Could Low Potassium Be Raising Your Blood Sugar?

0:00Could low potassium be making your blood sugar harder to control? You probably know that insulin helps move sugar from your blood into your cells, but it moves potassium into your cells too. And the connection works both ways. Your pancreas needs enough potassium to release insulin properly. When potassium gets too low, it may release less insulin and your blood sugar can rise. Another hormone, called aldosterone, helps control how much potassium you lose through your kidneys. Too much of this hormone can cause you to lose too much potassium, which adds to the problem. Does that mean taking potassium supplements will prevent diabetes?

0:40Well, we don't have the evidence for that, but it does mean potassium deserves a place in the conversation about metabolic health. Start with potassium-rich whole foods and discuss low potassium with your doctor, especially if you have high blood pressure. This is Lecture 167 of The Metabolic Classroom.

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3:28welcome back to the metabolic classroom i'm ben bickman metabolic scientist and professor of cell biology potassium is a mineral that carries a small electrical charge when we have it in our body or when it's dissolved in any solution but that's why it's called an electrolyte and you might be wondering why we're talking about this in the metabolic classroom well Well, it may not surprise you, given what you know about me, that this is relevant. Potassium is relevant in a conversation of insulin or about insulin because insulin is one of the two main hormones that decide where potassium goes. The other hormone is aldosterone.

4:08That's a hormone that comes from the adrenal glands. But these two hormones work together and sometimes in the same direction, sometimes against each other, and potassium in turn affects how well the pancreas works and does one of its famous jobs of producing insulin. Understanding this dynamic and this somewhat complicated relationship can help explain why low potassium can worsen blood sugar control and why even how you end a fast may matter. All of this we'll get to, of course. So to start off, almost all the potassium in your body, about 98%, is actually inside your cells. And most of it's in the muscle.

4:49That's not surprising because the muscle is so much of what makes up our body. But only a very small part of potassium is actually in your blood. So when you get a blood test, what you see in that blood test is about 2 % of the total amount of potassium you have in your body. So the concentration of potassium inside your cell is about 30 times higher than what you have outside. This difference in potassium levels is maintained by a little microscopic pump, which is in the cell's outer surface. It's hooked into the membrane and it uses energy. It uses ATP and it will pump sodium out of the cell while it's pumping potassium in.

5:32And insulin is one of the most important regulators of that pump. Insulin makes the pump work faster, makes it work overtime. It increases the number of pumps in the cell as well. So the result is that potassium moves from the blood into the cell when insulin comes and knocks on the door of the cell. So it's one more of insulin's many effects. The classic human evidence comes from a study that gave people insulin at increasing doses while keeping their blood sugar at a normal fasting level. That's a clamp. So in this study, any change in potassium came from insulin doing something rather than from any change in blood sugar.

6:13And the blood potassium in this study fell further, ever further as the insulin went ever up. So the insulin dose went up in these people while keeping blood sugar normal and the potassium continued to go down. So every time we eat a meal with carbohydrates, insulin rises and moves potassium into the cell. This is useful since a meal will bring in potassium and insulin will help clear it from the blood before the kidneys can get rid of it or before blood potassium levels go too high, which can be problematic in its own right. But it does also mean that blood potassium can drop after a sugary meal or drink, even when the body has plenty of potassium overall because the potassium hasn't left the body.

7:00It's only moved from outside the cells in the blood to inside the cells. That's why a blood potassium result in the body's total potassium can tell two very different stories. And someone can have a normal blood value while their stores of potassium in their whole body are actually going down. This effect of insulin on potassium actually holds up even in insulin resistance. Researchers studied people with and without type 2 diabetes using the CLAMP method I mentioned earlier, so it holds blood sugar steady while measuring how the body is responding to insulin. And insulin's ability to clear blood glucose from the blood was weaker as expected in people with more type 2 diabetes, but insulin's ability to move potassium into the cells was the same in everyone.

7:53Resistance to insulin's effect on blood glucose does not carry over to the effect on potassium. And since insulin is chronically high in insulin resistance, that potassium effect stays active. Now, moving on, the relationship runs the other way because potassium levels shape how much insulin the pancreas releases. In one very well done study, seven healthy young people were made low to have low potassium levels over about a week with a low potassium diet plus a medicine that binds potassium in the gut so that it couldn't be absorbed. CLAMP studies before and after allowed the researchers to measure insulin release separately from how well the body responded to insulin.

8:43And after the potassium loss, the amount of sugar their bodies could clear fell by about a quarter. And so did the amount of insulin they released, while the tissue's response to insulin didn't change. The more potassium they lost, the more their insulin release fell. the insulin making cells of the pancreas those beta cells rely on potassium to send the signal that releases insulin so it makes sense that potassium levels affect insulin release even though the exact details in humans aren't necessarily or fully settled now a follow-up study by that same group looked at water pills that's just kind of a loose name for a a kind of drug that's prescribed for high blood pressure.

9:30And these are known actually to worsen blood sugar control. So once again, they took seven healthy individuals. They took a common water pill for 10 days while their lost potassium was replaced. And with potassium kept normal, the drug changed neither their blood sugar control nor their insulin release. But when potassium was allowed to fall, blood sugar control worsened because the pancreas released less insulin. So the strongest evidence is that low potassium reduces insulin release. And in someone whose blood sugar control depends on high insulin output, a pancreas that can release less insulin will absolutely lead to higher blood sugar levels.

10:14Now let's bring in aldosterone because insulin doesn't manage potassium alone. Aldosterone is made by the adrenal glands. As I mentioned that those are the small little very busy hormone producing glands that sit right above the kidneys or the renal tissue which is where they get their name from the adrenal glands its main job aldosterone is to tell the kidneys to hold on to sodium a different electrolyte and get rid of potassium now the two hormones actually kind of divide the work by timing Insulin acts within minutes, moving potassium into the cells to keep the blood level safe after a meal, while the kidneys take hours to adjust how much potassium will leave in the urine, with aldosterone as one of those main signals.

11:08So that cell effect that insulin can have is very, very quick, but the kidney effect, which is primarily where aldosterone acts, again, that's on the order of hours. and potassium itself can feed back on this system because a rise in blood potassium directly tells the adrenal glands to release more aldosterone and remember that aldosterone wants to get rid of potassium in the kidneys of course the sum of all of this is that we have an improved ability to clear the extra potassium from the kidneys insulin and aldosterone also share a second job, which is holding on to sodium. When researchers raised insulin in healthy people while keeping blood sugar at a normal fasting level, the kidneys cut their sodium output or what they were releasing roughly in half and held on to more potassium too.

12:02And aldosterone stayed low and unchanged the entire time. So insulin tells the kidneys to keep sodium on its own, separately from aldosterone, which means a person with chronically high insulin has two hormones that can each push the kidneys to retain sodium and water. The kidneys response to insulin also appears to stay intact in insulin resistance, much like that potassium effect I mentioned a moment ago. But this, all of this helps us understand one of the primary mechanisms whereby insulin resistance leads to hypertension. This is why when I am asked what is one of the simplest clinical symptoms of insulin resistance, I'm quick to say high blood pressure.

12:48It's such a common driver. And that's one mechanism among many whereby insulin resistance promotes an increased blood pressure. But this is one. And again, to reiterate, when insulin is high, it's telling the kidneys to retain sodium and water. And that with more water in the blood comes a higher blood pressure. Now, back to the water pills. Water pills show how these hormones can kind of get a little tangled. A water pill will make the kidneys release sodium and water. And the body will respond by raising aldosterone to try to hold on to sodium. But that extra aldosterone pushes even more potassium out into the urine.

13:29In a specific study I found, a crossover trial in people with high blood pressure, One of these water pills made the body less responsive to insulin, even with potassium held steady with various supplementation. And adding a specific drug that blocks aldosterone, it prevented this change. So water pills appear to affect blood sugar, both through potassium loss and what that can do to the beta cells, as I mentioned a moment ago, but also through the aldosterone response that they provoke. now let's turn to what happens when aldosterone runs too high that's the clearest example here the clearest example here is a condition where one or both of the adrenal glands just makes too much aldosterone on their own a primary hyper aldosteronism it used to be considered rare but with some careful testing and actually there's evidence to suggest it's a bit more common than we originally thought, affecting roughly one in six people that have mild high blood pressure, and even further, more than one in five who have very severe or very hard to control, poor responding blood pressure, even though many of these people have never been diagnosed.

14:46In a specific study of a little over 300 people with this condition, type 2 diabetes was more common than in similar people from the general population, about 17 % versus 10%. And the lower their potassium, the higher their blood sugar after a glucose tolerance test. Low potassium is part of that story, but aldosterone seems to act on the pancreas more directly as well. In a study of roughly 60 people who had surgery to remove an aldosterone-producing tumor, insulin release went up about a year later even though their insulin sensitivity actually dipped that's not that surprising even though the scientists said it was think about what you know about the main driver of insulin resistance what is it think to yourself it's too much insulin and so if you're now having a medication that's helping the body make more insulin well we would say that's helping control blood sugar but if the body is making more insulin it may also be driving insulin resistance, which is exactly what they found.

15:52Now, that was a human study, and there's only so much you can do in humans. And so as biomedical scientists, we'll sometimes use animal models in order to tease out our understanding a little more. Animal work actually suggests the same effect. Mice that are unable to make aldosterone, they produce much more insulin. And adding aldosterone to like a beta cell culture, you know, a little Petri dish growing beta cells that make insulin, that reduces the insulin they make, even if potassium is normal. So here we have a potassium independent regulation with aldosterone. But remember, aldosterone is really affected by potassium levels.

16:34Nevertheless, excess aldosterone appears to suppress insulin release both by draining potassium, forcing it out of the kidneys into the urine, and by directly acting on the beta cells. Now that's one direction, but the connection also runs from metabolic health back to aldosterone. aldosterone levels tend to be higher in people with obesity and in a study of women with obesity who lost only about five percent of their body weight over three months aldosterone fell by about 30 percent and blood pressure came down no surprise lab studies suggest that fat tissue releases signals that can stimulate the adrenal glands which may help explain that link and it means that the same metabolic state that raises insulin also tends to raise aldosterone, which with both hormones together, we're pushing the kidneys to hold on to more sodium and of course more water.

17:38Now let's shift to everyday life.

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20:05Diet is the most common reason for low potassium in the general public. Potassium comes mainly from whole food sources, vegetables, fruits, lentils, also dairy, meat, and fish. So you're getting it from plant sources and animal sources. Usually a refined source of either of those will lower it compared to maybe a whole food source, even some plants. And of course, certainly from animal sources, that's always a good way to get it. Most American adults eat less potassium than recommended, and a processed refined carbohydrate diet pairs that lower potassium intake with frequent and significant spikes in insulin.

20:51Now, magnesium actually matters too here because when magnesium is low, the kidneys lose more potassium, and potassium can be hard to bring back up until magnesium is corrected. lab values which some of you might be thinking of as you're listening to this you might be referring back to a recent lab test they actually i deserve we should appreciate them and we should look at them they deserve some another look here a normal blood potassium on a standard lab report it will run from about three about three to five in the values there being milliequivalents typically. So a number of about three to five, but risk actually is spread out.

21:37It's significantly impacted across what seems to be an incredibly narrow range. The problem here with potassium is that there's so little in the blood that you would look at that range of say three and a half to five, which is the normal range. If you start to shift that just a little bit, you can appreciate how what looks like an absolute change in terms of that incredibly narrow range of about 1.5 points, 1.5 milliequivalents. Relatively, that's a pretty significant adjustment. To put a fine point on this, in a study that followed more than 12 ,000 adults for about nine years, people in the lower part of that normal range, so it was still considered normal, but they're closer down to that three and a half number.

22:23So they're in that normal range, but on that lower end, they had about 60 % higher risk of developing diabetes than people at the top range, regardless of whether they were on any kind of water pills or other medication. That study followed people over time now, and it didn't test a specific treatment. So it can't prove that raising potassium prevents diabetes, but a result at the low end of normal is worth discussing with your doctor. So if it's not flagged, but especially if you have high blood pressure, or you may have a poor response to an oral glucose tolerance test, all of that suggests that even though your potassium is in a normal range, it might be a little lower than it should be for you.

23:07So you might want to look into that a little more. Let's turn to fasting, something that I know is of great interest to the metabolic classroom attendees or students, if I can call you that because in fasting, insulin and aldosterone move in opposite directions and potassium kind of gets caught in between this custody battle. When you stop eating, insulin falls. And since insulin tells the kidneys to hold on to sodium, low insulin lets the kidneys release more sodium and water, which explains a lot of the very early weight loss. So in the first few days of a fast or a significant reduction in dietary carbs, We all know a lot of that weight loss is just fluid changes.

23:53That early loss of fluid then raises aldosterone because aldosterone will respond to a reduction in blood pressure. So aldosterone, the adrenal glands are sensing this lower blood pressure actually because of the kidneys telling it to, and then aldosterone is going to step in in order to try to correct this. But as aldosterone goes up, as you know now, it's pushing more potassium into the urine. At the same time, the body shifts to burning fat and the liver is making ketones. And ketones, of course, are very, very mildly acidic, especially at those reasonable low levels of just ketosis. But when the kidneys clear the extra ketones, they send sodium and potassium out with them.

24:40So after several days, the kidneys adapt in a pretty clever way. They're making more ammonia to pair with those ketones instead. So the ammonia is kind of acting as a little bit of a buffer and that can spare the body's sodium and potassium. But by the end of a week of fasting, the body can be short, roughly about 12 grams of potassium or about three or four days worth of the recommended intake. Now, let's look at an interesting case study here. The most remarkable example of this comes from Scotland, where in the 1960s, there is a well-documented case of a young man who weighed more than 450 pounds.

25:23Well, he fasted under medical supervision for 382 days, taking only fluids, no calories whatsoever. He wasn't eating any calories. He wasn't drinking any calories. So he just had calorie-free fluids, vitamins, and a few supplements, and he finished this 382 days weighing about 180 pounds. Interestingly, he kept it off and lived a perfectly long, healthy life. But back to potassium. His blood potassium dropped early in the fast, and it needed to be corrected at that early point within just weeks. But after that, it stayed normal for the rest of the year without any supplementation. This just shows us how well the kidneys can adapt once they get past those first few days of the changes and that tug of war between insulin and aldosterone.

26:15Now, most people, you included, I suspect, will never fast anywhere near that long, but it tells us that the riskiest moments for potassium are at the beginning of a fast and at the moment it ends, as I'm going to get to in a moment. so when you end your fast potassium is also very important and can change in some unexpected and unwanted ways but during the fast in order to try to keep the blood levels stable the cells will start giving up some of its potassium most especially muscle so a blood test can look normal even if the overall body level of potassium is starting to go down again but when the fast ends, especially if it ends with a large meal of refined carbohydrate, insulin will rise sharply.

27:06Now think for just a moment before I go on, how do most people want to end a fast? If they've not planned for it, they're usually going to end their fast by eating a lot of refined starches and sugars. But with that significant insulin rise, it starts pushing the potassium into the cells all at once. And that means that the actual blood amount of potassium can get dangerously low. In fact, so low that it can become lethal and the person can start to experience consequences of low potassium, which is dangerous. In fact, it's lethal. This is something in its most serious form called the refeeding syndrome.

27:47It was something that clinicians first recognized after the Second World War when some of the very severely starved prisoners and survivors became very, very ill, including some died after being given ordinary food too quickly. Ordinary food, of course, being high carbohydrate foods. Today, this is something that still can be evidenced in a hospital, but it's more often than people who have been severely malnourished or they've been eating too little or nothing for an extended period of time, including people with, say, eating disorders like anorexia. They're going to have low potassium and that can actually result in a dysrhythmia of the heart.

28:27Essentially, the heart stops beating.

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30:45because of the low potassium so if you're a person who's fasting for multiple days which happens more often these days and i'm fine with that it is worth just keeping in mind a little nagging voice telling you to be wary of the refeeding syndrome where over time your body's adapting your overall potassium in your body is starting to come down total body because the cells are releasing enough potassium to keep blood potassium normal but if you rapidly spike insulin insulin is pushing all that potassium into the back into the cells so the cells get their potassium back, but that low level of potassium in the blood, among its many consequences, is the heart not beating well.

31:32The heart is so sensitive to the electrical signal, the electrolytes, which help drive this, of course. It needs to be finely tuned in order to be contracting normally as you mess with the electrolytes here with this refeeding syndrome. What is a nice normal beating heart starts to become spastic, ultimately potentially killing the person. Now, of course, the great majority of us are fasting for several hours within a day or a single day, maybe a couple days, you're not going to come close to this, but the same hormonal shift will happen, albeit on a smaller scale, whenever a long fast ends with a big insulin spike.

32:10So for anyone who fasts for several days, the way you break your fast needs to be considered as a very important part of the fast. And as I've said before, how you end your fast matters more than how long you fast. So when you're breaking your fast to try to find some application in this lecture, this mini lecture, start with a modest meal, focus on proteins and the fats that come with it. This is eggs, meat, fish. And if you want some vegetables, make sure you're selecting fruits or you want plants, carbohydrates go with those that are on the lower glycemic load end. All these foods are not only going to bring potassium with them, but that relatively lower amount of glucose load means a smaller insulin load, which just gives your body a little time to adjust back to normal potassium.

33:01Maybe, of course, you're taking in some salt with some potassium there during that time as well. Many fasting electrolyte mixes do have some potassium and that's going to be fine for most people. But if you've got kidney disease or blood pressure medications, then you just need to always be a little more, you need to consider this more carefully than someone else would. Anyone who takes a water pill or again, the blood pressure medications, or if you take insulin as an insulin therapy, you just need to be mindful of some of these changes a little more than someone else. low carbohydrate diets produce a much more modest version of the same early shift that I'd mentioned with fasting with regards to potassium changes.

33:47And that's why some of the lightheadedness and the headache, even some of the cramps that people may feel as they're adapting to a low carb ketogenic diet, it's usually a response to this modest shift in electrolytes, which is why so commonly people will say to get through that keto flu or that keto adaptation phase, make sure you're staying hydrated with electrolytes. Finally, let's bring this whole mini lecture together. Insulin moves potassium into cells within minutes, and it keeps doing so even in insulin resistance, while aldosterone and the kidneys decide over several hours how much of that potassium the body is going to hold on to.

34:31Both hormones tell the kidneys to hold on to sodium, and the metabolic state that raises insulin tends to raise aldosterone as well. Low potassium, in turn, reduces insulin release, and excess aldosterone appears to suppress insulin release, both by draining the potassium from the body and by acting on the pancreas directly. Insulin's effect on where potassium goes is well established, while the evidence on low potassium and aldosterone reducing insulin release comes from some smaller human studies and, of course, from some complementary animal work. But there's not really been any large trial yet that has shown that raising potassium can meaningfully prevent diabetes.

35:19Having said that, let me just extrapolate for a moment where in some ethnicities, specifically East Asians, like Japanese and Chinese ethnicities, those are ethnicities known to generally produce less insulin, which is largely why they have higher blood glucose levels or blood sugar levels and are so much more readily diagnosed with type 2 diabetes. I can't help but wonder to what degree might certain ethnicities need potassium more than others. For most people with healthy kidneys, The practical steps are just to eat real foods, including potassium rich foods. And if there's any concern here based on medications or blood pressure changes, of course, talk to your clinician.

36:05I'm just your friendly neighborhood scientist. Then as a reminder, when it comes to multi-day fasts, be smart with how you end that fast. When you break it, break it with foods that aren't, my suggestion is that won't raise your insulin significantly so that you can avoid even a modest version of that refeeding syndrome. Class dismissed. Until next time, more knowledge, better health.

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