Benefits vs. Risks of Strontium Supplements?

[Dean Pomerleau]

Strontium is one of the few supplements I still take, for bone health. But the new alert from Al Pater (thanks Al!) has got me wondering if this is wise.

 

The news story (included below), talks about Canada putting warning labels on supplements and pharmaceuticals containing strontium. It cites [1], a European study that found increased risk of cardiovascular events in at-risk individuals taking strontium.

 

On the other hand, the introduction of [1] points out that strontium really does appear pretty effective at building/maintaining bone health.

 

Plus, from [1], it doesn't sound like someone WITHOUT CVD risk factors should be worried, but we're all a lot more paranoid about supplements in general these days, so I'm still a bit concerned.

 

I take a 680/mg strontium capsule (as strontium citrate) per day. Study [1] talks about strontium ranelate, but I'm not sure if that makes any difference, since the Canadian authorities are talking about warnings for all strontium supplements, including strontium citrate.

 

I'm hoping someone with deep expertise in supplements and nutrition (I'm looking at you Michael :-) ) will be able to shed some light on the wisdom or folly of strontium supplements for CR practitioners.

 

Thanks!

 

--Dean

 

----------------

 

http://www.cbc.ca/news/health/strontium-1.3284679

 

Strontium health products may carry heart risks: Health Canada

Affected products products contain either strontium citrate, strontium gluconate or strontium lactate.

CBC News Posted: Oct 22, 2015 5:23 PM ET| Last Updated: Oct 22, 2015 5:23 PM ET

 

Health Canada has asked companies to strengthen their labels on natural health products containing strontium to warn of an increased risk of heart-related side-effects.

 

The department said Thursday the label changes are for strontium-containing products with a daily dose between 4 mg and 682 mg, which are used to help support bone mineral density.

 

Health Canada says findings in Europe led to restrictions for use of oral prescription drugs containing strontium at 680 mg/day, due to the increased risk of cardiovascular events seen in patients who have risk factors for heart or circulatory-related side-effects.

(Sean Kilpatrick/Canadian Press)

 

The products contain either strontium citrate, strontium gluconate or strontium lactate.

 

Under the new directions, use of the products will be limited to people who have no history of, or risk factors for, heart disease, circulatory problems or blood clots.

 

"While uncertainties remain, Health Canada is using a precautionary approach and considers that strontium, regardless of the form it comes in or dose taken, may have a potential risk of cardiovascular side-effects in people who are already at risk," it said.

 

Health Canada recommends:

 

Do not use a strontium-containing product if you have, or are at high risk for heart disease, circulatory problems, or blood clots. Risk factors include: a history of heart disease, heart attack, stroke, peripheral arterial disease, high blood pressure, high blood fat levels, diabetes, taking prescription hormone drugs, or if you are temporarily or permanently immobilized.

 

If you have any cardiovascular risk factors, read the label of products you are taking to know if they contain strontium.

 

Consult a healthcare practitioner for use beyond six months.

 

Talk to a healthcare practitioner if you have questions or if you are unsure whether these products are appropriate for you.

 

----------------------

[1] Expert Opin Drug Saf. 2014 September; 13(9): 1209–1213.

 

Published online 2014 July 14. doi: 10.1517/14740338.2014.939169

 

PMCID: PMC4196504

 

Cardiac concerns associated with strontium ranelate

 

Abstract

 

Introduction

 

Strontium ranelate is proven to reduce vertebral and non-vertebral fracture risk in osteoporosis. Concerns about cardiac safety have led to a new contraindication to strontium ranelate in patients with uncontrolled hypertension and/or current or past history of ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

 

Areas covered

 

A literature search was performed; data were also collected from the European Medicines Agency website. Randomised controlled trial (RCT) data indicate a higher incidence of non-adjudicated myocardial infarction (MI) with strontium ranelate versus placebo (1.7 vs 1.1%; odds ratio [OR]: 1.6; 95% CI: 1.07 – 2.38; p = 0.020) (Mantel-Haenzel estimate of the OR). There was no increase in cardiovascular mortality. MI risk was mitigated by excluding patients with cardiovascular contraindications (OR: 0.99; 95% CI: 0.48 – 2.04; p = 0.988). Three observational studies performed in the context of real-life medical practice in the UK and Denmark did not report a signal.

 

Expert opinion

 

The increased risk for cardiac events with strontium ranelate has been detected in RCTs but not in real life. Excluding patients with cardiovascular contraindications appears to be an effective measure for controlling the risk of MI. Strontium ranelate remains a useful therapeutic alternative in patients with severe osteoporosis without cardiovascular contraindications who are unable to take another osteoporosis treatment.

 

Keywords: cardiac safety, myocardial infarction, osteoporosis, strontium ranelate

 

Go to:

 

1.  Introduction

 

Strontium ranelate, an osteoporosis medication registered in Europe in 2004, has been studied in a range of randomised controlled trials (RCTs) [1-6]. It was originally indicated for the treatment of women with postmenopausal osteoporosis to reduce the risk for vertebral and hip fracture. The efficacy of strontium ranelate for preventing fracture in osteoporosis is well established, having been demonstrated in two pivotal RCTs – Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and TReatment Of Peripheral OSteoporosis (TROPOS) [2,3]. SOTI showed that, over 3 years, treatment with strontium ranelate 2 g/day reduced the risk of vertebral fracture in postmenopausal osteoporotic women and increased lumbar spine bone mineral density [2]. Strontium ranelate was demonstrated to have an effect on non-vertebral fracture (including hip) in postmenopausal osteoporotic women in TROPOS [3]. Strontium ranelate also increases bone mineral density in osteoporotic men [4], and there is evidence that its antifracture efficacy is maintained up to 10 years [5,6].

[Michael R]

Yeah, I became aware of this at the time of the European Medicines Agency's pharmacovigilance report on Protelos, and I'm pleased to see that Health Canada is both empowered and awake enough to force supplements to carry the warning (tho' putting it on supps with as low as 4 mg is kind of silly — and even sillier, since I expect that such supps probably are combo formulas with calcium, which will further limit its absorption). Canada actually has regulations on dietary supplements! Imagine!

That said, starting shortly after the EMAC originally raised concerns, a bunch of patient registry studies have been done (in countries where they can systematically track health outcomes and prescriptions in entire populations), along with some other epiedemiological studies, along with some studies on its effects on thrombotic factors thought to explain the increase in venous thromboembolism and MI (one of the trials from which the original warnings had emergted reported an increase in Factor VII levels), and there just doesn't seem to be anything there.

This is worth keeping an eye on, but as things stand now I think it's worth the risk for me and to take 340 mg elemental strontium. This is half the standard dose for full-on osteoporosis, but was used favorably in at least one study in perimenopausal osteopenic women, which is closer to my clinical condition — and plus, I have decades to maintain those bones, unlike the high-risk women in the osteo trials. I think that serious CR practitioners should consider doing the same, based on assessment of their own risk profile: I, and many other serious CR people, are at very low background risk of CV events generally, with a decreased tendency to thrombosis, but at significantly elevated fracture risk due to thinner bones and a very low anabolic tone (even if you're young enough that it will only become meaningful in any absolute sense decades into the future — see the FORE FRC fracture risk assessment calculator^*).

 

Do also remember, in all of this, that DEXA-measured BMD, which is the major data input for all available risk algorithms, is a highly imperfect test for most of us: it significantly underreports real bone mineral density in very slim people (see Archives, or studies by Bolotin), and also (per contra) that because of its greater molar mass than calcium, the incorporation of Sr into bone tissue following strontium supplementation artificially inflates DEXA BMD, over and above the real effects it has in bone anabolism: "Available data indicate that these factors account for approximately 50% of the measured change in BMD over 3 years of treatment with PROTELOS 2 g/day [=680 mg elemental Sr]."

And in case anyone is wondering: no, I do not believe that the form (ranelate vs. citrate) makes any difference here: anything we can nail down for the drug (ranelate) is IMO almost certainly going to apply to citrate or carbonate.

^* I have previously recommended the WHO FRAX calculator. However, the FORE tool (a) uses more data specifically on fracture risk in men, and (b) is more accurate in populations with a life expectancy >10 years, which I trust most of us do!).

[Dean Pomerleau]

Thanks Michael,

 

An amazingly thorough and timely response, as usual!

 

I actually realized after posting that I take a 680mg strontium (citrate) supplement every two days, so only 340mg/day, as you recommend.  I'll continue to follow this regime to support bone health until/unless additional evidence emerges for adverse effects of strontium in people like us, with low risk of CVD.

 

Thanks again,

 

--Dean

[Zeta]

A lot of us are eating a lot of veggies from California, which, based on what I dug up ages ago, would be likely to have lots of strontium. I decided at the time there was no reason to take supplemental strontium.

 

23andMe customers: take a look at rs6025. If you've got an A (which might show up as a T from the other strand), strontium might be slightly riskier.

 

Zeta

[Dean Pomerleau]

Thanks Zeta,

 

A lot of us are eating a lot of veggies from California, which, based on what I dug up ages ago, would be likely to have lots of strontium. I decided at the time there was no reason to take supplemental strontium.

 

I could be wrong (and please correct me if so), but I suspect you conflated two things in the analysis you are recalling. I suspect the high level of strontium in veggies in general, and California veggies in particular, is in reference to the results of studies like [1], containing tables like this one:

 

 

What studies like this found was that veggies and other plant foods can absorb strontium-90 in trace amounts, which BTW is further concentrated in animal products derived from animals that eat the plants, but I digress...

 

Strontium-90 is a radioactive isotope of elemental strontium produced by nuclear fission and found in some US soil as a result of above-ground nuclear testing. Notice the publication date on [1] - 1960. Since the half-life of strontium-90 is only 28 years, and since above-ground nuclear testing was banned (at least on US soil) in 1963, the strontium-90 "problem" in veggies (if it ever was a problem) should be pretty minimal by now, and irrelevant for the elemental strontium we're talking about in supplements anyway.

 

Elemental strontium, as opposed to strontium-90, appears quite beneficial for bone health, based on this introductory paragraph from PMC4196504 referenced above:

 

Strontium ranelate, an osteoporosis medication registered in Europe in 2004, has been studied in a range of randomised controlled trials (RCTs) [1-6]. It was originally indicated for the treatment of women with postmenopausal osteoporosis to reduce the risk for vertebral and hip fracture. The efficacy of strontium ranelate for preventing fracture in osteoporosis is well established, having been demonstrated in two pivotal RCTs – Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and TReatment Of Peripheral OSteoporosis (TROPOS) [2,3]. SOTI showed that, over 3 years, treatment with strontium ranelate 2 g/day reduced the risk of vertebral fracture in postmenopausal osteoporotic women and increased lumbar spine bone mineral density [2]. Strontium ranelate was demonstrated to have an effect on non-vertebral fracture (including hip) in postmenopausal osteoporotic women in TROPOS [3]. Strontium ranelate also increases bone mineral density in osteoporotic men [4], and there is evidence that its antifracture efficacy is maintained up to 10 years [5,6].

 

For more on the distinction between elemental strontium and strontium-90, as well as food sources of elemental strontium see this link. Preview - milk and milk products are the richest source of elemental strontium, containing about 1mg / liter. You'd have to drink a lot of milk to get the 340mg/day that Michael recommends...

 

In short, don't be too quick to throw out the elemental strontium baby with the (formerly) radioactive, strontium90-contaminated bathwater  .

 

23andMe customers: take a look at rs6025. If you've got an A (which might show up as a T from the other strand), strontium might be slightly riskier.

 

Thanks for the pointer. According to 23andMe I'm CC for rs6025, so I don't have an elevated risk of thrombosis that might be a counter-indicator for strontium supplementation.

 

--Dean

--------------

[1] Harley, John H. & Rivera, Joseph. (1960) Summary of Available Data on the Strontium 90 Content of Foods and of Total Diets in the United States. UNT Digital Library. http://digital.library.unt.edu/ark:/67531/metadc13122/. 

[Michael R]

Dean has covered the strontium90/stable strontium thing very nicely (thanks!). Per one of the authors of (1), "Strontium intakes ranged from 490 to 1,390 µg/day (10) [i.e., 0.490 to 1.390 mg/d]. Strontium was obtained primarily from grains and grain products; vegetables; and mixed dishes and soups. Milk, yogurt, and cheese were major sources of strontium for infants and 2-year-old children, while beverages were the major source for adult males. Strontium levels were highest in fried shrimp, some vegetables, pecans, breads, cheeses, some fruits, and chocolate powder."
 
Here are the exposure data from Table A18.1 in the Appendix to the 23rd Australian Total Diet Study:

 

 

Bah ... THAT didn't work! Anyway, the mean intake for adults was 1.9 mg/d, and the 90th percentile intake was 3.0 mg/d.

 

 

Reference
1: Pennington JA, Jones JW. Molybdenum, nickel, cobalt, vanadium, and strontium in total diets. J Am Diet Assoc. 1987 Dec;87(12):1644-50. PubMed PMID: 3680822.

[Zeta]

Thanks Dean and Michael, for the interesting info.

 

No, I wasn't thinking of the strontium-90 scare. I was moving from California a long time ago and knew that mineral content of soil could vary - a lot in the case of some minerals - and found a cool map showing levels of trace minerals in the soil of various places in North America. I was curious about whether I needed to change my mineral supplement strategy after my move. Anyway, I remember seeing strontium shown as high in California soil.

 

But, but, to be sure -- even the high end of the range of typical ingestion in California (if what I saw was accurate) would be nowhere near the therapeutic levels used in the intervention studies. My decision at the time was based on the idea that I don't want to supplement with freakishly high levels of anything without very good reason. Now, as opposed to then, we have a few well-conducted studies showing benefit to large doses. But it still makes me nervous.

 

I'll have to think about it a bit more. (And, alas, another bad roll of the dice for me, SNP-wise: I'm heterozygous for Factor V Leiden.... A small factor in the strontium decision, but still.)

 

Zeta

Edited October 27, 2015 by Zeta

[InquilineKea]

How about strontium chloride rather than strontium ranelate?

From a friend:

 

Quote

 

Stitches started to feel inflamed and itchy. I realized I could use strontium chloride as a treatment topically to eliminate inflammation.

https://patentimages.storage.googleapis.com/7c/63/ac/049c94fcd606b1/EP1605955B1.pdf

 

Strontium isn't 'officially' considered essential to animals. I think that it is. Strontium competes with calcium and moderates its effects. Calcium signaling is at the heart of many types of inflammation. Strontium is like calcium's slower, mellower brother (Sr²⁺ and Ca²⁺) are 'neighbors' on the periodic chart.

I think that supplementing strontium can reduce the overall pain and inflammation people have, and it is present in sea life (seaweed) and if you are close to the ocean, it finds its way into plants and animals. (See quantities in chicken eggs in Italy, for example-https://link.springer.com/content/pdf/10.1007/s10661-016-5316-1.pdf)

 

I don't want you to start talking to everyone on Facebook about strontium, I think that this is one of the pieces to the longevity formula. I want to add this to the anode electrolyte solution so that strontium is absorbed via the skin.

 

Strontium is well tolerated, even in very high doses. It should be part of our nutrient repertoire. Applied topically, it has some pretty powerful anti-inflammatory effects.

 

https://www.nature.com/articles/srep36251 

 

https://www.atsdr.cdc.gov/ToxProfiles/tp159-c1-b.pdf 

strontium phs - atsdr.cdc.gov Title: Microsoft Word - strontium_phs.doc Author: hga0 Created Date: 8/24/2004 2:42:56 PM www.atsdr.cdc.gov



"Studies in animals suggest that infants may absorb more strontium from the intestines than adults. If a fluid mixture of a strontium salt is placed on the skin, the strontium

will pass through the skin very slowly and then enter the bloodstream. If the skin has scratches or cuts, strontium will pass through the skin much more quickly."

 

"Ordinary strontium salts are not harmful when inhaled or placed on the skin."

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897514/

Effect of Strontium Chloride on Experimental Bladder Inflammation in Rat - PubMed Central (PMC) Introduction. Strontium salts are anti-irritants for chemically induced sensory irritation. Interstitial cystitis is a painful disease without definitive therapy. The aim of the study was to determine the effect of strontium in bladder with experimental ... www.ncbi.nlm.nih.gov

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897514/

"In our model, strontium did not make any significant changes in histopathology or histamine levels; however, it significantly reduced the levels of TNF-α."

 

https://www.hindawi.com/journals/bmri/2014/530687/

Strontium Chloride: Can It Be a New Treatment Option for Ulcerative Colitis? - Hindawi Background/Aims . Patients with ulcerative colitis still need effective therapy without major side effects. It has been found that strontium can suppress NF κ B activation induced by TNF- α . This opens a gate to a new anti-TNF agent which is cheap and can be given orally. We for the first time aimed to investigate the effect of strontium chloride (SrCl<sub>2</sub>) on inflammation in ... www.hindawi.com

https://www.mdedge.com/rheumatology/article/45498/rheumatoid-arthritis/novel-topical-agent-eased-osteoarthritis-pain

 

"Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300177/

 

Here are clinical trials:

https://clinicaltrials.gov/ct2/show/NCT00592098

https://clinicaltrials.gov/ct2/show/NCT00804375

 

You mean from strontium ranelate?

I am talking about strontium chloride.

 

Strontium ranalate is like a 3-legged sack race. Strontium is the athlete, and ranalate is a really poor partner. The only reason Sr ranelate exists is because it gave a pharmaceutical company the chance to patent and get approval for something that is open-source.

 

It is so stupid that they did this, because the ranelate is causing issues. 

Strontium is a natural part of the human diet, especially if you live near the coast. The differences seen with the strontium ranalate were really small. It wasn't a huge heart attack risk.