My magnesium story – Magnesium in Pregnancy
The effect of magnesium on premature labour was discovered by accident. Spätling conducted many studies to classify the finding, including a prospektiv randomized double-blind study. (Images for this article in the German version)
Gabi’s first pregnancy
If you curiously open a door, you will find many closed doors behind it that need to be opened again. That was probably one of those moments when my wife Gabi was pregnant with our Julia.
At perhaps 28 weeks pregnant, Gabi suffered from contractions one morning. At that time, no distinction was made between contractions and contractions of the uterus. So we went to see Hans-Jürgen Holländer, who was the head of the women’s clinic at St. Johannes Hospital in Duisburg-Hamborn in 1974. (For the sake of readability, I have refrained from mentioning academic degrees in this article). I had just completed my medical internship in internal medicine and surgery in Hamborn before returning to Marburg for gynecology. Hans-Jürgen Holländer had just completed his atlas on the first clinically practicable ultrasound device, the „Vidoson“ from Siemens. It was the beginning of measuring structures in the „snow flurry“ of signals. There was also a first cardiotocography device. It took a long time to find the heart signal. In addition, a bulky contraction transducer was fixed to the abdomen with coarse straps. The whole manipulation of the abdomen also triggered contractions, at least in my Gabi.
Dangerous therapy for premature labor
There is now a completely new drug that could be used to inhibit contractions. It was called TH1165a and was produced by Böhringer-Ingelheim. It was derived from adrenaline and also had corresponding effects and, of course, side effects. First and foremost, palpitations. TH1165a had not yet been properly approved. Otherwise it would have had a proper name.
How was dosing done? There were no electronic drip counters yet. So they counted the drops per minute and regulated, for example, eight drops per minute with a wheel that squeezed the infusion tube and thus impeded the flow. The nurse came every hour to check. Day and night. One night Gabi was lying on the arm to which the infusion was attached and the medication was flowing very slowly. The night nurse adjusted the dial until eight drops per minute flowed again. Gabi didn’t always sleep on the same side either, so she turned and released the flow. In a very short time, the bottle was empty and Gabi was in a very bad way. I only learned later that you can die from something like this. Long after the birth, she still had periods of slow heartbeat and a feeling as if her tongue was falling down her throat. Thank God she survived. She would have sat next to the crib, terrified that she would die and that Julia would have to grow up without a mother. She had these infusions for eight weeks . From week to week, the hair[1] all over her skin grew longer and longer. She looked like a monkey.
But for me it was a stimulus not to accept every therapy. After all, we doctors had the goal of curing patients, not killing them.
Our Julia was born at 38 weeks and was a little delicate but healthy.
Gabi’s second pregnancy
After my time as a medical assistant, I got a position as an assistant at the women’s clinic in Marburg. So we moved from Duisburg to Marburg and „practiced“ for a second pregnancy. No sooner had I started the job than I was called up for military service. I lodged an objection. In a temporary injunction, the court rated the state’s interest in my person higher than my own interest in an impeded academic career. Four weeks after the end of my military service, the same ruling was issued following my appeal against my conscription. With some despair, I tried to continue my perfusion experiments, which I had previously carried out on „human and bovine“ ovaries, with rat placentas. I still had access to the laboratory and animal barn and I was also allowed to keep my office in the women’s clinic. For the future, I learned from the rat experiments during this time how not to do experimental science
After completing my military service, I was able to return to work in the women’s clinic straight away. Gabi and I made the plan for a second pregnancy a reality. Premature „contractions“ started again at around 28 weeks of pregnancy, and again we were given the betamimetic to inhibit contractions, which had been approved in the meantime and was now called Fenoterol by its generic name and Partusisten by its trade name. Again the hair sprouted all over the skin. This was the starting signal for the search for the cause of the increased hair growth. The Partusisten manufacturing company financed the analyses of android hormones in all women who also showed increased hair growth when taking Partusisten (see footnote 1). Gabi’s haemoglobin level also dropped considerably. And as I had the same blood group and she didn’t want to go to hospital (and couldn’t because of Julia), I transfused my blood at home. But she had to go to hospital after all, because her waters broke at around 30 weeks and the amniotic fluid ran down her legs in the middle of the living room. As she had to be transported lying down , the paramedics came and took Gabi to the Marburg Women’s Clinic. I still remember today that Mrs. Schulze, who was on senior physician duty, reported at the morning report. „Yesterday evening, Mrs. Spätling came with an alleged rupture of the membranes.“ Sometimes no amniotic fluid continues to drain when the amniotic sac breaks again and the membranes overlap and seal the tear in the amniotic sac again. Or all the amniotic fluid has drained away so that no more amniotic fluid can be observed. It was not yet possible to carry out an ultrasound examination at this time. I was so annoyed by this senior physician’s statement. A patient is not believed. And as if I, as an obstetrics and gynecology resident, couldn’t tell the difference between amniotic fluid and urine. The color and smell are clear.
Who was going to look after Julia now? Her parents and parents-in-law were in Duisburg and unavailable. So I took Julia to our friends Karla and Uli Baum in Ingelfingen. They had Christoph there, who was almost the same age. Karla and Uli were happy to take Julia. Now Gabi was receiving Partusisten intravenously again, but this time with an electronic drip counter. Then Christmas came. I picked Julia up in Ingelfingen and took her to my office, where I had already decorated a tree. Then I picked Gabi up from her hospital room on a stretcher and we celebrated Christmas 1976 together.
No sign of magnesium yet.
Magnesium and Gabi’s third pregnancy
We actually wanted to have a third child. But with this medical history, we don’t have the courage to go through with it. Coincidences can sometimes help. Gabi’s sister Christiane became pregnant for her teaching exams. We were able to motivate her and her husband to move to Wenkbach for the duration of her pregnancy. We had moved to the suburbs of Marburg in the meantime and had plenty of space there. So we were able to think about the realization of the third pregnancy. In the very likely event of complications arising again, we then had someone who could look after Julia and Caroline, who had been born in the meantime. Starting pregnancies was not difficult for Gabi and so Philipp was soon on his way. Not that I’m forgetting, Gabi had two very early miscarriages while she was still working as a pediatric nurse at the Marburg Children’s Hospital.
So now the third pregnancy. Everything remained calm until around 28 weeks. Then the contractions started again. Still thinking about the side effects of Partusisten, I looked for ways to reduce the dose. I had observed that the frequency of contractions in pregnant women with premature labor was not evenly distributed throughout the day. As palpitations as an indicator of the effect occurred quickly after taking a Partusisten tablet, including the effect on the uterus, I only wanted to give the tablets at the times with the highest frequency of contractions. I therefore asked all patients to fill in a sheet of paper, which we called the „daily labor plan“. A line was drawn in a time box for each contraction they felt. Almost all patients showed a kind of circadian pattern. I then determined the dosage according to the frequency. Gabi also filled out this „daily labor plan“.
As if the premature contractions weren’t enough, Gabi suddenly developed calf cramps. Which substance was safe for pregnant women and fetuses to treat calf cramps? I didn’t need to do a long literature search. I immediately came across magnesium. Overdoses were hardly possible when taken orally. A soft stool was sometimes desired by the patients. The pharmacist at the Pilgrimstein pharmacy opposite the women’s clinic gave me a magnesium preparation that he usually sold for calf cramps. Just a few hours after taking it, the calf cramps disappeared. But also
the contractions were as good as gone. This was also impressively reflected in the „daily labor plan“. As we had not expected the reduction in the frequency of contractions, the disappearance of premature contractions must have been due to the intake of magnesium. More than a real eureka effect.
On the way to Zurich
How should we deal with this observation? Virtually nothing was known about magnesium in medicine. In obstetrics, eclampsia was treated with very high doses of magnesium intravenously. No connection had previously been published between premature labor and magnesium. In cows, pasture tetany was described when the grass had too little magnesium in spring. It was also not possible to determine magnesium precisely in serum. In the medical clinic in Marburg there was a senior physician who had been provided with an atomic absorption photospectometer by the German Research Foundation. He was able to use it to analyze magnesium in serum. However, it was hardly possible to include this determination in our routine blood tests. The colleague also had a barely perceptible willingness to carry out the tests for us.
Did this also work for other patients with premature labor? We therefore gave magnesium in addition to the usual tocolysis with Partusisten. It was impressive to see that almost all patients could be switched from intravenous Partusisten therapy to oral therapy.
I had gained these results at the Women’s Clinic in Marburg. In 1980 we moved to Zurich. Albert Huch and his wife Renate had already done a lot of research in the newly developing field of perinatology. They had made a name for themselves with their transcutaneous measurement of oxygen in newborns. Gabriel Duc was head of the pediatric clinic in Zurich and wanted to develop the field of perinatology at the university hospital. He therefore campaigned for the Chair of the Women’s Clinic to be split into one for gynecology and one for obstetrics. The previous head of the Women’s Clinic, Werner Schreiner, was very angry about this, which I later realized .[2] The chair was now shared and Albert Huch was able to move to Zurich to set up the obstetrics clinic there. He was given a generous amount of space to set up a „perinatal physiology laboratory“. It had to be filled. Naturally, his wife Renate, who was to manage the laboratory as a physiologist, went with him. Henning Schneider, who had previously come to Marburg from New York with his placenta perfusion in my ovarian perfusion laboratory, was also to become a senior physician and conduct research there. We had already been in Marburg long enough by then, our three children had been born and so my Gabi was very supportive of the offer to come to Zurich as a postdoctoral fellow. I completed my surgical training as a gynecologist in Marburg and we followed the Huchs to Zurich.
There I helped Henning Schneider with placenta perfusion and also devoted myself to evaluating the results of my magnesium supplement therapy. The results were published in 1981. Now this story took off. Many studies were started, not only in my own clinic. Many also began to gain experience with magnesium and premature labor.
I had done some research: Magnesium aspartate hydrochloride from Verla Pharm was the best-studied magnesium salt and so I used this salt for my research. Joachim Helbig was the head of the scientific department of this company. He showed me the graph of the sales figures that he had painted on the wall in his office. He had to adjust the scale several times in the first year. Turnover went through the roof in the truest sense of the word. The success was not the worst thing for my work. Huchs negotiated with the company and I got a computer. So I had a great PC for my evaluations very early on. PCs were really expensive back then. And the collaboration with Verla Pharm was also of mutual benefit in later studies. But more on that later.
Foundations for our observation
Considering that magnesium was necessary for many metabolic steps, but little was known about magnesium in clinical medicine, it was necessary to learn as much as possible about the causes of our observation. So we began by examining the electrolytes in the serum during our therapy. It was also necessary to show that the administration of magnesium was safe. After all, we were treating expectant mothers with their unborn children. In addition, we wanted to avoid a flash in the pan of our observation in obstetric therapy at all costs. This threatened to happen, as magnesium was suddenly supposed to be good for and against everything.
The following questions arose: What are the normal values during pregnancy? Is it possible to draw conclusions about the occurrence of premature labor from a determination of magnesium in the blood? How does the magnesium serum level behave during the course of pregnancy? Does magnesium remain constant as an intracellular ion in the uterine musculature during the course of pregnancy? And if there is a reduction in the magnesium level in the myometrium and in the serum, what is the reason for this? What could be the cause of the magnesium deficiency and why do not all pregnant women suffer from a deficiency?
Magnesium in the myometrium
It was a good thing I was in Zurich. There were institutes here that could carry out the necessary analyses. So I found the biochemist Peter Kunz at the Institute of Biochemistry at the ETH, the Swiss Federal Institute of Technology, in Zurich, who agreed to carry out the tissue tests. We found scientists who could advise us on this at the „Society for Magnesium Research“, which had been founded a few years earlier by Hans-Georg Classen in Hohenheim. There, Theo Günther, head of the Institute of Molecular Biology and Biochemistry at the Free University of Berlin, explained to us how difficult it is to determine intracellular magnesium. But we managed it. We took a cubic centimeter piece of tissue from the uterotomy and the corresponding blood samples from around 100 caesarean sections. Both for women with premature caesarean sections and around the due date. A little experience showed me that the logistics of taking the samples worked well. I had finished the series of examinations, but not everyone had realized that yet. During a caesarean section, a young midwife whistled at me to take a tissue sample. So I could assume that the samples were taken during all caesarean sections. So what did we find? The magnesium level in the tissue actually falls in parallel with the serum. Anyone interested in the more detailed data, but also in the other studies mentioned, can find the relevant publications on my website spaetling.net.
The rare coincidence of premature labor and caesarean section made it impossible to prove that the magnesium content in the uterine tissue was also reduced in premature births.
Why is magnesium low during pregnancy?
My habilitation thesis dealt with the question of how lung and heart function changed during pregnancy at rest and at work[3] . Well-motivated pregnant women came to the lung function laboratory, which we had set up in the „Perinatal Physiology Laboratory“, at fortnightly intervals. I asked my test subjects if they could donate some blood and urine each time. And so we were able to establish that magnesium excretion does indeed increase during pregnancy. It drops again immediately after delivery. How could we explain this? We know that the cardiac output increases in parallel with the heart rate. And parallel to cardiac output, primary urine is formed, with a quantity of electrolytes. To prevent damage, a large proportion of the electrolytes must be reabsorbed. Now the site where the large quantities of sodium are reabsorbed is exactly the same as the reabsorption site for magnesium. However, sodium is more important for survival than magnesium. The reabsorption of magnesium is therefore hindered and magnesium appears more frequently in the urine. Magnesium is therefore increasingly excreted during pregnancy, although the expectant mother needs more magnesium for her child and for herself. Women whose magnesium intake or reabsorption is only just sufficient are therefore suffering from a magnesium deficiency. –This is probably a small negligence on the part of evolution. It can’t think of everything.
The double-blind thriller
The whole time I had to think about it: no matter how much research we do on the effects of magnesium in pregnancy, if we don’t succeed in conducting a proper clinical study, many women will be deprived of the beneficial effects of magnesium on pregnancy.
So we planned a prospective randomized double-blind study. At the beginning of the 1980s, the clinical science world had not yet committed itself to the (GCP) Good Clinical Practice guidelines and so I was looking for someone in Zurich who could advise me on planning the study. There was a small statistics institute for this purpose. The question of the placebo content was quickly clarified. If we wanted to use magnesium aspartate hydrochloride as the active substance, aspartic acid was a good placebo. If we wanted to include as many patients as possible, several hundred, in the study, our polyclinic was the obvious choice. But how should we logistically organize the distribution of the enormous quantity of tablets? The suggestion was made to produce a batch of 85, for example, for all women with odd birthdays and a batch of 84 for those with even birthdays. Only the manufacturing company, i.e. Verla Pharm, should know which of the two batches contains magnesium. That’s how we did it, a bad decision in retrospect.
It took some time before we were able to include a sufficient number of women in the study. It was also not always easy to motivate doctors in the outpatient clinic to accept the patients. You mustn’t forget that I was German and had been appointed senior physician, a position that one or two Swiss doctors would have liked to have. But constant research was not possible with the Swiss at that time. Shortly after gaining their clinical qualification, they settled down as attending physicians with lucrative surgical jobs, for example at the Hirslanden, a well-known private clinic in Zurich.
Evaluation of the study
Of course, it also took longer because all the participants still had to give birth to their children. Only then were the medical histories evaluated. This was done by my Gabi, who was very motivated by her experiences. She had experienced the effects of magnesium first hand. The completed data sheets were typed into an input mask and the data was then evaluated by Falk Fallenstein, the physicist in the perinatal physiology laboratory. He later joined me in my research department in Herne.
The results were impressive. What we had not expected at all: in addition to the figures for pregnancy prolongation, there was significantly less bleeding in early pregnancy and cervical insufficiency. We were not aware of any published studies on this. In our study, we started giving magnesium as early as possible and no later than 16 weeks. In this way, early pregnancy, in which these disorders are seen more frequently, was also recorded. This observation did not lead to an official recommendation. In any case, my advice is to always prescribe magnesium in sufficient quantities from the positive pregnancy test onwards.
The number of births under 37 weeks was probably not significantly lower, but a third more women had to be hospitalized in the placebo group. The diagnoses of bleeding, cervical insufficiency and premature labor were significantly more frequent. The number of small premature babies who had to be treated in the neonatology department was significantly lower after magnesium. They were fitter than those without a magnesium pregnancy.
Reactions to the double-blind study
The reactions to this publication worldwide were not as positive as we had hoped. Along the lines of: that’s too simple, it can’t be. Of course there are other causes of premature labor and premature birth, e.g. vaginal infections. But this complex is (probably) completely separate from the contractions caused by too little magnesium. Premature labor is a symptom. And in medicine, one symptom can indicate several disorders.
I received many invitations. The most impressive for me was the invitation from the National Institute of Health (NIH) to Cape Cod, not far from Boston. I had to really struggle there, not only because my English was suboptimal, to put it mildly. The latent accusation against my results was that the study was not conducted according to GCP guidelines, which did not even exist at the time the study was planned. The study was probably double-blind, but they found fault with the randomization.
I would like to explain it like this: Since one of the two batches contained magnesium, we could have analyzed the contents. With this knowledge, we could then have allocated the placebo batch to the women with an unfavorable pregnancy history, which might have led to poorer results in the group without magnesium. My Gabi could also have used this knowledge to influence the evaluation. Our study is described as controversial in the literature and the specialist societies for obstetrics and gynecology have not issued an official recommendation for the general administration of magnesium during pregnancy based on our results. Not every pregnant woman is given magnesium, but I believe that the administration of magnesium is part of the repertoire of all gynecologists worldwide and that many women take magnesium even without a prescription. Incidentally, this is a phenomenon that makes subsequent double-blind studies impossible[4]
I was so annoyed by the comments of a certain Mr. Sibai from America. He had also carried out a double-blind study and saw no differences between his groups and therefore claimed that magnesium had no influence on the course of pregnancy. If Sibai had read our work in full before making his comments, he would have noticed that even if our study could not be conducted according to GCP rules, our randomization was correct. There was no difference in the anamnestic data between the groups . In his study, Sibai wanted to investigate the influence of magnesium on pre-eclampsia, a condition in pregnancy that is associated with very high blood pressure. This condition is common among young black women giving birth to their first child. He therefore chose this group and only gave them magnesium or placebo after 20 weeks of pregnancy. In addition, all subjects, including those in the placebo group, received a multivitamin-electrolyte supplement with one third of the amount that our magnesium group received. Our test subjects also represented a completely normal group, which included women who had given birth more than once. At the time Sibai started supplementation, most of them had already been taking magnesium for over 10 weeks. As he had included far fewer women in his study than we did, he also claimed that if he had increased the number of cases tenfold, he would not have seen any differences in his study. However, as he had not made this calculation in his publication, we did it for him. And lo and behold, there were large differences in birth weight, in placental weight as an indicator of infant malnutrition. And this also occurred more frequently in his magnesium-free group. In addition, the children had a poorer Apgar score. So we assume that with earlier supplementation and a truly magnesium-free placebo group, he would have seen at least the same differences as we did.
No matter how annoyed I was, there was nothing I could do apart from writing a letter to the editors of the journal. At this point I have to criticize many of the scientists and clinicians involved. How many women and their children around the world could be better off if they had read our study better and written guidelines that were more nuanced about magnesium administration during pregnancy. As if there had been no good science before the GCP rules.
University Women’s Hospital Bochum/Herne
I had not yet reported on how I came to the Marienhospital in Herne, as our research into magnesium continued there. The Ruhr University initially planned to build a university hospital on the campus in Bochum. However, as there is a hospital on every corner in the Ruhr region, there were fears that the mountain of beds would increase. Suitable clinics were found in the largest hospitals in and around Bochum and habilitated heads were appointed to manage them in order to be able to practice university medicine. As a result, some clinics around the campus became university hospitals and the „Bochum model“ was established. There was a university women’s clinic at the Marienhospital, but no research was carried out there.
In Zurich, as a „Usländer“, I initially only had a work permit for two years. However, as I was needed in the clinic and in the perinatal physiology laboratory in Zurich, this was extended from year to year.
I can’t say that my relationship with my boss Albert Huch was unclouded, especially in the last few years. And so I received a letter through him from the Zurich cantonal administration telling me that I had to prepare my departure in the following months. My boss did not object to this letter. I was gripped by a certain panic, as I was in the middle of working on my habilitation. It was clear to me that I would not be able to follow the „official channels“. So I took heart, went straight to the person in charge at the Health Directorate and presented my problem. „How much longer do you need?“ I was asked. The year I suggested was approved immediately and without any problems.
This also gave me some time to look for a follow-up position. So I looked at the women’s clinic at the Marienhospital in Herne, not least because my Gabi and I had grown up in Duisburg and Herne was somehow part of the Ruhr region, but more of the Westphalian part, whereas Duisburg is part of the Rhineland. The boss there, Quakernack, wanted to take me on, but he couldn’t offer me a laboratory. So how could I get a lab?
Establishment of a research department
I asked the hospital administration for suitable rooms. They found rooms in the basement of the staff building where junk was stored. But just because I wanted to continue my research, these rooms would not be renovated for research purposes. I asked the German Research Foundation (DFG) and sent an application about the possibilities for feedback control of pulsatile bolus tocolysis. Falk Fallenstein and I had developed bolus tocolysis, an intermittent delivery of the labor-inhibiting agent fenoterol (see above) in the Zurich laboratory and had also carried out the first positive studies with pregnant women. Because our research had already been funded by the DFG since ovarian perfusion with Ekkehard Stähler and the then Director of the Women’s Clinic Rudolf Buchholz in Marburg, it was possible to imagine funding there. But I was told that only positions and equipment directly related to the research question of the project could be funded. So no furniture, no computers, no printers, etc. With this information, I went back to the hospital administration. They would be happy to prepare the rooms for me, but they wouldn’t pay for the furniture etc.. Nor would they pay for the other basic equipment.
What to do?
Now, research and teaching are essentially a matter for the federal states, so I contacted the Ministry of Science in Düsseldorf, which initially wanted a precise application. I was able to formulate this well for our project. I outlined the willingness of the DFG and hospital administration and attached a list of the necessary basic equipment to the proposal. A short time later, I was invited to Düsseldorf, where I was greeted with the sentence: „Dear Mr. Spätling, there are benches in the annex.“ – funny – just Rhineland. Since then, I have only included everything „as“ an attachment.
The main news, however, was that they were willing to provide me with the necessary money if the hospital operator would also convert the rooms into a laboratory. With this information, I approached the hospital administrator again. „What furniture do you want to furnish the laboratory with once it has been converted?
Verla Pharm had benefited „a little bit“ from our research, an extension for drug production had been started in Tutzing and so I asked them for support in procuring furniture. The necessary amount was gladly made available and the furniture was purchased. Incidentally, the furniture was of such good quality that many of them are still in use today, over 40 years later, in our foundation and in the family school.
With the three commitments, the Marienhospital was then ready to convert the rooms. And they did a really nice job.
Now the DFG also approved our application. We now had the equipment and personnel to not only carry out the studies on uterine motility and feedback control, but also to continue our studies on magnesium.
Studies on magnesium absorption and interaction
From my very first steps in the world of magnesium, Hans-Georg Classen was a great supporter of our research. He was the head of the Institute of Pharmacology and Toxicology in Stuttgart-Hohenheim, had founded the Society for Magnesium Research and also had a few hard-working female students. One of them was Gaby Disch with laboratory experience. We were able to motivate her to work alternately in our laboratory and in the laboratory in Hohenheim as part of her doctoral thesis, as a rat house was also available there. We have her work to thank for the fact that pregnant women can take magnesium and iron at the same time. We also experimented with methods for measuring ionized magnesium, as this proportion in the blood was the main factor responsible for the effect. However, the results were so scattered that they could not be used for clinical purposes and our results were only sufficient for presentations at specialist societies.
As a link between the clinic and the research department, we applied to the DFG for an assistant position, which was filled every six months from the group who had qualified as gynecologists. Quite soon after the opening of the research department, we had a medical-technical assistant, Christine Lehmann, who was fresh out of school. She worked so quickly that we, Falk Fallenstein and I, could hardly keep up with the work. She studied our business with the rotation assistants[5] and assistants for a good year. After this year, Ms. Lehmann dared to study medicine as well. After the Physikum, her doctoral thesis was due, which she naturally did with us. There was always the question of whether the daily dose of magnesium could perhaps only be taken once a day. So we investigated and answered this question in her thesis. Of course, much more magnesium is absorbed if the daily dose is taken in three divided doses. Now we had it in black and white. Thomas Cunze, another doctoral student, completed the determination of magnesium in the uterine muscle that he had started in Zurich with Peter Kunz.
Chvostek and magnesium
I also got to know Jean Durlach from Paris through our Society for Magnesium Research, which I will discuss later. He was president of the „International Society for the Development of Research on Magnesium“ (what a great name) and editor-in-chief of the journal „Magnesium Research“. I was able to visit him on the occasion of a lecture in Paris. Magnesium deficiency is easy to determine, he said more than once. You only have to look for the Chvostek sign. If you were to tap the facial nerve near the temporomandibular joint with a reflex hammer and the upper lip would twitch, you would have a magnesium deficiency. In the literature, Chvostek is described as a sign of calcium deficiency. That would be nice if it were so easy to detect a magnesium deficiency. Low magnesium in the blood is a poor description of a deficiency, as magnesium is an ion that is more likely to be in the cell than in the serum.
So I looked for someone at the Ruhr University with whom I could carry out appropriate experiments. We were then able to set up a great experimental setup with electromyography and measurement of lip twitching with the help of video recording in the neurological clinic at the Knappschaftskrankenhaus in Bochum-Langendreer. The results were as expected. It would have been too good to find a magnesium deficiency with the Chvostek sign. We only found a slight correlation with calcium levels. But that’s what Chvostek had in mind. Unfortunately, our colleague at the Neurology Clinic had no impetus to publish the results and so there was only one lecture.
Invitations and publications
Now, the size of the women’s clinic was not comparable to the women’s clinics in Marburg, Zurich or later Fulda. But if you wanted to provide obstetrics at a high level, you had to stay in the clinic during on-call duty so that you could intervene as quickly as possible. That was good for the clinic, usually good for science, but not always good for the family. You can work out how much time I spent in hospital with four senior physicians, especially during vacation periods. For example, I said goodbye to the family on a weekend shift on Thursday evening and came back on Monday evening. Then there were the many invitations. I already mentioned the invitation to an NIH conference above. I was also in Blacksburg/Virginia, Cape Town/South Africa, Kyoto/Japan, Bones-Aires/Argentina, Stockholm/Sweden, Rome/Italy, Paris/France, Tenerife/Spain, Lisbon/Portugal, Bangkok/Thailand and various places in Germany, Austria and Switzerland. Only rarely was I able to take Gabi and the children with me. Sometimes there was „joy“. However, I was so convinced of the importance of the lectures for my scientific career that I only turned down invitations to India and Australia. And there was also something missionary about it. I just wanted as many women as possible to benefit from our knowledge of magnesium. I still want that today. Perhaps that is also a motivator for this report and my homepage.
I now had time for evaluations, doctoral theses and writing publications while I was on call and working nights. Karl-Heinrich Wulf, the professor at the Würzburg Women’s Clinic, once said after my presentation on the double-blind study: „I don’t believe it.“ But he soon asked me to write an article on early preterm birth for the journal „Der Gynäkologe“. This and other handbook articles, in which magnesium, but also the findings on labor inhibition with fenoterol, bolus tocolysis and four-channel tocography played an important role, consolidated our position in the field of diagnosis and treatment of premature birth. And all this contributed to the fact that I was later entrusted with the management of the Fulda Women’s Clinic. I am grateful for that.
Women’s Clinic at Fulda Hospital
Of course, all pregnant women in my clinic received magnesium, and I hope that this is still the case today. But I was no longer able to do systematic research with magnesium there. Even though Falk Fallenstein came from Herne to Fulda and we also set up a small research department here with the help of the German Research Foundation. We mainly worked on bolus tocolysis, four-channel tocography and later on cerclage and total cervical occlusion. We also developed procedures for severe bleeding after birth, such as the stitching technique and sumo compression. And then there was the foundation with its family school. And of course I was usually in the clinic from morning to night, and often at night too, because obstetrics is a „hot“ subject. Emergencies arise damn suddenly and it’s often too demanding for a young senior doctor alone.
Society for Magnesium Research
But I couldn’t let go of magnesium. So I took over the presidency of the Society for Magnesium Research, the society that brought together those who dealt with magnesium, whose members I could always ask for advice. Here in Fulda, we then held board meetings and the annual symposia. Fulda is particularly suitable for this because of its central location in Germany. The venues for the essential accompanying program also delighted all those who came here year after year. The clinic’s auditorium and the associated rooms were so easy to use that I was still organizing the symposium years after my retirement as head of the clinic in 2014 and handing over the presidency. We were now working on the hope that magnesium deficiency would be considered more frequently in clinical medicine as the cause of some diseases or disorders. First of all, it should simply be determined more frequently in routine clinical practice. It remains difficult to get doctors to think about magnesium for an ion that plays a role in over 300 enzymatic reactions in the body.
Concluding remarks
It was a happy coincidence that my Gabi, of all people, had these unfortunate premature contractions, that she noticed that the magnesium not only reduced the calf cramps but also the premature contractions. It was also a coincidence that I had some experience with ovarian perfusion and therefore had the courage to work on clinical issues. This observation motivated us both to investigate the connections further. Even if „it was not meant to be“ that our double image study complied with the GCP rules that were only developed later and therefore did not achieve the „breakthrough“ that we had hoped for. Nevertheless, we were able to ensure that most gynecologists think of magnesium in the event of premature labor, thus sparing many women a therapy that is often full of side effects and often unnecessary.
It was worth it.
Ludwig Spätling, April 2025
[1] We carried out investigations into this. As testosterone and other hormones that could have stimulated hair growth were not elevated, we came to the following interpretation: the labor-inhibiting betamimetics widened the skin vessels so that more blood flowed through them. The skin was thus compared to a well-watered meadow, where the grass thrives better. Incidentally, the hair growth receded completely after the end of treatment.
[2] I was not allowed to work in gynecological surgery. But to work in a managerial position at a women’s clinic, you need to be qualified in the entire field.
[3] Mario (KTM) Schneider and I examined the functions of standing and sitting in parallel. Here we found what we called the „standing phenomenon“: When standing, the heart rate increased up to a certain point at which the uterus contracted. Then it dropped again. We interpreted this as follows: The soft uterus obstructs the venous return of blood to the heart when standing. When the uterus contracts, it rests on the spine and releases the vena cava so that the blood can flow back to the heart and the heart does not have to compensate for the low blood return flow with an increased heart rate. Mario was able to habilitate with his research into this phenomenon.
[4] Verla Pharm had now tried to obtain an indication for pregnancy. This was rejected by the BfArM (Federal Institute for Drugs and Medical Devices) with the arguments described above. So I went to Berlin and once again explained the successful randomization in our study. „Then why don’t you do a new study?“ they said. When I pointed out that it would not be possible to form a group that would not take magnesium because the positive effect was already known at least throughout Europe and everyone could obtain magnesium, the answer was: „Then go to Russia or at least to the Eastern Bloc“. I was at a loss for words.
[5] At this point, I would like to add that obstetrics and gynecology were also becoming increasingly female in our women’s clinic in Herne. As female doctors are not allowed to work clinically during pregnancy, the rotation position in our research department during pregnancies was ideal.