Magnesium Citrate Absorption and Bioavailability

more absorbable magnesium

Table of Contents

Any time you choose a supplement, you should make sure it’s absorbable. Magnesium is no exception. Magnesium must be absorbed through the gut into the bloodstream to benefit your health.

One of the most popular forms of this mineral supplement is magnesium citrate. So, what do we know about magnesium citrate absorption?

As it turns out, we know quite a bit and can compare how “bioavailable” or absorbable magnesium citrate is compared to other forms.

In this post, we’ll share research on magnesium absorption, with a focus on magnesium citrate.

Below, you’ll find:

  • A study on the absorbability of magnesium supplements (summary)
  • Dr. Alison Smith’s insights on the study and how it challenges myths about magnesium
  • A scientific white paper summarizing what published research says about magnesium absorption
  • Dr. Alison Smith’s explanation of the white paper 
  • An explainer article by Natural Vitality on why Natural Calm uses magnesium citrate

But first, let’s cover the basics of magnesium absorption and why it matters.

Why Magnesium Absorption Matters

The Most Effective & Absorbable Magnesium Supplement

Magnesium is one of the most critical dietary nutrients, required for hundreds of processes in your body. This hard-working mineral helps with:

The trouble is, most people simply don’t eat enough magnesium-rich foods! It’s hard. You’d have to eat approximately 12 cups of raw spinach to get the low end of your daily requirement: about 300 mg.

Depending on your lifestyle, you may need more magnesium. Stress, sugar, sweat, caffeine, alcohol, and many medications drain magnesium stores.

But if you choose to supplement with magnesium, which type should you choose?

Magnesium comes in a dizzying variety of forms. There are tablets, capsules, gels, powders, and even transdermal magnesium.

To make matters more confusing, many brands slap a “more absorbable” claim on their label. But aren’t all supplements absorbable?

Unfortunately, no. There are wide differences in the absorbability of all kinds of supplements.

Just because a label says “more absorbable” doesn’t necessarily mean it is. Absorbability is one of those terms that is not tightly regulated. And yet, absorption is important.

A supplement that can be absorbed is ‘bioavailable’. That means it can reach the bloodstream and go to work across the cells and systems of your body.

Here’s a key principle to remember: If a magnesium supplement dissolves well, it can be absorbed.1

That’s why many experts suggest magnesium drinks over magnesium tablets.

As you’ll learn from the white paper, below, the most soluble (or dissolvable) types of magnesium are organic magnesium salts and chelates.2, 3, 4

That’s not very helpful when you’re skimming labels, granted. To simplify your search for absorbable magnesium salts and chelates, look for forms like these:

Steer clear of magnesium oxide, though. It’s a common form because magnesium oxide is inexpensive, but it isn’t very absorbable.2, 3, 4

Next to reviewing the science, the best way to tell if your magnesium is working is by paying attention to how you feel.

Are you less tense and irritable? Do you sleep better at night? Are you more regular? (Yes, that’s a sign!) If you have pain, is it improving?

If you can say “yes” to any of these, chances are, your magnesium supplement is working.

These are the results users of Natural Calm regularly report, and more. Check out their stories on our testimonials page.

Now, on with the scientific articles on magnesium absorption.

 

Natural Calm’s Magnesium Citrate Absorption Study

Magnesium absorption research

The following is a summary of a study using Natural Calm magnesium. This randomized, double-blind, placebo-controlled, crossover trial compared the bioavailability of Natural Calm magnesium with three other popular magnesium supplements available in Canada.

Study Background

Natural Calm is a magnesium citrate supplement, made by combining magnesium carbonate and citric acid. When these ingredients are mixed in liquid, the magnesium carbonate converts to magnesium citrate.

It is widely held that magnesium citrate is three times better absorbed than magnesium oxide.

However, at Natural Calm, we wanted to demonstrate the efficacy of our magnesium citrate formula against other leading magnesium supplements of high quality. Specifically, we wanted to demonstrate the absorbability of Natural Calm against other magnesium citrate brands, and against magnesium bisglycinate brands that do not contain magnesium citrate.

In 2016, Natural Calm Canada contracted with Nutrasource, a full-service contract research organization (CRO) specializing in clinical trials and product testing for the natural health industry, to compare magnesium absorption from four brands of magnesium supplements.

The results were released by Nutrasource in September 2017, and presented at the Canadian Health Food Association by Dr. Alison Smith.  

Study Methodology

Nutrasource conducted a 10-week, randomized, double-blind, crossover study including 12 healthy, postmenopausal women, randomized into four different treatment sequences. All subjects took 150 mg of the four magnesium brands or a placebo; however, the sequence of treatment varied between subjects.

Study Duration: June 2016 – September 2017. Each subject visited the clinic 27 times plus two screening visits.

Supplement brands included in the study:

Natural Calm Magnesium carbonate powder with citric acid that converts to magnesium citrate once dissolved in hot water
Magnesium Glycinate 1. Magnesium bisglycinate powder dissolved in water
Magnesium Glycinate 2. Magnesium bisglycinate powder dissolved in water
Magnesium Citrate 2. Magnesium citrate powder in a capsule
Placebo Hypromellose and rice flour contained in a capsule. One capsule contained an estimated 0.26 mg of magnesium.

Primary Measurement: The concentration of magnesium in the blood serum and urine between 0-8 hours following supplement ingestion. (For information on the rationale for measuring magnesium absorption via blood serum and urine tests, see the white paper below.)

Secondary Measurements: The concentration of magnesium in the blood serum and urine between 0-10 hours, 0-12 hours, 0-24 hours (urine only), as well as maximum concentration (Cmax) and time to maximum concentration (Tmax) of magnesium in the blood serum and urine.

Magnesium Absorption Study Results

10 subjects completed the study and the following results were found.

  1. For the primary measurement, between 0-8 hours, Natural Calm magnesium citrate significantly increased magnesium concentration in both the blood serum and urine, compared to taking a placebo. The magnesium bisglycinate supplements and the magnesium citrate capsule did not significantly increase magnesium concentration in either the blood serum or urine during this time period.
  1. For the secondary measurement, between 0-12 hours,  Natural Calm magnesium citrate significantly increased magnesium concentration in the urine compared to magnesium bisglycinate supplement.
  1. The maximum concentration of magnesium in the urine (Cmax) was measured after collecting urine over the course of 24 hours. Cmax was a secondary study measure. Results showed the magnesium citrate capsule to significantly increase magnesium concentration in the urine compared to magnesium bisglycinate supplement.

Conclusions: Natural Calm Magnesium is Proven More Absorbable

According to the primary measurement, Natural Calm magnesium citrate significantly increases the bioavailability of magnesium in the human body compared to magnesium glycinate competitors.

Overall, the statistical tests with a significant result showed that the magnesium citrate supplements from Natural Calm outperformed both magnesium bisglycinate supplements.

Postscript Notes

For the full study results, please contact info@naturalcalm.ca.

We acknowledge that the quality of magnesium glycinate used in the tested products may be a factor, despite that these are two leading magnesium glycinate brands. In 2017, it was revealed that a number of Canadian magnesium glycinate brands contained undisclosed magnesium oxide, a less absorbable form. This may have influenced the study results.

Myths Versus Facts About Magnesium Citrate Absorption 

best absorbed magnesium type

The following is an article by Dr. Alison Smith, Ph.D., Neuroscience. Below, Dr. Smith explains what the magnesium citrate absorption study means, and how it challenges key myths in the supplement industry.

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 (above) 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 my interpretation of 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 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 About Magnesium Absorption?

To evaluate the claims in the quotes above, Natural Calm Canada took two steps.

  1. They commissioned a full clinical study on magnesium absorption, comparing Natural Calm against three other popular magnesium brands in Canada, including the two brands quoted above.
  2. 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 and is included below. You can also read my summary of the literature review on magnesium absorption below.

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 understand 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. Magnesium bisglycinate powder 1
  3. Magnesium bisglycinate powder 2
  4. 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
  • Magnesium glycinate powder 1
  • Magnesium glycinate powder 2
  • 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:

  1. 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]
    1. Quamme GA. 1993 Magnesium homeostasis and renal magnesium handling.  Miner Electrolyte Metab.;19: 218-255
    2. Kayne LH, Lee DB. 1993 Intestinal magnesium absorption. Miner Electrolyte Metab.;19:210-217
    3. Siener R, Jahnen A, Hesse, A. 2011 Bioavailability of magnesium from different pharmaceutical formulations. Urol Res.;39:123-127
    4. Niazi SK. Handbook of Bioequivalence Testing, Second Edition (Drugs and the Pharmaceutical Sciences). CRC Press.  Taylor and Francis Group. Boca Raton Florida. 2015.
  2. Blood serum concentration of magnesium is not a perfect measure; however, it is used regularly in peer-reviewed publications. (Please visit PubMed, 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. [8]e) European Medicines Agency.  Guideline on the Investigation of Bioequivalence. London, 20 January 2010.
  3. 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 did we learn from clinically comparing Natural Calm magnesium citrate absorption against three 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, or the magnesium citrate capsules, 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 Magnesium bisglycinate 2

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 magnesium citrate capsule to significantly increase magnesium concentration in the urine compared to magnesium bisglycinate 2 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 magnesium citrate capsule was significantly higher than taking the magnesium bisglycinate powder.

Natural Calm is Proven More Absorbable

Overall, the results showed that the magnesium citrate supplements from Natural Calm and Natural Factors outperformed both magnesium bisglycinate supplements.

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.

 

Magnesium Citrate Absorption Compared to Other Forms of Magnesium

Magnesium (citrate) absorption & bioavailability

To better understand magnesium absorption, Natural Calm engaged scientific partners to prepare a review of the scientific literature. The following is a white paper prepared by Dr. Jon-Paul Powers, PhD, Microbiology, Partner and Scientific Advisor, Gowling GWL

Despite its essential role in human health, many modern diets are deficient in magnesium. As a result, many consumers select magnesium supplements as a convenient way to meet their daily requirements. Supplements contain a variety of inorganic and organic forms of magnesium, whose effectiveness may depend upon their bioavailability in the body. Magnesium citrate, and other organic magnesium salts, have demonstrated superior bioavailability to inorganic magnesium salts. This makes magnesium citrate an effective source material for oral magnesium supplementation.

Role and Benefits of Magnesium

Magnesium is an essential nutrient for the human body and is known to be involved in more than 300 biochemical reactions affecting key processes such as energy production, bone development, maintaining electrolyte balance, muscle and heart function, as well as protein, DNA, and RNA synthesis. (1,2) Magnesium also plays a role in the transport of sodium and potassium ions across cellular membranes. (3) Recently, magnesium has also been demonstrated to improve bowel movement and frequency thereby reducing functional constipation. (4,5) More than half of the body’s 20-28 g magnesium store is present in bones with the remainder residing in the soft tissues and, to a very minor extent (<1%), in the blood. (6,7)

Dietary Magnesium Requirements

Adults require approximately 310-420 mg of magnesium daily, and deficiency may lead to irritability, muscle weakness, and irregular heartbeat. (8) Most dietary magnesium typically comes from sources such as fruits, vegetables, leafy greens, and seeds and grains. While magnesium is present in food sources, recent Health Canada findings suggest that many adults have an inadequate dietary intake of magnesium. (9) Due to deficiencies in modern diets, many consumers select magnesium supplements as a convenient way to meet their daily requirements.

Magnesium Supplements

Oral magnesium supplements are available in a variety of formats with powders and capsules being the most common. The magnesium contained in these supplements may be from a variety of source materials or forms, generally grouped as follows:

• Inorganic magnesium salts (such as oxides, carbonates, chlorides and hydroxides);
• Organic magnesium salts (such as citrates, lactates, and gluconates); and
• Magnesium complexes or chelates (such as amino acid chelates).

From a formulation or manufacturing perspective, the selection of a specific magnesium source material may be due to a variety of reasons including, but not limited to, cost, solubility and available capsule space. From a biological perspective, it should be noted that source material ultimately affects magnesium absorption and bioavailability.

Magnesium Absorption

The absorption of magnesium from oral supplementation occurs primarily in the small intestine with the majority of uptake occurring in the distal jejunum and the ileum.(10,11) Once dissolved in the gastric fluid, magnesium salts dissociate, freeing the ionic magnesium. The majority of the magnesium ions in the intestinal tract are taken up through passive processes mediated by electrochemical gradients and solvent drag, but some uptake occurs via an active transport system. Once absorbed by the intestine, magnesium ions enter the bloodstream for transport to other tissues and organs.

Measuring magnesium absorption

There are two common methods used to estimate absorption/bioavailability of ingested magnesium. The most widely available and practical way to determine intestinal magnesium absorption is by measuring blood serum magnesium levels.(12,13) In serum magnesium analysis, acute changes in the magnesium status of an individual are detected by measuring the concentration of total serum magnesium following magnesium intake. Since serum magnesium does not correlate well with tissue pools of magnesium, this test is considered a poor predictor of intracellular or body magnesium content; however, it remains effective and reliable for measuring rapid extracellular changes in magnesium levels, and to assess intestinal absorption following an oral load of magnesium. (14,15)

Urinary analysis is another common method for assessing magnesium absorption. Once magnesium levels exceed a critical threshold in the kidney, the excess magnesium is excreted in the urine. (16)

In general, the assumption is that the uptake and release of magnesium are in balance;(17) thus, by determining the concentration of magnesium excreted in the urine, one can estimate the amount of magnesium absorbed by the intestine. Drawbacks to this method of analysis are that test subjects must not be magnesium depleted, and timing of the analysis is critical.

Other, less common, proxies for magnesium absorption include measuring an increase in salivary or erythrocyte magnesium concentrations. (18) Stable isotopes of magnesium have also been used to track the absorption of magnesium by the body. (19)

Magnesium Bioavailability

The solubility of minerals in the digestive tract is a major factor driving their uptake. (20) Because much of the absorption of magnesium is via passive transport, the greater the solubility of magnesium salt or complex that is in the gut, the greater the potential for magnesium ion dissociation and subsequent availability for uptake into the intestine. Thus, the solubility of the magnesium supplement factors in its overall bioavailability.

Organic magnesium salts, such as magnesium citrate, are, in general, more soluble than inorganic magnesium salts. (21) The enhanced solubility leads to a greater concentration of magnesium ions in the intestinal tract. Because of this, supplements containing the highly soluble organic salt forms may be more absorbable by the body (and, therefore, more bioavailable) than inorganic salt forms. Indeed, in vitro and clinical studies have demonstrated the superior solubility and bioavailability of oral organic magnesium salts compared to the representative inorganic form, magnesium oxide. (22,23,24) While most studies to date have used urinary magnesium levels as a measure of bioavailability, Wilimzig et al. (1996) further demonstrated that administration of oral magnesium citrate produced a direct increase in plasma magnesium concentrations in healthy volunteers. (25)

Magnesium citrate is regarded as a highly soluble and readily bioavailable form of magnesium. (26) Studies in simulated gastric fluid demonstrate that magnesium citrate remains in solution even as pH increases.(27) This is an important characteristic since the pH of the intestine increases as it progresses distally. The solubility of magnesium citrate in alkaline environments may enhance bioavailability by increasing the availability of free magnesium ions for passive uptake along the intestinal tract. This means that magnesium ions may remain bioavailable further along the intestinal tract, without the need for additional buffers, allowing more opportunity for transport through cellular membranes. Numerous in vitro studies have demonstrated the superior absorption of organic magnesium salts, including magnesium citrate, in comparison with inorganic salts. (28)

Furthermore, magnesium citrate was found to be both more soluble in simulated gastric acid, and more intestinally absorbable than magnesium oxide, as determined by urinary magnesium excretion analysis in healthy volunteers.(29) The results of these parallel in vitro and in vivo tests suggest that magnesium citrate’s increased bioavailability relative to magnesium oxide may be a result of its enhanced solubility in the intestinal tract.

Recently, magnesium in the form of amino acid chelates such as aspartate and bisglycinate (aka diglycinate) have been the focus of advertising campaigns. While these sources have been marketed as being more bioavailable than other common inorganic and organic forms, there is a lack of published data supporting these claims.

There is only one study by Schuette et al. that demonstrated that magnesium bisglycinate is more absorbable than magnesium oxide in a subgroup of subjects who had undergone ileal resection.[30] Furthermore, a detailed review of the bioavailability and pharmacokinetics of magnesium shows little, if any, difference between magnesium forms generally regarded as bioavailable, for example magnesium citrate and magnesium glycinate.[31]

In perhaps the best study design to date, the bioavailability of magnesium citrate was found to be superior to both magnesium oxide and a magnesium amino acid chelate. Walker et al. (2003) conducted a parallel intervention study to compare the relative absorbability and bioequivalence of three forms of magnesium (oxide, citrate and amino acid chelate) under acute (24 h) and chronic (60 days) administration of an oral daily dosage. (32)

Subjects were generally healthy and free of conditions or activities known to affect magnesium metabolism and were administered cellulose or sorbitol placebo or 300 mg elemental magnesium per day from one of the following sources: magnesium amino acid chelate, magnesium citrate, magnesium oxide.

Treatment effects were assessed via urinary magnesium excretion, plasma magnesium concentration, erythrocyte magnesium concentration or salivary magnesium concentration.

Chronic supplementation with organic forms of magnesium (magnesium citrate and magnesium amino acid chelate) resulted in a significant increase in urinary magnesium excretion compared to either placebo or magnesium oxide, which is an indirect measure of the increased bioavailability of magnesium citrate.(33)

As further evidence of the increased bioavailability of magnesium citrate both mean plasma and salivary magnesium concentrations were assayed. Only magnesium citrate was found to produce statistically significant increases compared to all other groups following chronic administration. (34)

While this study was designed to determine the differences in magnesium supplementation compared to placebo, it does suggest that supplementation with magnesium citrate may be superior to supplementation with both magnesium oxide and amino acid chelate forms (e.g. bisglycinate, etc.).

Conclusion

Organic magnesium salts, such as magnesium citrate, are highly soluble in the intestinal tract, which leads to high concentrations of ionic magnesium that can be absorbed by the body. In addition, the enhanced bioavailability of magnesium citrate compared with inorganic magnesium salts (oxides, carbonates, chlorides and hydroxides) is well supported. Furthermore, the above-mentioned clinical trial has demonstrated that magnesium citrate absorption is equal to or greater than that of amino acid chelates like magnesium bisglycinates. Therefore, due to its solubility, and superior bioavailability, magnesium citrate is a highly effective form of magnesium supplementation.

See also our blog post on the topic: Are You Being Misled About Magnesium?

Magnesium Citrate Absorption: What the Research Says

research magnesium citrate and glycinate

In this explainer post, Dr. Alison Smith breaks down the findings from Dr. Powers’ white paper above.

Natural Calm has been on a quest to publish the truth about magnesium absorption.

To get an unbiased, authoritative perspective, 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 happens to also be a former unit head and assessment officer for the National Health Products Directorate of Health Canada. Needless to say, he’s a highly qualified scientific expert capable of illuminating the truth about magnesium supplements.

Understanding the Different Types of Magnesium Supplements

To understand Dr. Powers’ review of the science above, you need to understand the forms in which magnesium supplements are available.

Magnesium supplements contain a variety of different magnesium salts. There isn’t just one type of magnesium salt on the market.

In general, magnesium salts are classified into two major types: organic and inorganic.

Organic magnesium salts are created in a laboratory by combining an inorganic magnesium salt with either an acid or an amino acid (a protein). For example, magnesium citrate is created by combining magnesium with citric acid, and magnesium glycinate is created by combining magnesium with the amino acid, glycine.

Inorganic magnesium salts are naturally derived from harvested earth and rock sources.

** Important to know ** — Natural Calm contains magnesium citrate. Magnesium citrate is created when you dissolve powdered magnesium carbonate (a mineral sourced from deep in the ocean) with citric acid in water. The reaction takes place quickly when dissolved in hot water, and more slowly in cooler water.

Organic Magnesium Salts Commonly Used in Supplements

Magnesium that contains an acid:

  • Mg Citrate (Natural Calm)
  • Mg Gluconate
  • Mg Malate
  • Mg Orotate
  • Mg Ascorbate
  • Mg Lactate
  • Mg Fumerate

Magnesium that contains an amino acid:

  • Mg Glycinate
  • Mg Pidolate
  • Mg Taurate
  • Mg Glutamate
  • Mg Aspartate
  • Mg Threonate

Inorganic Magnesium Salts Commonly Used in Supplements

  • Mg Chloride
  • Mg Carbonate
  • Mg Oxide
  • Mg Sulfate

Ok, now that we have the Magnesium 101 covered, let’s do a re-cap on what the published research really says – that is, the peer-reviewed research available in scientific journals. I’ll then move on to the new results from the clinical trial.

What the Published Research Says About Magnesium Absorption

To summarize Dr. Power’s review of the literature:

  1. There has 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.
  2. Which type of magnesium salt is the best: organic or inorganic? Well, research tells us that organic magnesium salts –– the ones that contain an acid or an amino acid –– are more soluble, absorbable, and bioavailable than inorganic magnesium salts. [1] Ranade and Somberg (2001). Am J Ther. 8(5), 345-57.
  3. Magnesium citrate can withstand drastic acidic changes in the gut; therefore, giving it more time to be absorbed and to become bioavailable. [2] Lindberg et al. (1990). J Amer Col Nutr. 9(1), 48-55.
  4. Magnesium citrate is more absorbable and bioavailable than inorganic magnesium oxide. Lindberg et al. (1990) J Amer Col Nutr 9(1), 48-55.
  5. Magnesium citrate is more absorbable and bioavailable than an amino acid chelate against which it was tested in a study. (Magnesium glycinate is an amino acid chelate, so this is indirect evidence that magnesium citrate might be more effective than magnesium glycinate, but we need more research…and that’s coming up. Stay tuned!) [3] Walker et al. (2003) Magnes Res 6(3), 183-91.

What Does This Mean About the Difference Between Magnesium Citrate and Magnesium Glycinate?

So, what conclusions can we come to about magnesium absorption, based only on the scientific literature?

  1. Overall, there is very little research comparing magnesium salts against each other. This is a problem, and it contributes to the issue of misinformation and bogus claims.
  2. We definitely know that organic magnesium salts are more effective than inorganic magnesium salts, but when it comes to comparing ALL of the organic magnesium salts against each other, we simply do not have enough published research to say which is more effective.
  3. Magnesium glycinate isn’t any more effective than other organic magnesium salts including magnesium citrate.
  4. Magnesium citrate can significantly absorb into the bloodstream to become bioavailable. [2,3]e4 Lindberg et al. (1990). J Amer Col Nutr. 9(1), 48-55; Walker et al. (2003) Magnes Res 6(3), 183-91.
  5. The claims about magnesium glycinate are not based on science and are therefore bogus information.

We know this much from the existing, peer-reviewed, published science.

Why Does Natural Calm Use Magnesium Citrate?

Natural Calm Magnesium Citrate Flavours e1640622857389

This article is adapted from Natural Vitality, with permission. Natural Vitality is the brand behind Natural Calm in the US, and Natural Calm Canada is their sole Canadian distributor.

There’s no better time to start taking a more proactive approach to everyday wellness. You might be thinking of eating better, exercising more, and making simple lifestyle changes to support optimal health—and one of those changes is adding more magnesium to their daily diet.

Magnesium is an essential mineral involved in over 300 cellular processes, including those responsible for protein synthesis and ATP production, but many Canadians still fall short of consuming the recommended daily amount.

Taking a daily supplement can help boost your magnesium intake, but it is important to make sure the supplement you choose is fully absorbed by your body so you get the most benefit.

Absorbability is where magnesium citrate shines

First, a little science: Magnesium supplements come in the form of compounds. The magnesium ion (Mg2+) is combined with a salt, an acid, or an amino acid chelate to keep the mineral ion in a stable form that is suitable for consumption.

Magnesium citrate combines the salt element of magnesium with citric acid, resulting in a highly absorbable form of magnesium. With most magnesium supplements, the body is only able to absorb and assimilate a small percentage of the magnesium, but in the form of a mineral citrate, the body is able to absorb a much greater amount.

Why does magnesium absorbability matter?

If you’re taking a daily magnesium supplement but your body can’t easily take in and use the magnesium compound, you’ll miss out on all of the health-promoting benefits. On the other hand, if it’s readily absorbed and usable by your body—what scientists call bioavailable—then you’re in luck.

While not all magnesium compounds are created equal, magnesium citrate and glycinate are two of the better-absorbed forms of magnesium.

What types of magnesium does Natural Calm Canada use?

Most Natural Calm drink powders contain magnesium carbonate along with citric acid; this forms a magnesium citrate solution when combined with water. The reaction will occur immediately in hot water, and when the fizzing subsides it means the product is converted into magnesium citrate.

f you prefer cold water, the process may take up to 15 minutes. Either way, the final product, once dissolved, is ready to be absorbed and utilized by your body.

Natural Calm gummies contain magnesium citrate as well.

Natural Calm also offers supplements with a combination of magnesium citrate and magnesium glycinate. 

Ultimately, what matters is whether or not your supplement is able to get the magnesium to your cells, where it’s needed.

Magnesium citrate and glycinate are not only well absorbed, but they are also highly bioavailable.

References: All Articles

This post is comprised of multiple separate articles. We’ve included the references for each here, in order.

References: Why Magnesium Absorption Matters

  1. Coudray, C., Rambeau, M., Feillet-Coudray, C., Gueux, E., Tressol, J. C., Mazur, A., & Rayssiguier, Y. (2005). Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnesium research, 18(4), 215–223.
  2. Lindberg, J. S., Zobitz, M. M., Poindexter, J. R., & Pak, C. Y. (1990). Magnesium bioavailability from magnesium citrate and magnesium oxide. Journal of the American College of Nutrition, 9(1), 48–55. https://doi.org/10.1080/07315724.1990.10720349
  3. Firoz, M., & Graber, M. (2001). Bioavailability of US commercial magnesium preparations. Magnesium research, 14(4), 257–262.
  4. Coudray, C., Rambeau, M., Feillet-Coudray, C., Gueux, E., Tressol, J. C., Mazur, A., & Rayssiguier, Y. (2005). Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnesium research, 18(4), 215–223.
  5. Nutrasource, 2017 (Guelph, Ontario). Summary available at https://naturalcalm.ca/is-your-magnesium-supplement-clinically-proven-more-absorbable/

References: Myths Versus Facts About Magnesium Absorption

  1. Ranade, V. V., & Somberg, J. C. (2001). Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. American journal of therapeutics, 8(5), 345–357. https://doi.org/10.1097/00045391-200109000-00008 [PubMed]
  2. Lindberg, J. S., Zobitz, M. M., Poindexter, J. R., & Pak, C. Y. (1990). Magnesium bioavailability from magnesium citrate and magnesium oxide. Journal of the American College of Nutrition, 9(1), 48–55. https://doi.org/10.1080/07315724.1990.10720349 [PubMed]
  3. Walker, A. F., Marakis, G., Christie, S., & Byng, M. (2003). Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnesium research, 16(3), 183–191. [PubMed]
  4. Quamme G. A. (1993). Magnesium homeostasis and renal magnesium handling. Mineral and electrolyte metabolism, 19(4-5), 218–225. [PubMed]
  5. Kayne LH, Lee DB. Intestinal magnesium absorption. Mineral and Electrolyte Metabolism. 1993 ;19(4-5):210-217. [EuropePMC]
  6. Siener, R., Jahnen, A., & Hesse, A. (2011). Bioavailability of magnesium from different pharmaceutical formulations. Urological research, 39(2), 123–127. https://doi.org/10.1007/s00240-010-0309-y [PubMed]
  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.

References: Magnesium Citrate Absorption Compared to Other Forms of Magnesium

1 World Health Organization, available at: https://www.fao.org/DoCREP/004/Y2809E/y2809e0k.htm

2 Health Canada, available at: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=multi_vitmin_suppl&lang=eng

3 Bara et al. Magnesium Res 1993;6(2):167-177

4 Dupont et al. Clin Gastroenterol Hepatol 2014;12(8):1280-7

5 Bothe et al. Eur J Nutr 2015; Nov.18 ahead of print.

6 Schaafsma. Eur J Clin Nutr 1997;51(1):13-16

7 Benech and Grognet. Magnesium Res 1995;8(3):277-284

8 Mayo Clinic, available at: https://www.mayoclinic.org/drugs-supplements/magnesium-supplement-oral-route-parenteral-route/description/drg-200707309 Health Canada, available at: https://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php

9 Health Canada, available at: https://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php

10 Coudray et al. Magnesium Res 2005;18(4):215-23

11 Ranade and Somberg. Am J Therapeutics 2001;8:345-357

12 Ranade and Somberg. Am J Therapeutics 2001;8:345-357

13 Johen-Dechent and Ketteler. Clin Kidney 2012;5(1):i3-i14

14 Johen-Dechent and Ketteler. Clin Kidney 2012;5(1):i3-i14

15 Elin. Dis Mon 1988;34(4):161-218

16 Ranade and Somberg. Am J Therapeutics 2001;8:345-357

17 Bohmer et al. Magnesium Trace Elem 1990;9:272-278

18 Walker et al. Magnes Res 2003;6(3):183-91

19 Schuette et al. JPEN J Parenter Enteral Nutr 1994;18(5):430-435

20 Coudray et al. Magnesium Research 2005;18(4):215-23

21 Siebrecht, S. OM & Ernährung 2013;144:2-16

22 Lindberg et al. J Amer Col of Nutrition 1990;9(1):48-55

23 Firoz and Graber. Magnesium Research 2001;14(4):257-262

24 Coudray et al. Magnesium Research 2005;18(4):215-23

25 Wilimzig et al. Euro J Clin Pharmacol 1996;49:317-323

26 Ranade and Somberg. Am J Ther 2001;8:345-357

27 Lindberg et al. J Amer Col Nutr 1990;9(1):48-5528

28 Couday et al. Magnesium Res 2005;18(4):215-23

29 Lindberg et al. J Amer Col Nutr 1990;9(1):48-55

30 Schuette et al. J Parenter Enteral Nutr 1994;18:430-435

31 Ranade and Somberg. Am J Ther 2001;8:345-357

32 Walker et al. Magnes Res 2003;6(3):183-91

33 Walker et al. Magnes Res 2003;6(3):183-91

34 Walker et al. Magnes Res 2003;6(3):183-91

References: Why Does Natural Calm Use Magnesium Citrate

  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.

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