Magnesium l-threonate is a variety of magnesium suggested in a few small animal studies to have better uptake into the brain and hence increased cognitive effects compared to more common forms of magnesium supplements like magnesium citrate. I am interested in magnesium supplementation in general, but magnesium l-threonate is far more expensive than magnesium citrate (likely due to its status as a patented formulation, controlled by AIDP Inc & Magceutics), and animal studies are a thin reed to rely on, so I went looking for human trials. In January 2012, the official Magtein website stated that:

A human study for memory and cognitive function has just started at University of Southern California, Department of Psychology, with a leading expert in cognitive health. It is a double-blind, placebo controlled study with 40 individuals. Preliminary results will be available by mid 2012.

In June 2013, I noted that no publications or results had been posted, and the page now read just:

For the second study, a double-blind, placebo-controlled human study with a top researcher at the University in California has been started to verify the functions of Magtein on memory and cognitive functions observed in animals as well as reported by individuals who took this product.

So on 17 June 2013, I emailed customercare@aidp.com asking whether there was any information or preprints of this study, or the name of the lead researcher so I could ask them instead; their representative Kathy Lund replied that

This study is still pending.

Since the study was supposed to have already been started all the way back in January 2012, and results be available within months, I asked what 'pending' meant, exactly, and Lund quickly clarified:

The study is still in the design phase. Another human clinical through a CRO has begun. Results are likely due early in 2014.

It seemed odd that it would take more than a year and a half to design what should be a straightforward experiment (do a within-subject design of a few standard WM tasks like digit span, for example), but OK. (I was also concerned by the use of a CRO, since 'incentives matter', but that's a much lesser issue.) I would look forward to the CRO's results, and perhaps the USC study would also finally get underway as well.

In late 2014, there were still no published human studies. So on 12 January 2015, I emailed Lund again:

Any news? I haven't seen anything pop up about a human magtein trial in Google Scholar: http://scholar.google.com/scholar?as_ylo=2014&q=magnesium+magtein&hl=en&as_sdt=0,21

No reply.

On 18 June 2015, I emailed Lund again:

Ping? You said the CRO's study had begun already, so there should have been results a long time ago. Should people be inferring that the results were embarrassing and writeups have been dropped?

Still no reply.

Checking right now on 20 October 2015, Pubmed still records no human trials; whilea search for magnesium l-threonate publications involving humans (http://www.ncbi.nlm.nih.gov/pubmed/?term=((%22magnesium%22%5BMeSH+Terms%5D+OR+%22magnesium%22%5BAll+Fields%5D)+AND+l-threonate%5BAll+Fields%5D)+AND+%22humans%22%5BMeSH+Terms%5D) turns up 3 studies, they are 2 mice studies and 1 editorial. None could be the CRO study. This means that it is now somewhere around a year and a half overdue; further, the Magtein website science now says even less about any human experiments, with a single sentence reading:

Human studies are currently under development.

Between the total absence of publications and the steady deletion of details from their science page, it doesn't look like the USC or CRO studies will be published anytime soon.

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So to summarize, it seems that there are now possibly two (or more!) missing human trials on magnesium l-threonate: the USC study, which may or may not have made it to a pilot or full study, and the CRO, where Lund stated that the trial had definitely begun and its nonappearance is definite.

What are the implications? (And why am I quoting private emails, albeit ones sent in an official capacity, in public?) The most obvious and common reason for nonpublication of results is that they were embarrassing and did not turn in the dramatic effect sizes seen in the small animal studies and everyone involved either lost interest in the unsexy results or decided to not publicize the results. If this is the case, then this is a serious blow to the case for magnesium l-threonate: whatever study may come out in the future, we must suspect that it is an overestimate of the benefit of magnesium l-threonate, and any attempt to meta-analyze will need to adjust for the known publication bias at play.

Speaking for myself, the case for magnesium l-threonate was always more than a little dubious because the prior odds are against any new supplement turning out to be useful, the support for l-threonate rests on the dubious base of animal studies (known to be of low quality and to poorly predict human results), and the sheer expense makes it unlikely for l-threonate to be cost-effective, which are the reasons that, after trying out 1 container of the LEF formulation, I moved on to experimenting with the far cheaper magnesium citrate. But even if positive human studies come out in the future, it will be hard for me to trust them given my experience over the past 3-4 years patiently waiting for these promised human trials to come out.