These are the questions we’ve been tackling at Natural Calm, in response to some not-so-factual claims.
It’s time to take our fact-finding one step further. Here, Dr. Alison Smith explains the results of a new clinical trial comparing four popular magnesium supplements on the Canadian market.
Busting myths about magnesium supplements with the results from a new clinical trial
By Dr. Alison Smith, PhD, Neuroscience
Feel like being a myth-buster today?
There’s nothing that gets me more excited than discovering truth in science and busting myths! Especially when those myths affect how people spend their hard-earned money.
But, in the natural supplement industry, how does an average consumer discover the truth about the supplements they buy? How can consumers tell if the scientific evidence companies use to back up their claims is actually scientifically valid or just made up?
Let’s start off with this question…
Are you being misled about the effectiveness of some magnesium supplements on the market? This question has been a real concern here at Natural Calm Canada because the answer is often yes –– many Canadians are being fed misinformation about magnesium absorption.
That’s why we’re excited to share the results of a new clinical trial. In many ways, it is the first of its kind, and while preliminary, it is certainly a big step towards busting myths!
But first, let’s talk about the myths vs. the real science. (If you want to skip to the clinical trial results, scroll down.)
Magnesium Absorption Myths
Around January 2017, Natural Calm asked me to help interpret the scientific evidence on magnesium absorption and help counter some dubious claims with credible science. I’m a trained neuroscientist, university course instructor, and a science advisor/medical writer for supplement companies in Canada.
Two supplement companies in Canada, in particular, have been making the claim that magnesium glycinate (also known as magnesium bisglycinate or diglycinate) is the most absorbable and bioavailable form of magnesium on the market.
Here’s exactly what the dubious claims say…
Claim #1:• “You would have to take 4 times the amount of magnesium citrate to get the equivalent amount of magnesium bisglycinate.” (no source cited)
Claim #2: “Magnesium bisglycinate appears to be the safest and most effective form of magnesium for human absorption according to a magnesium research review published in the European Journal of Orthomolecular Medicine (Siebrecht, 2013).” [By the way…the journal that was originally referenced doesn’t exist. The article is actually located within the International Journal of Orthomolecular and Related Studies.]
Now, the question is…are these claims true? And, are they backed-up by scientific data? Is magnesium glycinate more effective than other organic magnesium salts including magnesium citrate?
What Does the Science Say?
To evaluate the claims in the quotes above, Natural Calm Canada took two steps.
- They commissioned a full clinical study on magnesium absorption, comparing Natural Calm against 3 other popular magnesium brands in Canada, including the two brands quoted above.
- They hired Dr. Jon Paul Powers, a microbiologist, partner, and scientific advisor with Gowling WLG in Ottawa, to write a scientific white paper on the effectiveness of magnesium citrate in comparison to other forms of magnesium on the market using data from all the current peer-reviewed literature about magnesium absorption.
Dr. Powers’ research was published on this website in May, 2017. You can read my summary of the literature review on magnesium absorption here.
The key takeaway is this: until September 2017, there had never been any scientific study comparing magnesium glycinate against magnesium citrate. In fact, very few scientific studies have compared magnesium glycinate against other magnesium salts at all.
What published research does exist suggests that magnesium citrate is at least as absorbable as magnesium glycinate.
We know this much from the existing, peer-reviewed, published science.
But now we also have the results of the new clinical study comparing magnesium supplements head-to-head.
Understanding the New Clinical Study on Magnesium Absorption
Even though the white paper by Dr. Powers helped us better understand magnesium absorption, it also highlighted how little scientific research there was comparing the absorption rate of the varying types of organic magnesium salts.
Natural Calm recognized the need for more research measuring magnesium absorption in the human body.
That’s why Natural Calm sponsored a full clinical study comparing Natural Calm magnesium citrate against three other major magnesium supplement brands — including those brands that have been making claims about magnesium glycinate.
I can’t stress enough to you how utterly rare it is for a relatively small company to take this step! Natural Calm spent a significant amount of money to advance what we know about magnesium absorption, without being sure what the results would say.
The results of the clinical trial came out in September 2017, so please be aware that this study hasn’t been published yet. We are in the process of submitting it for publication in a peer-reviewed journal.
However, we decided to release the results now, before publication, because they’re important.
First, I’ll explain the study design, because it’s important to understanding the fascinating results.
Clinical Study: Background
Natural Calm Canada hired Nutrasource: a Canadian full-service contract research organization (CRO) that specializes in clinical trials for the natural supplement industry.
Nutrasource designed a randomized, double-blind, placebo-controlled clinical trial that compared the performance between:
1. Natural Calm magnesium citrate powder
2. CanPrev magnesium bisglycinate powder
3. Lorna Vanderhaeghe magnesium bisglycinate powder (Magsmart®)
4. Natural Factor’s magnesium citrate capsule
Clinical Study Design: Key Terms
It’s easy to get lost in the terminology of a scientific study, so let’s take a minute to sift through key terms.
This study was randomized, double-blinded and placebo-controlled, but what does that mean?
- Randomized –– Randomized clinical studies provide the most reliable form of scientific evidence because they eliminate subject selection bias. An investigator is not allowed to hand-pick subjects for their study groups; that practice would introduce a personal bias into the study and reduce the study’s validity.
- Double-Blinded –– This means that the investigator giving the supplements to the subject has no idea which supplement the subject is receiving, and the subject doesn’t know which supplement they’re receiving either. Both investigator and subject are blinded. This method increases the validity of a study by reducing personal biases that could distort the results.
- Placebo-Controlled –– Administering a placebo ensures that any changes in magnesium concentration in the blood serum or urine is in response to taking the various magnesium supplements rather than taking just a placebo.
Clinical trials that are randomized, double-blinded, and placebo-controlled are of the highest calibre, and results from such a study design are more valid and reliable than running a study without those controls in place.
It’s also important that this study was in vivo, measuring absorption in human subjects, rather than models or cells extracted and studied in petri dishes.
Clinical Study Design: Methodology
The 10-week clinical trial involved 12 (a standard sample size for initial studies of this type) healthy, postmenopausal women, with an average age of 53. This population was chosen because it represents the primary customer of Natural Calm. Also, female hormonal fluctuations associated with menstruation influence magnesium absorption; therefore, choosing a postmenopausal population was necessary to control for such fluctuations.
Subjects went to the Nutrasource testing facility in Guelph, Ontario on 27 separate occasions.
Subjects were randomized to one of four testing sequences.
There were five separate test periods to measure magnesium concentration in the blood serum and urine after taking one of the four magnesium supplements or the placebo.
During each of the five test periods, subjects were given one of five potential treatments, including 150 mg of:
- Natural Calm magnesium citrate powder
- CanPrev magnesium glycinate powder
- Lorna Vanderhaeghe magnesium glycinate powder
- Natural Factor’s magnesium citrate capsule
Investigators ensured that each subject’s bloodstream was cleared of a magnesium supplement before exposing the subject to the next magnesium supplement.
Blood was taken every hour for 12-hours after taking the supplement or placebo.
Urine was collected for 24-hours.
Clinical Study Design: Measures
1. The primary measure in this study was the concentration of magnesium within the blood serum and urine between 0-8 hours after taking the four different magnesium supplements or the placebo.
2. To make sure that no stone was left unturned, there were 10 other secondary measurements including:
i. Blood serum magnesium between 0-10 hours.
ii. Blood serum magnesium between 0-12 hours.
iii. Maximum concentration of blood serum magnesium (Cmax).
iv. Time of maximum concentration of blood serum magnesium (Tmax).
v. Urine magnesium between 0-10 hours.
vi. Urine magnesium between 0-12 hours.
vii. Urine magnesium between 0-24 hours.
viii. Maximum concentration of urine magnesium (Cmax)
ix. Time of maximum concentration of urine magnesium (Tmax)
x. 24h urine magnesium (total)
Why Measure Magnesium in the Blood Serum and Urine?
The process of magnesium absorption is complex, and measuring magnesium absorption in the human body is difficult. Magnesium concentration within the blood serum is influenced by:
- Hormonal fluctuations in the female premenopausal population.
- Circadian rhythm (A 24-hour cycle of a physiological process.)
- The body’s natural regulation of magnesium concentration in the blood (homeostasis).
To overcome the challenges of measuring magnesium absorption, researchers have developed three measuring models:
- Measuring magnesium absorption in the blood after a subject takes a magnesium formulation that contains a radio-labelled magnesium.
- Measuring intracellular magnesium concentration within red blood cells to assess long-term magnesium absorption.
- Measuring acute magnesium concentration in the blood serum and urine following an oral dose of magnesium.
The investigators of this study chose to measure magnesium concentration in the blood serum and urine for three reasons:
- Measuring magnesium concentration in excreted urine is documented as a reliable measure of magnesium absorption when magnesium is held in a consistent balance. It’s also a readily available method to measure acute magnesium absorption. [4-7] a) Quamme GA. 1993 Magnesium homeostasis and renal magnesium handling. Miner Electrolyte Metab.;19:218-255; b) Kayne LH, Lee DB. 1993 Intestinal magnesium absorption. Miner Electrolyte Metab.;19:210-217; c) Siener R, Jahnen A, Hesse, A. 2011 Bioavailability of magnesium from different pharmaceutical formulations. Urol Res.;39:123-127; d) Niazi SK. Handbook of Bioequivalence Testing, Second Edition (Drugs and the Pharmaceutical Sciences). CRC Press. Taylor and Francis Group. Boca Raton Florida. 2015.
- Blood serum concentration of magnesium is not a perfect measure; however, it is used regularly in peer-reviewed publications. (Please visit PubMed.com, and search for blood-serum and magnesium studies.) To increase the validity of this method the investigators followed the European Medicine Agency guidelines on measuring the bioavailability of magnesium by subtracting out a subject’s baseline level of magnesium before running any statistical analysis. This helped to control for the subject’s natural level of magnesium in their blood, and helped to ensure that the statistical analyses were not skewed. e) European Medicines Agency. Guideline on the Investigation of Bioequivalence. London, 20 January 2010.
- This study was interested in measuring acute versus long-term changes in magnesium concentration within the blood serum and urine. Therefore, measuring intracellular magnesium concentration was not chosen. Intracellular methods are also not cost-effective or as readily available as blood serum and urine methods. Intracellular methods are also just as problematic as blood serum measurements. When it comes to measuring the bioavailability of magnesium, there is no perfect measurement method.
People sometimes guess that magnesium in the urine means it hasn’t been absorbed. The reverse is actually true!
Magnesium showing up in the urine is a good thing.
The most important thing about a magnesium supplement is its ability to be absorbed and to become bioavailable. Bioavailability means that the magnesium is within the bloodstream, and it can be used for physiological functions.
For magnesium to end up in the urine, it has to be bioavailable first. When you ingest a magnesium supplement, it doesn’t simply travel to the kidneys first and end up in the urine. No. The magnesium supplement must first be absorbed through the intestine, and then circulate throughout the body (bioavailability), before it is processed and eliminated by the kidneys through the urine.
Measuring magnesium concentration in the urine is not a perfect way to measure the bioavailability of magnesium in the body, but it is a measurement method that is routinely used in peer-reviewed scientific studies that are available to read through PubMed.com.
So, keep this in mind: The more absorbable and bioavailable a magnesium supplement is, the more magnesium will show up in the urine.
Magnesium Absorption Study Outcomes: What We Know From Clinically Comparing Natural Calm Against 3 Other Popular Magnesium Supplements
Primary Measurement: Blood Serum
Remember, the primary measurement in this study was the concentration of magnesium within the blood serum and urine between 0-8 hours after taking a magnesium supplement or a placebo.
This clinical study found that Natural Calm magnesium citrate powder significantly increased the concentration of magnesium in both the blood serum and urine between 0-8 hours compared to the placebo.
The bisglycinate supplements from CanPrev and Lorna Vanderhaeghe, or the magnesium citrate capsules from Natural Factors, did not cause a significant increase in magnesium in the blood or urine compared to taking a placebo.
This result provides evidence that Natural Calm magnesium citrate powder has the capability to significantly increase the bioavailability of magnesium in the human body.
Secondary Measurements: Urine 0 – 12 Hours
From the secondary measurements, it was found that the concentration of magnesium in the urine between 0 – 12 hours was significantly greater following the administration of Natural Calm magnesium citrate versus Lorna Vanderhaeghe magnesium bisglycinate (Magsmart®).
One of the original claims about magnesium glycinate stated that you would have to take four times the amount of magnesium citrate to get the equivalent amount of magnesium bisglycinate in the body. Well….this result shows that that claim just isn’t true.
Secondary Measurements: 24-Hour Urine Cmax
The maximum concentration of magnesium in the urine (Cmax) was also measured after collecting urine over the course of 24 hours. Cmax was a secondary study measure.
Results showed the Natural Factors magnesium citrate capsule to significantly increase magnesium concentration in the urine compared to Lorna Vanderhaeghe’s magnesium bisglycinate supplement.
What exactly does this Cmax test result tell us?
Well, it’s a measure of how much magnesium enters into the bloodstream over the course of a 24-hour time window, after taking a magnesium supplement. The Cmax test result from this study tells us that magnesium concentration in the body after taking the Natural Factors magnesium citrate capsule was significantly higher than taking the Lorna Vanderhaeghe magnesium bisglycinate powder.
This result gives us a second piece of evidence that the claim by Lorna Vanderhaeghe that you would have to take 4 times the amount of magnesium citrate to get the equivalent amount of magnesium bisglycinate just isn’t true.
Why aren’t there any results for Natural Calm magnesium citrate or CanPrev magnesium bisglycinate for the Cmax test? All of the different treatments were compared against each other, but the only statistical difference was between Natural Factor’s and Lorna Vanderhaeghe.
What’s the Take-Home Message from this Clinical Study?
Overall, the results showed that the magnesium citrate supplements from Natural Calm and Natural Factors outperformed both magnesium bisglycinate supplements.
Let’s Just Stick to the Facts:
We don’t want to give the impression that Natural Calm or that magnesium citrate is the only absorbable form of magnesium on the market.
The scientific literature tells us that all organic magnesium salts are more soluble, absorbable, and bioavailable than inorganic magnesium salts, taken orally.
Magnesium glycinate isn’t any better than other organic magnesium salts including magnesium citrate.
The pool of research investigating which organic magnesium salt is the best is so incredibly small, so at this point, we can’t crown a winner.
The claims about magnesium glycinate were so loud. I’ve heard the claims even before I started working with Natural Calm.
All consumers have a right to the most up-to-date information on the products that they purchase –– and that information must be based on scientific data!
Now we know from both study results and the published literature that magnesium citrate is an effective, absorbable, bioavailable form – at least equal to, if not more absorbable than magnesium glycinate.
1. Ranade and Somberg (2001). Am J Ther. 8(5), 345-357.
2. Lindberg et al. (1990). J Amer Col Nutr. 9(1), 48-55.
3. Walker et al. (2003) Magnes Res 6(3), 183-91.
4. Quamme GA. 1993 Magnesium homeostasis and renal magnesium handling. Miner Electrolyte Metab.;19:218-255;
5. Kayne LH, Lee DB. 1993 Intestinal magnesium absorption. Miner Electrolyte Metab.;19:210-217;
6. Siener R, Jahnen A, Hesse, A. 2011 Bioavailability of magnesium from different pharmaceutical formulations. Urol Res.;39:123-127;
7. Niazi SK. Handbook of Bioequivalence Testing, Second Edition (Drugs and the Pharmaceutical Sciences). CRC Press. Taylor and Francis Group. Boca Raton Florida. 2015.
8. European Medicines Agency. Guideline on the Investigation of Bioequivalence. London, 20 January 2010.