pre-eclampsia

Notes on Thiamine and Pre-Eclampsia: The Sugar Connection

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If you have read any of the articles on this website or anything relative to modern thiamine deficiency, you are aware of the connection between sugar consumption and thiamine deficiency. The more sugar, in any form, that one consumes, the more thiamine one needs to process it. This is because thiamine is the rate-limiting step in the metabolism of glucose into ATP. This pathway can be overwhelmed easily by the high sugar and low nutrient content of modern foods. The mismatch becomes particularly evident during pregnancy, where increased energetic demands may lead to insufficient thiamine independently of sugar intake if one is not careful, but also may be compounded by sugar intake. A study published in 1969 looking at thiamine and pre-eclampsia elegantly illustrates this point. Pre-eclamptic women, it appears, have a problem with sugar metabolism and the logjam is insufficient thiamine.

Pre-eclampsia

Pre-eclampsia, which affects up to 6% of all pregnancies, is marked by dangerously high blood pressure, edema, proteinuria with kidney damage and potentially damage to other organs. There is a high risk of stroke and other serious, even fatal complications, for the mom. For the fetus, because of the impaired functioning of the placenta, placental abruption is possible along with growth restriction and pre-term birth. There are few useful treatments, beyond bedrest and early delivery, but even then mom’s health may continue to be at risk. Postpartum spikes in blood pressure, called postpartum pre-eclampsia, affect up to 27% of women. As bad as these numbers are, they are likely even worse, given that most women are seen in the emergency rooms where the association with pregnancy is not regularly tabulated.

Metabolic Disturbances, Thiamine, and Pre-eclampsia

Pre-eclampsia has long been associated with metabolic derangements leading to poor energy metabolism of the placenta and mom alike. Although some have considered the role of thiamine in pre-eclampsia, the research has been mixed, generally decades old involving non-Western populations where food insecurity and not excess drives deficiency. In all, the research is sparse at best.

Although this particular study is older, its unique design merits discussion. Specifically, it shows that the activity of a thiamine-dependent enzyme that is responsible for a key aspect of the metabolism of glucose into ATP is impaired or overwhelmed in women with pre-eclampsia. This impairment then, leads to both maternal and placental energy deficits, which in turn, result in poor maternal kidney and cardio-metabolic function and all of the negative sequelae associated with pre-eclampsia.

Depending upon the severity of the impairment though, the problems with thiamine and subsequently glucose metabolism may not be noticeable unless challenged. That is, early on in the disease process, despite symptoms of pre-eclampsia, the metabolic dysfunction associated with insufficient thiamine are hidden with typical testing. It is not until the patient either faces a metabolic challenge, such as the one devised by the study below, and/or the disease has progressed sufficiently in severity that the thiamine issues may be detected.

Study Details

Backing up just a bit, let us look at this study more closely. Here, three groups of pregnant women were recruited: a healthy control group, a mild pre-eclampsia group (BP >160/100, plus edema and albuminuria) and a hospitalized eclampsia group. Instead of measuring thiamine directly, which has a high rate of false negatives, the researchers devised a challenge test wherein blood pyruvic acid concentrations were measured fasted and then 30 minutes following the administrations of dextrose.

Recall, thiamine is required for pyruvate dehydrogenase (PDH), the gatekeeper enzyme within the mitochondria, responsible for taking pyruvate (derived from glucose) and converting it into acetyl CoA, so that after a series of reactions, ATP can be produced. This pathway is called oxidative phosphorylation or OXPHOS, because the reactions require oxygen. With OXPHOS and sufficient thiamine, for every molecule of glucose, the mitochondria synthesize 30-38 units of ATP. This is compared to only 2 units of ATP produced via glycolysis, the intracellular pathway that converts glucose into pyruvate.

Pyruvate or in this case, pyruvic acid, is inversely associated with thiamine concentrations such that when thiamine is sufficient, pyruvic acid concentrations are low, even in response to the ingestion of sugars. When thiamine is low, however, pyruvic acid skyrockets. This means that a higher than expected pyruvic acid in response to the ingestion of dietary carbs or in this case dextrose, would indicate a logjam at the PDH, likely associated with low thiamine. Since the PDH enzyme also utilizes riboflavin and lipoic acid, it is possible that these nutrients may also be involved. Similarly, if any of these nutrients are severely low or this enzyme is more completely overwhelmed, we would expect to see elevated pyruvic acid even when fasted and even higher concentrations after the dextrose challenge. And that is exactly what these researchers found.

Compared to the healthy group, fasting pyruvic was similar but increased significantly after the dextrose challenge in the less severe pre-eclampsia group. For the hospitalized eclampsia group, however, both fasting and challenge pyruvic concentrations were elevated significantly. The healthy range for pyruvic acid is .5mg-1mg. Pyruvic concentrations in pre-eclampsia fell within the range while fasted but their numbers shot up, in some cases over 2mg. The average was 1.62 (SD .4). For the hospitalized group, pyruvic was elevated both when fasted (r=1.05mg) but especially with the dextrose challenge (r=1.93mg, SD .26).

Whoa.

Let’s put this in context. We use sugars (and fats, but that is another story) to make ATP. ATP is the energy currency produced by the mitochondria and used by all of the cells to do the things they need to do. Not enough ATP means not enough energy. Imagine trying to grow a new organ like the placenta and a new human without sufficient ATP. It just will not work out very well. Something will have to give. In this case, maternal kidney and heart function suffer. Both require huge amounts of ATP.

Getting pyruvate though PDH is the rate-limiting step. If the PDH does not have its cofactor nutrients, it will not work well and if it is not working, not much else will either. I should note that there are several other thiamine dependent enzymes in this and other pathways that control the metabolism of fats and proteins as well.

So, if pyruvate cannot get into the mitochondria and be worked on by the PDH, not only will ATP production decline and pyruvic build up at the gates of the mitochondria, but in an effort to rid the body of the excess pyruvate, some of it will be transported to another enzyme called lactate dehydrogenase or LDH. LDH and PDH work together to generate back up energy by converting pyruvate to lactate and back again. If one is healthy, lactate can be used as a fuel source and fed back into the mitochondria but only if one has sufficient thiamine to run the PDH. If thiamine is lacking, all of that pyruvate and lactate build up and that is what we see here. The PDH is not working well and so concentrations of pyruvic acid and likely lactic acid, though not measured, increased especially in the presence of a dextrose challenge and as the disease processes progresses in severity.

Final Thoughts

What this study tells us is that there is problem in this pathway that may not be readily apparent biochemically unless stressed appropriately, in this case, with dextrose but I imagine any high carbohydrate diet might produce the same reaction. And since, thiamine is involved in other metabolic pathways, I suspect had the researchers devised challenges to test them as well, we would likely have seen a similar pattern. While this study looked at pregnant women specifically, this pattern holds across all populations. The body adapts for as long as it can, but the chinks in the system are there. We simply do measure them appropriately in the early stages of disease – with challenge tests.

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Pregnancy Toes – What Sugar Does to Feet

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Pregnancy toes are really swollen feet and swollen toes. The name stuck in my mind because one of my daughter-in-laws is pregnant and I was sent a photo from her winter vacation in her flip flops in the snow and winter coat—she was not able to put her boots on because of her swollen feet (swollen even in the cold!).

I did not think much about it until she came to visit me yesterday and I noticed the flip flops and her chubby toes. She had “pregnancy toes” again she said. It then suddenly all became clear. I asked her: did you by any chance have any sugar today? And she said “as a matter of fact, yes!”

I reached for my salt pills that I use for my migraines as do all members in my migraine group on Facebook and handed her one. I really should have photographed what happened but I did not think the effect was going to be so fast and so big. Less than 15 minutes after she took the salt pill and a glass of water, her toes went back to normal. We ended up laughing it away. Had she known this, she could have worn her boots in the snow after all!

So what did her pregnancy toes have to do with sugar and salt you may ask? Previously, I quoted from the Harrison’s Manual of Medicine an important paragraph that I repeat here:

…serum Na+ falls by 1.4 mM for every 100-mg/dL increase in glucose, due to glucose-induced H2O efflux from cells. (page 4)

The above means glucose (part of sugar) and sodium (part of salt) are in inverse relationship. As you increase sugar, salt drops and water is sucked out of your cells by sugar like a giant Slurpee machine. The water then collects on the outside of your cells rather than the inside, thereby dehydrating your cells and at the same time make your body swell. Edema is often associated with too much salt, but in fact, it is too much sugar. Being always thirsty is associated with Type 2 Diabetes but it is also associated with not having enough salt in the body since without salt the cells cannot get hydrated.

In light of this fragile balance between sodium and glucose in the blood, are we treating pregnancy edema, gestational diabetes, and other maternity complications, the way we should? Consider that with pre-eclampsia (gestational hypertension), women are told not to eat salt. You can see what happens when we reduce sodium: glucose increases and we also induce an ionic imbalance. This ionic level imbalance is visible (like the swollen toes) and may lead to further complications. There are two problems that we are facing here: first if she does not eat salt, her sodium-potassium pumps cannot work–this may cause migraines and headaches as I often see in my migraine group. Secondly, as you saw the fragile balance between the see-saw action of glucose and sodium, if she stops eating sodium her glucose may increase, causing swelling. This is an interesting theory to ponder – one that merits research.

Sodium and Glucose Work Together

Salt breaks up in the body into sodium and chloride. Sodium attracts water and holds onto it inside the cells. It keeps chloride outside of the cells to ensure proper voltage and electrolyte balance with the aid of potassium. When you eat sugar, the glucose part of it removes the water from the cells via osmotic channels that are too narrow for the sodium ions to exit. Thus, one ends up with a ton of water outside the cells with sodium inside hugging a tiny amount of water. Swelling occurs as the water leaves the cells but remains between cells.

Given the inverse nature of glucose and sodium in the blood, if one is swollen as a result of too much sugar, eating salt will take the water back from sugar and move it back into the cells–as it did for my daughter-in-law’s pregnancy toes. What is important in this information is this:

  1. If you feel swollen after eating sweets, you need to eat salt and drink a bit of water to reduce your swelling.
  2. If you have Type 2 Diabetes or are hypoglycemic, eating a salty meal can give you a major sugar crash and land you in the hospital!
  3. Eating sugar of any quantity will dehydrate your cells and you and make you run to the toilet every 30 minutes.

Because glucose takes water out of the cells, the edema that follows increases extra-cellular water and causes swelling in the body. This extra-cellular water needs to be reabsorbed into the circulation for the kidneys to be eliminated. To be reabsorbed, sodium is necessary since without sodium, the cells cannot operate their voltage gated sodium pumps and so the gates cannot open to grab glucose to take it into the cells and to get the water back into the cells. I think you can already see the contradictions in the logic of reduced salt: the mom-to-be is told to not eat salt, this causes extra-cellular water and swelling, which needs salt to be reabsorbed into her cells for clearance by the kidneys but which she is not allowed to eat. This way ionic level balance is not possible and chain reactions may occur with negative consequences. She may have protein leaching into her urine, extra hard kidney work, and a whole other long chain of complex events may kick in to make pregnancy a rather unpleasant experience risking the health of the fetus.

The amount of extra-cellular water is very hard for the body to get back into circulation without salt and may take days, taxing the kidneys with the volume of water leaving and increasing pressure on the blood vessels from the outside, causing high BP. However, as the volume of water is leaving the body finally, this reduces blood pressure. When a pregnant woman’s blood pressure drops as a result of all that water leaving, the dehydrated blood cells carry less oxygen. This indicates reduced oxygen for both her and the baby.

By telling mothers to reduce salt intake, glucose increases, which increases blood pressure (BP) rather than reduces it. The similar phenomenon happens in gestational diabetes. In gestational diabetes (and gestational hypoglycemia as well) the sugar level is unstable and is either too high or too low, respectively. Should the mother-to-be eat a salty pickle (as cravings always dictate pickles), she may end up in a major sugar crash and in the hospital for immediate treatment.

The balance between sodium and glucose is very fragile and extremely quick changing as you could see on my daughter-in-law’s foot. Interestingly we now also know that salt does not increase blood pressure but sugar does and so a reduced salt diet automatically increases blood pressure because of the glucose and sodium inverse connection and sugar’s dehydrating properties. Reduced salt also increases triglycerides (Graudal, 2011), causing a lot of problems for people with preexisting heart conditions. So by reducing the salt intake of the mothers to be, are we creating diabetic mothers and/or babies? Babies have been born with diabetes 2!

Is it possible that we are giving the wrong advise to pregnant women about salt and sugar? It’s an interesting question to pose and further research is badly needed. Knowing that salt and sugar are in inverse proportion in the blood, one may suggest eating them together. In fact, eating them together is a much better idea than eating sugar alone. It is best to not eat sugar at all but if you must eat sugar, consider eating salt too.

Sources:

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Graudal et al., Cochrane Database Syst Rev. 2011 Nov 9; (11).

This article was published originally on Hormones Matter on February 15, 2015. 

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

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How to Have a Healthy Pregnancy: Avoiding Preeclampsia and Toxemia

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A few months ago, I received a book from a doctor who had retired from his specialty in obstetrics and gynecology. It was accompanied by a letter that began as follows, “I am writing to you, because I have found another mortal being who is particularly interested in the biological activities of thiamine. I had previously thought that I was nearly the lone believer in the benevolent effects of thiamine, particularly for the treatment and prophylaxis of the toxemias of pregnancy and its many associated problems”. In this letter, he went on to tell me that he had hired himself out, in his retirement, to the government of the Commonwealth of the Northern Mariana Islands “to improve upon their system of obstetrical care”.

Severe Preeclampsia

On his first day he attended an introductory meeting with a group of island doctors who were all American Board Certified in their specialties. Their purpose was to introduce him to a patient who was 36 weeks pregnant. He described her as “essentially moribund” with severe preeclampsia, gestational cardiomyopathy, and some separation of the placenta (preeclampsia is the term used for severe pregnancy toxemia and cardiomyopathy is the term used for a sick heart. Separation of the placenta would mean that there would be bleeding into the uterus). She  was so sick that she had orthopnea (breathlessness while lying flat on her back. She could only breathe when sitting up in bed, a characteristic of heart failure). Spontaneous labor and delivery, he said, most likely would cause maternal and fetal death and that she would fail to come through a cesarean section. All in all, this was considered by all of the island doctors concerned to be a hopeless case. He suggested that she had beriberi, the vitamin B1 deficiency disease. The letter went on to say “in a private huddle the doctors decided that if the patient died while they were holding me up, they would be found solely guilty, so with anger, sneers and audible comments they told me to go ahead!” He gave the woman 100 mg of thiamine daily in a pill and she was physiologically cured in six days, sleeping flat and hiking the long halls for exercise to shake off her prolonged immobilization. On the seventh day, because of fetal distress, she was subjected to cesarean section, with the delivery of a 3 lbs. 12 oz. baby with a normal Apgar score.

Yes, I know how many will react to this. They will say that this patient was on a tropical island where beriberi was much more likely. This could not happen in America where the science of nutrition is so well known and where all the foods are enriched with vitamins. Also, they might think that the doctor was deluded into thinking that all forms of toxemia were really beriberi and that he had treated this disease rather than toxemia. So the doctor started the clinic patients on prophylactic mega-thiamine for the second and third trimesters, preventing development of every type of toxemia completely, including eclampsia, preeclampsia intra-uterine growth retardation, premature delivery, fetal death, premature rupture of membranes, placenta previa and gestational diabetes, among other possible complications. Again, the reader might well say that these were all patients on a tropical island. Consider however that this doctor had spent his professional lifetime in his attempt to bring healthy babies into the world. He was conversant with all the complications of pregnancy. Did the island doctors fail to recognize beriberi or is toxemia of pregnancy merely a manifestation of thiamine deficiency? Our preconceived idea that each disease is a separate entity with a separate cause and an individualized treatment may very well be completely wrong. If energy metabolism is compromised, the dysfunctional effects will be related to the cells most affected. The symptoms and physical or mental deterioration will be as variable as the distribution of the energy deficit.

There is a lot more to this and I can only suggest that anybody wishing to be pregnant should obtain this book by John B Irwin M.D. “The Natural Way to a Trouble-Free Pregnancy” with the subtitle “The Toxemia-Thiamine Connection”.

It is, of course, mandatory for you to undertake this with the permission and care of your OB/GYN physician if you are pregnant. However, do not expect that the physician will automatically accept the idea. You may have to show him/her the book. As I have said many times in posts on this website, the emerging truth concerning the application of vitamins in the treatment of disease and the preservation of health has not yet reached the collective psyche of the medical profession. It has been hard won by the few pioneers that have begun to practice what is now called Alternative Complementary Medicine. They use few drugs and the results that they get are real.

Of RDAs and Mega-doses

It is quite obvious that you might ask the question, why, if this is so important in the lives and well-being of millions, it is not an acceptable practice in modern medicine by the majority of physicians? The answer is because of the teaching of biochemistry in medical schools. We all have known for many years that thiamine is acquired from the diet.  The recommended daily allowance (RDA) is 1 to 1.5 mg. This minute dose acts as what is called a cofactor to many enzymes. Without sufficient cofactor, the enzymes do not function properly. Thus, vitamin deficiency has long been regarded as a situation that requires simple replacement of the cofactor. Therefore, the only dose required is that recommended as the RDA and mega-doses are regarded as being completely useless.

Unfortunately, what has not sufficiently been considered is that an overload of simple carbohydrate empty calories overwhelms the ability of thiamine to process  glucose derived from the food. Glucose is used by body cells as fuel and the energy supply that results from it must meet physical and mental demands for maintaining healthy life. The modern diet is grotesquely unnatural and, because of the overload of empty calories the enzymes that are starved of their cofactors, begin to deteriorate. In order to resuscitate them, the cofactors must be used in a pharmacological way to stimulate the respective enzymes back into a healthy state.

Pregnancy Energy Demands are Significant

Pregnancy requires energy for the development of the baby as well as the health of the mother so the demand is greater. Cells will use what is needed of the mega-dose for the resuscitation to take place and will discard the excess in urine. The beauty of this new way of thinking about treatment of disease is that it is non-toxic and harmless. We even know now that some of the diseases, previously thought to be entirely genetic in origin, respond to mega-doses of vitamins. This has opened up a brand-new science called epigenetics that studies the effect of lifestyle and nutrition on genes. Genes are no longer considered to be solely in charge of our health destiny. We each have a responsibility towards the preservation of the blueprint (inheritance) by what we eat and our lifestyles.

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