Metagenics
Calcitite Protect
Highly absorbable form of calcium
Microcrystalline hydroxyapatite, a superior bioavailable form of calcium, with phosphorous and bioactive growth factors to support and enhance skeletal development.
- Supports bone mineralisation and the development of bone mass
- Supports healthy gestation and pregnancy outcomes
- Supports post-menopausal bone health
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BENEFITS
CLINICALLY PROVEN;
Superior efficacy and tolerability over calcium carbonate
Promotes the development of peak bone mass
Supports the maintenance of bone mineral density
Stimulates osteoblast differentiation and proliferation, enhancing skeletal development
Promoting messenger ribonucleic acid (mRNA) osteoblastic cell expression, enhancing skeletal development
Enhances bone matrix formation
Mitigate the rate of bone loss, and reduces the risk of bone fracture after menopause
Mitigates bone losses associated with corticosteroids
Prevention of Franctures, Osteopenia / Osteoporosis
Maintains endothelial vascular function to expand the capacity of blood flow through the placenta
Reduces the risk of maternal pre-eclampsia
Reduces the risk of pre-term birth
Recommended Calcium Daily Intake
1 - 3 years: 500 mg/d
4 - 6 years: 600 mg/d
7 - 18 years: 1,300 mg/d
19 - 50 years: 1,000 mg/d
50+ years: 1,000 – 1,300 mg/d
Pregnancy: 1,200 mg/d
Lactation: 1,000 mg/d
Low calcium intakes are a significant public health problem, with 56% of Australian adults failing to meet recommended daily intakes.[80]
SUPPORTS BONE MINERALISATION AND BONE MASS
Calcium accrual in the skeleton occurs at a steady rate during childhood, with bone mass peaking in early adulthood (Figure 2).[40] As such, ensuring that individuals meet calcium requirements during this developmental stage has the potential to increase BMD and enhance this process.[41] This, in turn, can modulate the rate of bone loss associated with a below-normal BMD that occurs with ageing.[42]
Adequate calcium consumption supports bone strength by building its mass within skeletal microarchitecture as well as facilitating micro-repair mechanisms that maintain the structural integrity of bones.[43],[44]
To develop bone mass, the body requires a combination of calcium and nutritional cofactors to enable osteoblasts to form bone matrix. Calcium in the form of whole bone extract, MCHC, consists of bone-growth enhancing proteins (including ossein, osteocalcin, type 1 collagen, type I and II insulin growth factor [IGF-1 and IGF-2], and transforming growth factor-beta {TGF-β}), which promote the formation of organic bone matrix.[46],[47]
MCHC also contains a blend of bone-building minerals including calcium, phosphorous, magnesium, potassium and zinc.[48],[49] Based on its unique properties and composition, MCHC mediates bone growth more effectively than conventional calcium supplements, such as calcium carbonate and calcium citrate.[50] Mechanisms attributed to MCHC’s bone-building effects include:
Significantly increasing procollagen type I carboxy-terminal propeptide (PICP),[51] a downstream matrix-building protein produced by osteoblasts that forms 90% of bone matrix[52];
Bone growth-factors, osteocalcin and collagen type I within MCHC, which stimulate osteoblast differentiation and proliferation.[53]
As a result, MCHC intake can enhance skeletal development during early adulthood and preserve BMD across the lifespan, as well as supporting adequate calcium intake. Boron also contributes to bone mineralisation by promoting messenger ribonucleic acid (mRNA) osteoblastic cell expression, thereby accelerating osteoblast activity[54],[55]; complimenting the effects of MCHC.
Furthermore, vitamin K1 (phylloquinone) plays a key role in many physiological processes including supporting bone mineralisation via the stimulation of gamma-carboxylation enzymes. These, in turn, activate vitamin K-dependant proteins, osteocalcin and matrix Gla (MGP), involved in bone matrix synthesis (Figure 3).[56]
In addition, vitamin D acts to promote the intestinal absorption of calcium and phosphate, and enhance renal reabsorption of calcium.[58],[59] Adequate vitamin D therefore supports calcium absorption and facilitates the accrual of bone mass.
PREVENTS BONE LOSS
After peak bone mass is reached in early adulthood, skeletal strength and BMD are negatively affected by persistent low calcium intakes, changes to calcium absorption and excretion or as a result of ageing. In menopausal women and men aged 55 years, bone balance naturally becomes negative, with bone loss at skeletal sites correlating with calcium losses of approximately 15 g per year.[60]
This is exacerbated by states of chronic calcium deficiency due to habitual inadequate intake, poor absorption or vitamin D deficiency. This causes the mineral balance to shift and stimulates the extraction of calcium from bone stores, at the expense of bone mass, for maintenance of circulating calcium.[61] As such, in older adults, achieving adequate calcium intake can help to maintain calcium storage within skeletal tissues and facilitate the retention of bone mass.
…In menopausal women and men aged 55 years, bone balance naturally becomes negative, with bone loss at skeletal sites correlating with calcium losses of approximately 15 g per year
In post-menopausal women, research has shown calcium supplementation to be more effective than placebo in reducing bone loss by the second year of supplementation.[62] In this population group, MCHC has shown greater efficacy and tolerability over calcium carbonate for the prevention of BMD decline.[63] Specific mechanisms associated with the ability of MCHC to support bone mass retention[64] include:
Decreasing bone resorption by delaying the development of precursor bone-remodelling cells, osteoclasts, involved in the remodelling and removal of aged bone matrix[65];
Moderating the activity of bone turnover enzyme, C-terminal telopeptide of type 1 collagen (CTX).[66]
The combination of boron and hydroxyapatite observed in in vitro studies on human cell lines has been demonstrated to influence signalling pathways involved in osteogenic differentiation within mesenchymal cells (MSCs), also known as stem cells,[67]promoting skeletal retention and bone matrix synthesis.[68] Additionally,
vitamin K-dependant proteins, osteocalcin and matrix Gla (MGP), promote bone matrix synthesis within skeletal sites, thereby supporting bone regeneration and retention.[69],[70]
Further, vitamin D promotes BMD retention, as well as maintaining dietary and supplemental calcium absorption.[71],[72] As such, adequate vitamin D in combination with calcium and other nutritional cofactors prevents the acceleration of net BMD losses that may increase the risk of osteopenia and osteoporosis.
SUPPORTS HEALTHY GESTATIONAL AND PREGNANCY OUTCOMES
Large amounts of calcium are required during pregnancy to support foetal growth and calcification.[73] Approximately 80% of foetal calcium is accumulated over the third trimester, peaking at a transfer rate of 300 mg to 350 mg in the final six weeks of pregnancy.[74]
After birth, infants require 200 mg/d calcium daily during the first six months, and 120 mg calcium during the following six months, with these values doubling and tripling in women who birth twins and triplets, respectively.[75]
Moreover, calcium’s role in maintaining healthy muscle contraction supports pregnancy outcomes by maintaining endothelial vascular function. Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the placenta to meet the needs of the developing foetus.[78]
Failure of the maternal vasculature to properly adapt (i.e. expand to promote placental circulation) can result in hypertensive disorders of pregnancy such as pre-eclampsia. Low calcium intake may cause high blood pressure by stimulating either parathyroid hormone or renin release from the kidneys, thereby increasing calcium in vascular smooth muscle leading to vasoconstriction.[79] As such, ensuring adequate calcium intake during pregnancy can prevent the consequences of lows intake to support gestational and maternal health outcomes.
Clinical research assessing the application of calcium in maternal populations indicates clear benefits in the supporting the management of pre-eclampsia,[112] as well as limiting maternal bone resorption during pregnancy (a mechanism which compensates for increased calcium needs at the expense of maternal bone mass).[113],[114]
In 2018, The Cochrane library published a meta-analysis of 13 studies contributing data from 15,730 women; 12 of these studies looking at the health benefits associated with 500 mg/d to 1000 mg/d of calcium from 34 weeks of pregnancy (i.e. third trimester).
These clinical trials featured women taking calcium alone (four trials), calcium combined with vitamin D (five trials) or calcium combined with antioxidants (three trials). Results indicated calcium supplementation lowered the risk of hypertension compared to placebo (risk ratio [RR] 0.65, 95% confidence interval {CI}) and modestly reduced the risk of pre-eclampsia (RR 0.45, 95% CI), an effect that was prominent in mothers with calcium-deficient diets and not individuals with calcium-adequate diets.[115]
Further, calcium supplementation was shown to reduce the risk of maternal death or serious comorbidity and pre-term birth, particularly in women at risk of pre-eclampsia.[116]
In 670 women taking 1,200 mg/g of calcium throughout their second and third trimester until the early postpartum period, calcium supplementation was shown to reduce bone resorption and prevent transient skeletal losses associated with pregnancy.[117]
Comparable outcomes were observed in a double-blind randomised placebo-controlled clinical trial conducted in 64 women supplementing 500 mg/d of calcium carbonate from 16 weeks gestation until 12 months after birth. Outcomes revealed the treatment group to experience greater increases in BMD at 12 months compared to placebo (p<0.02).[118] As such, evidence supports the benefits of supplemental calcium intake to support maternal health and pregnancy outcomes.
The combination of MCHC, boron, vitamin K1 and vitamin D with bone-matrix enhancing growth factors can be used to support calcium replenishment and maintain calcium intakes, strengthen bone health in all ages, limit BMD losses, maintain skeletal health during menopause, limit the negative effects of long-term corticosteroid use on BMD losses and ensure adequate calcium intake to support healthy gestation, pregnancy and lactation.
POST-MENOPAUSAL BONE HEALTH
Enhancing calcium intake has been shown to mitigate the rate of bone loss and reduce the risk of bone fracture in menopausal women.[93]
Clinical data outlines the efficacy of MCHC over calcium carbonate to prevent BMD losses based on the outcomes of a prospective, open-label controlled trial in 1,032 menopausal women with normal BMD or slight osteopenia.[94]
Women in the study were assigned either 712 mg/d of MCHC or 1,000 mg/d of calcium carbonate for three years and were assessed for BMD with dual energy X-ray absorptiometry (DXA)[†] at baseline, 18 months and after the trial (i.e. 36 months).
Women treated with MCHC maintained BMD scores (mean T-score increase of 0.01 [±0.82]), however women in the calcium carbonate group experienced BMD decline (mean T-score decrease of -0.23 [±0.76]), indicating superior efficacy of MCHC compared to calcium carbonate (p<0.01). Additional benefits included better tolerability profile of MCHC compared to calcium carbonate resulting in less digestive issues.
Moreover, findings from a prospective, comparative, non-randomised, open-label study in 851 perimenopause women with a DXA T score of -2 revealed MCHC to exert positive effects on BMD retention.[95]
In this trial, 712 mg/d of MCHC over three years was shown to stabilise BMD at lumbar vertebrae sites, L2 and L4 (i.e. -0.03% loss), compared to -3.1% regression observed in the calcium carbonate group (1,000 mg/d) [p<0.001] {Figure 4}.[96]
Based on these outcomes, researchers concluded that the greater benefits of MCHC could be attributed with the presence of bone growth factors that enhance bone matrix formation, thereby preventing BMD decline associated with menopause.[97],[98]
Further supporting the protective effects of MCHC, outcomes of a four-year retrospective follow-up study in 112 post-menopausal women aged 45 to 55 years receiving high doses of MCHC (3,320 mg/d) revealed that supplementation could revert osteopenic DXA scores.[100] In this trial, baseline trabecular BMD T and Z scores[‡] were -1.27 ± 0.7 and -1.03 ± 0.7 respectively, which improved to -0.86 ± 0.7 and -0.62± 0.7 after four years (p<0.0001). This finding suggests that MCHC provides an effective and safe strategy to protect bone mass in menopausal women.[101]
FRACTURE RISK / OSTEOPENIA AND OSTEOPOROSIS PREVENTION
MCHC has been demonstrated to reduce the rate of bone loss in osteoporosis more effectively than calcium carbonate.[102]
In a randomised, open-label, parallel-group, controlled study in osteoporotic women (n= 54), MCHC was more effective in lowering progressive BMD loss over three years. In this study, 712 mg/d elemental calcium (in the form of MCHC) paired with 266 µg/d (10,640 IU) of vitamin D retained lumbar spine mass more effectively than 1,000 mg/d of elemental calcium from calcium carbonate with the same dose of vitamin D (-1.1% vs. -2.3% loss; p<0.05; Figure 5).
Further, researchers identified a non-significant trend in increased femoral neck mass in both groups, however this outcome was more pronounced in the MCHC group, suggesting positive benefits of MCHC on skeletal health.
Further reinforcing these findings are outcomes from a meta-analysis of six high-quality, randomised, controlled clinical trials in patients with a clinical diagnosis of osteopenia, osteoporosis risk factors or osteoporosis.[104] In this study, it was determined that MCHC exerted a greater effect on bone mass retention compared to calcium carbonate, thereby limiting bone loss and reducing the progression of osteoporosis.[105]
Additional benefits of MCHC have been observed in combination with oestrogen-agonist medication, raloxifene, in preventing bone loss compared to calcium carbonate. In a randomised, open-label clinical trial in 90 osteopenic and osteoporotic women (baseline T scores -2.29), 712 mg/d of MCHC over three years was shown to prevent losses in bone mass more effectively than calcium carbonate (-18.72 m/s in the MCHC group vs. -63.64 m/s in the calcium carbonate group; p<0.006).[106] This supports the protective effect of MCHC combined with pharmaceutical medication to minimise progressive bone loss in osteoporosis.
Another interesting application of MCHC is its ability to mitigate bone losses associated with corticosteroids. Two separate studies have observed the protective effects of MCHC on steroid-induced decline in BMD.
In a randomised, controlled clinical trial, 37 patients were prescribed prednisolone at variable doses between 5 mg/d and 20 mg/d to manage conditions such as bronchial asthma in combination with 6 g/d to 8 g/d of MCHC over 12 months.[107] Results indicated that patients in the control group (n=7) experienced greater decreases in cortical bone thickness over 12 months compared to the treatment group (n=18) [i.e. -0.27 mm loss in controls vs. - 0.01mm in the treatment group] reported to reach near statistical significance in the small population sample.[108]
In addition to this, in a randomised-controlled trial, conducted in patients receiving 5 mg/d to 12.5 mg/d of prednisolone for the treatment of hepatitis, 8 g/d of MCHC administered over two years was observed to prevent progressive losses within trabecular bone volume compared to controls (p<0.025); indicating the protective effect of MCHC in mitigating medication-induced osteopenia and osteoporosis.[109]
As outlined previously, vitamin D works via multiple mechanisms to assist with BMD retention in osteopenia and osteoporosis, as supported by a large body of evidence. For instance, in a systematic review, vitamin D supplementation between 700 IU/d to 800 IU/d was shown to reduce the risk of hip and nonvertebral fractures in ambulatory or institutionalised elderly persons compared to 400 IU/d.[110]
Further, 800 IU/d of vitamin D combined with calcium may decrease the incidence of non-vertebral fractures by 10% to 20% in older individuals with lower baseline vitamin D,[111]supporting the importance of maintaining adequate vitamin D to mitigate fracture risk.
INGREDIENTS
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DIRECTIONS
Recommended Calcium Daily Intake
1 - 3 years: 500 mg/d
4 - 6 years: 600 mg/d
7 - 18 years: 1,300 mg/d
19 - 50 years: 1,000 mg/d
50+ years: 1,000 – 1,300 mg/d
Pregnancy: 1,200 mg/d
Lactation: 1,000 mg/d
Total equivalent Calcium per tablet: 366.5 mg
EVIDENCE
References
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[2] Khaliq H, Juming Z, Ke-Mei P. The physiological role of boron on health. Biol Trace Elem Res. 2018 Nov;186(1):31-51. doi: 10.1007/s12011-018-1284-3.
[3] van Driel M, van Leeuwen JPTM. Vitamin D endocrinology of bone mineralization. Mol Cell Endocrinol. 2017 Sep 15;453:46-51. doi: 10.1016/j.mce.2017.06.008.
[4] Palermo A, Tuccinardi D, D’Onofrio L, Watanabe M, Maggi D, Maurizi AR, et al. Vitamin K and osteoporosis: Myth or reality? Metabolism. 2017 May;70:57-71. doi: 10.1016/j.metabol.2017.01.032.
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[33] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
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[43] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
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[179] Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. In: Seminars in respiratory and critical care medicine. Thieme Medical Publishers. 2010;31(4):474-84.
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[190] University of Maryland medical Center. Possible interactions with calcium. [Online]. 2007. Available from: http://umm.edu/Health/Medical-Reference-Guide/Complementary-and-Alternative-Medicine-Guide/Supplement-Interaction/Possible-Interactions-with-Calcium. [Cited: 23/01/2017].
[191] Slatopolsky E, Bricker NS. The role of phosphorus restriction in the prevention of secondary hyperparathyroidism in chronic renal disease. Kidney Int. 1973 Aug;4(2):141-5. doi: 10.1038/ki.1973.92. PMID: 4355426.
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[202] Ghomian N, Hafizi L, Takhti Z. The role of vitamin C in prevention of preterm premature rupture of membranes. Iran Red Crescent Med J. 2013;15(2):113–116. doi:10.5812/ircmj.5138
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[204] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 458-63.
[205] Terrin G, Berni Canani R, Di Chiara M, et al. Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate. Nutrients. 2015;7(12):10427–10446. Published 2015 Dec 11. doi:10.3390/nu7125542
[206] Ota E, Mori R, Middleton P, et al. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2015;(2):CD000230. Published 2015 Feb 2. doi:10.1002/14651858.CD000230.pub5
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[208] Higdon J. An evidence-based approach to phytochemicals and other dietary factors. New York (NY): Thieme; 2003. p. 90 - 96.
[209] National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. Vitamin D [Internet]. Canberra (ACT): Australian Government. 2014 Sept 4. [cited 2020 Jul 30]. Available from: https://www.nrv.gov.au/nutrients/vitamin-d.
[210] Gropper SS, Smith JL. Advanced nutrition and human metabolism. 6th ed. Belmont (CA): Wadsworth; 2013. p 438-43.
[211] Gropper SS, Smith JL. Advanced nutrition and human metabolism. 6th ed. Belmont (CA): Wadsworth; 2013. p 463-7.
[212] National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. Vitamin D [Internet]. Canberra (ACT): Australian Government. 2014 Sept 4. [cited 2020 Jul 30]. Available from: https://www.nrv.gov.au/nutrients/vitamin-d.
[213] Calcium. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Nov 1; cited 2018 Feb 12]. Available from: www.naturaldatabase.com. Subscription required to view.
[214] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 464-98.
[215] Boron. In: Natural Medicines Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2019 [updated 2018/12/12; cited 2019/03/15]. Available from: URL. Subscription required to view.
[216] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 458-63.
[217] Vitamin K. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 March 7; cited 2018 Apr 27]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=983#adverseEvents. Subscription required to view.
[218] Higdon J. An evidence-based approach to phytochemicals and other dietary factors. New York (NY): Thieme; 2003. p. 90 - 96.
[219] National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. Vitamin D [Internet]. Canberra (ACT): Australian Government. 2014 Sept 4. [cited 2020 Jul 30]. Available from: https://www.nrv.gov.au/nutrients/vitamin-d
WARNINGS
Contraindications
Calcipotriene: Calcipotriene is a vitamin D analogue used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia. Avoid concurrent use.[119]
Calcitriol: Calcitriol is a vitamin D analogue and when used in conjunction with vitamin D supplements may have an additive effect and increase risk of vitamin D toxicity and hypercalcemia. Avoid concurrent use.[120]
Warfarin and indandione anticoagulants: These medications work by inhibiting conversion of the vitamin K epoxide back to vitamin K. Excessive vitamin K intake will interfere with the anticoagulant effect of these drugs unless closely monitored, and adverse effects can be rapid and serious. Avoid using.[121],[122],[123]
Cautions – Moderate level
Aluminium / aluminium-containing phosphate binders: The protein that transports calcium across the intestinal wall can also bind and transport aluminium. This protein is stimulated by vitamin D, which may therefore increase aluminium absorption. This mechanism may contribute to increased aluminium levels and toxicity in people with renal failure, when they take vitamin D and aluminium-containing phosphate binders long term.[124] In patients with renal failure it is recommended to exercise caution when taking this combination and to only do so under medical supervision.
Bisphosphonates (alendronate, etidronate, ibandronate, risedronate, tiludronate): Bisphosphonate medications contain phosphorus,[125],[126],[127] and bind with calcium in the gastrointestinal system.[128],[129] Closely monitor patients who are taking calcium and phosphorus alongside bisphosphonates and separate doses by two hours:Phosphorus: Taking bisphosphonates alongside supplemental phosphorus may have an additive effect leading to hypocalcemia and hyperparathyroidism.[130],[131],[132]
Calcium: Taking bisphosphonates alongside supplemental calcium may form insoluble complexes, reducing absorption of both calcium and bisphosphonates.[133],[134]
Calcium channel blockers: Calcium channel blockers increase intracellular calcium concentrations.[135]Hypercalcaemia may result if used concurrently with high doses of calcium (i.e. doses >2,000 mg/d),[136],[137],[138] and vitamin D (2,000 IU/d 50mcg/d).[139],[140],[141] Increased serum calcium may have an antagonistic effect that could precipitate the re-emergence of arrhythmias and/or an increase in blood pressure.[142],[143],[144] Use with caution in patients on calcium channel blockers.
Digoxin: High doses of calcium (>2,000 mg/d) and or vitamin D (>2000 IU/d [50mcg/d]) can induce hypercalcemia causing an increased risk of fatal cardiac arrhythmias with cardiac glycosides. Avoid high doses of calcium and vitamin D and use only under medical supervision.[145],[146],[147],[148],[149],[150]
End Stage Kidney Disease: Phosphorus is a mineral tightly regulated by the kidneys.[151] Those with end stage renal kidney disease have an impaired ability to excrete phosphorus and calcium and are often prescribed a low-phosphate diet.[152],[153] Closely monitor patients with kidney disease who are taking supplemental phosphorus, calcium and vitamin D and use only under medical supervision:
Phosphorus: Use of phosphorus in patients with end stage kidney disease may lead to hyperphosphatemia, hypocalcemia, hyperparathyroidism, and nephrocalcinosis.[154],[155]
Calcium: High dose calcium supplementation (i.e. doses > 2000 mg/day) should be avoided due to the risk of increased calcium accumulation. [156],[157],[158]
Vitamin D: Use of vitamin D in doses above 2,000 IU/d (50 µg/d) may cause hypercalcemia and should be avoided due to the risk of increased calcium accumulation. For doses under 2,000 IU/d, use caution and only under medical supervision.[159]
Hormone replacement therapies: Boron has been shown to stimulate oestrogen production and may theoretically augment the effects of oestrogenic medications and/or HRT. Evidence is lacking for claims of a significant adverse effects or increased risks attributable to boron supplementation at usual dosage levels of 1 to 3 mg/day. However, in a single-blind, placebo controlled, crossover trial, administration of boron at 10 mg/day for four weeks significantly increased plasma oestrodiol levels.[160],[161] Consider total boron intake. Monitor patients and cease use if adverse symptoms occur.
Hypercalcemia: Supplementation of calcium, phosphorus or vitamin D increases serum calcium. Use with caution and only under medical supervision in patients with hypercalcemia:
Calcium: High dose calcium supplementation (i.e. doses >2000 mg/d) increases the risk of increased calcium accumulation.[162],[163]
Phosphorus: Phosphorus may bind to serum calcium forming calcium phosphate in patients with hypercalcemia.[164] High serum levels of calcium phosphate may theoretically lead to soft tissue calcification.[165]
Vitamin D: Use of vitamin D in doses above 2,000 IU/d (50 µg/d) may cause hypercalcemia and should be avoided due to the risk of increased calcium accumulation.[166] For doses under 2000 IU, use caution and only under medical supervision.[167],[168]
Hyperparathyroidism: Hyperparathyroidism causes an overproduction of parathyroid hormone and a subsequent increase in serum calcium. High dose calcium supplementation (>2,000 mg/d),[169],[170] or Vitamin D (>2,000 IU/d [50 mcg/d]),[171],[172] increases the risk of hypercalcemia in patients with hyperparathyroidism. Use with caution and only under medical supervision.
Hyperphosphatemia: Phosphorus supplementation in patients with hyperphosphatemia may lead to a further increase in serum phosphate.[173],[174] Closely monitor phosphate levels and exercise caution in patients with hyperphosphatemia who are taking supplemental phosphorus.
Oestrogen-sensitive conditions: Boron has been shown to stimulate oestrogen production and may theoretically worsen symptoms associated with oestrogen excess in some female patients. Evidence is lacking for claims of a significant adverse effects or increased risks attributable to boron supplementation at usual dosage levels of 1 to 3 mg/day. However, in a single-blind, placebo controlled, crossover trial, administration of boron at 10 mg/day for four weeks significantly increased plasma estrodial levels.[175],[176]Those with oestrogen-sensitive conditions (e.g. breast, uterine, or ovarian cancer, endometriosis or fibroids) should therefore avoid supplemental boron at doses above 10 mg per day. Monitor patients and stop use if worsening of symptoms occurs.[177],[178]
Sarcoidosis or other granulomatous disease: Granulomatous inflammation increases the production of vitamin D and therefore the risk of vitamin D induced hypercalcemia.[179] Calcium supplementation (> 2000mg/day) and vitamin D (>2,000 IU/d [50 mcg/d]) should be avoided due to the risk of increased calcium accumulation in patients with sarcoidosis and other granulomatous diseases. For doses below 2000mg/day of calcium,[180],[181],[182] and 2,000 IU/d of vitamin D use with caution and only under medical supervision.[183],[184]
Thiazide diuretics: Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. Vitamin D induced hypercalcaemia has occurred in patients with hypoparathyroidism who were taking thiazide diuretics, and in those with normal parathyroid function who were also taking thiazide diuretics.[185],[186] Use combinations of thiazides and vitamin D with caution and monitor serum calcium levels.
Verapamil: Hypercalcaemia induced by high doses of vitamin D (i.e. doses >2,000 IU/d or 50 µg/d) can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above 2,000 IU (50 µg/d) daily and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.[187],[188]
Cautions – Low level
Atenolol: Calcium may form insoluble complexes with this medication reducing its absorption. Separate dose by at least two hours.[189],[190]
Kidney Disease: Phosphorus is a mineral tightly regulated by the kidneys. Those with kidney disease have an impaired ability to regulate minerals like phosphorus.[191] Use of phosphorus in patients with kidney disease may lead to hyperphosphatemia, hypocalcemia, and hyperparathyroidism.[192],[193] Monitor patients with kidney disease who are taking phosphorus.
Levothyroxine: Calcium administered concurrently may reduce drug absorption, separate doses by at least four hours.[194],[195],[196]
Sotalol: Calcium may form insoluble complexes with this medication reducing its absorption. Separate doses by at least two hours.[197],[198]
Pregnancy and Lactation
Pregnancy
Limited/unavailable research. A review did not identify any concerns for use during pregnancy,[199],[200],[201],[202], [203],[204],[205],[206],[207],[208],[209] however safety has not been conclusively established in humans. Pregnancy dosing restrictions pertaining to ingredients are as follows:Phosphorus: There is evidence to support the use of phosphate during pregnancy at recommended dietary allowances (RDAs) of phosphate (700mg/day).[210],[211]
Vitamin D: Vitamin D is safe when used in doses below the tolerable upper intake level (UL) of 80 µg (3200 IU) per day.[212]
Breastfeeding
Appropriate for use.[213],[214],[215],[216],[217],[218],[219]
Children
No information available.
MGXCP
