Más R, Mendoza S, Gámez R…
Drugs Exp Clin Res 2004
PMID: 15366788

Cumin Increases Bone Density and Strength in Ovariectomized Rats – Possible SERM

Abstract

Methanolic extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in rats.

Several animal and clinical studies have shown that phytoestrogens, plant-derived estrogenic compounds, can be useful in treating postmenopausal osteoporosis. Phytoestrogens and phytoestrogen-containing plants are currently under active investigation for their role in estrogen-related disorders. The present study deals with anti-osteoporotic evaluation of phytoestrogen-rich plant Cuminum cyminum, commonly known as cumin. Adult Sprague-Dawley rats were bilaterally ovariectomized (OVX) and randomly assigned to 3 groups (10 rats/group). Additional 10 animals were sham operated. OVX and sham control groups were orally administered with vehicle while the other two OVX groups were administered 0.15 mg/kg estradiol and 1 g/kg of methanolic extract of Cuminum cyminum fruits (MCC) in two divided doses for 10 weeks. At the end of the study blood, bones and uteri of the animals were collected. Serum was evaluated for calcium, phosphorus, alkaline phosphatase and tartarate resistant acid phosphatase. Bone density, ash density, mineral content and mechanical strength of bones were evaluated. Scanning electron microscopic (SEM) analysis of bones (tibia) was performed. Results were analyzed using ANOVA and Tukeys multiple comparison test. MCC (1 g/kg, p.o.) significantly reduced urinary calcium excretion and significantly increased calcium content and mechanical strength of bones in comparison to OVX control. It showed greater bone and ash densities and improved microarchitecture of bones in SEM analysis. Unlike estradiol it did not affect body weight gain and weight of atrophic uterus in OVX animals. MCC prevented ovariectomy-induced bone loss in rats with no anabolic effect on atrophic uterus. The osteoprotective effect was comparable with estradiol.

Shirke SS, Jadhav SR, Jagtap AG
Exp. Biol. Med. (Maywood) Nov 2008
PMID: 18824723

Sodium Associated with Lower Bone Density in Young Women

Abstract

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

Abstract

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

Abstract

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