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RHR: A Functional Medicine Approach to PCOS


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Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 5 to 15 percent of women. Even though it is the most common form of hormone imbalance, conventional medicine has had little success in treating it. Today I’m talking with Dr. Amy Nett about the Functional Medicine approach to PCOS and how it differs from the conventional model.

Revolution Health Radio podcast, Chris Kresser

In this episode we discuss:

  • Dr. Nett’s transition from conventional to Functional Medicine
  • What is polycystic ovary syndrome?
  • Addressing underlying causes
  • How useful is a diagnosis of PCOS?
  • Treatment of PCOS

Chris Kresser: Hey, everybody, it’s Chris. Welcome to another episode of Revolution Health Radio.

This week I have a special guest, Dr. Amy Nett, who works with me at California Center for Functional Medicine and is also on the Kresser Institute faculty and helps me teach the ADAPT practitioner training program.

Amy how long have you been with us now at CCFM? I don’t remember the exact month that you joined?

Dr. Amy Nett: Well, I think you and I started working together even before CCFM was officially in existence, so over three years now I think.

Chris: Wow, time flies. I mean it seems like you’ve been there forever. It’s amazing how far we’ve come in that last three years. It tripled in size, I think, in three years, in terms of staff and growth.

Amy: Absolutely, and then watching that clinician training program, watching you develop that from the ground up and seeing that grow has been really exciting too, so you’ve been busy.

Chris: Definitely. We’ve all been busy. It’s been fun, a great ride. Before we dive into today’s topic, which I’m really excited about, we’re going to talk about PCOS, and you pointed out to me that I really haven’t written that much about this topic or spoken about it, which surprised me because it’s such a big concern for women, and it’s something that in my mind I thought I had covered, but I hadn’t, so we’re going to dive into that today. But before we do that, given that it’s been three years now, and so now you have a lot more experience in Functional Medicine, you’re helping me teach in the Kresser Institute, but you didn’t come from a Functional Medicine background, you came from radiology and practicing within the conventional system, I’m sure some of the listeners, particularly practitioners, would be curious how that transition has been for you now looking back to where you were five years ago and where you are now and what that’s been like for you both professionally and personally.

Addressing the root causes of PCOS.

Dr. Nett’s Transition from Conventional to Functional Medicine

Amy: Yes. As you said, I’ve trained in a very conventional medical setting at Georgetown University Medical School and then Stanford University for radiology, both residency and then also fellowship in diagnostic radiology. We talked about, last time I was on the podcast, I think, the first time I was on the podcast quite a few years ago, that it didn’t align with my values and it also didn’t work for me when I was having my own health issues, so being able to work in the Functional Medicine setting, I think all of us thrive a lot more when our work is actually in alignment with our own values and beliefs. It’s great to be able to work with something that I’m passionate about and being able to share these things with patients and learn from my patients. I mean, you know a lot of our patients are so educated and well read, and they’re sifting through things, that I love it when patients bring something new to us that we get to dive into and learn about.

Chris: Absolutely. I’ve always said my patients are my greatest teachers.

Amy: Yes.

Chris: As long as we’re open to the case. It has always blown me away that the attitude of some physicians and clinicians is like … we both had the experience of patients coming in telling us that they’ve been excited about something and gone to their doctor only to see the eye roll or the shaking of the head, so you stop doing Google research, and to some extent I get that, but as a practitioner myself, I get really excited when I hear about something I didn’t already know about because Functional Medicine is extremely effective and powerful, but with the complexity of patients that we see, I’m eager to learn about any new thing that could help that I possibly can.

Amy: Yes, I agree. Again, having come from a more conventional background, I was used to this approach of using medications and looking for really clear treatments, and then from you I learned more about herbal approaches, but then we have these really sensitive patients, and we’re realizing that we need to find different ways to work with symptoms, that it’s not just supplements and medications, that it can be … you and I have both gotten into this DNRS program, like a limbic system healing. I mean, these are things that I wouldn’t have considered five years ago.

Chris: It wasn’t part of your radiology residency at Stanford, was it?

Amy:  No. I think that would have gotten some eye rolling.

Chris: Yes. But the thing is, there’s actually, maybe not directly with this particular methodology, but there’s tons of research showing how mindfulness-based stress reduction or mindfulness in general can benefit all kinds of conditions, and when we understand basic physiology of the nervous system and how the psychoneuroendocrinology system, or psychoneuroendocrinology immunology, as we call it, basically that term is trying to say it’s all connected. The nervous system plays such a huge role in every aspect of health, and if we’re running around like a chicken with our head cut off all day, it’s not just going to affect our brain and our nervous system. It’s going to affect every aspect of our health and well-being. Certainly, the more experience I get as a practitioner, the more I keep coming back to the basics. It’s easy to forget that. We have all these powerful Functional Medicine tests and tools, it’s easy to go down those rabbit holes and not pay enough attention to the basics.

Amy: Yes, absolutely. And you know, for better or worse, the body is so interconnected, and once one system gets out of balance, the rest will fall.

Chris: Yes, absolutely. That’s probably a good segue into the topic, because PCOS is multisystem illness, and stress certainly plays a role. I’m sure we’ll be talking a little bit about that. But why don’t we just begin with the basics because I think there’s some misunderstanding about PCOS, and let’s just start with what it is, what defines it, what we know and don’t know about it, and go from there.

What Is Polycystic Ovary Syndrome?

Amy: Yes, absolutely. There’s still a lot we don’t know about it. PCOS, or polycystic ovary syndrome, basically is a metabolic disorder with hormonal imbalances. It’s actually the most common form of hormonal imbalance. We would also call this an endocrine disorder, “endocrine” just referring to hormones, so an endocrine disorder, the most common one in women of reproductive age, probably affecting somewhere between about 5 to 15 percent of women. There are some controversies around the diagnostic criteria. There are different ways to make the diagnosis, so I think that’s one of the reasons we don’t have a clear idea on exactly how many women this is affecting. The main hormone disruption that we’re seeing in PCOS, or polycystic ovary syndrome, is higher-than-normal levels of androgens in women. Androgens, you can think of as the “male hormones.” These are things like testosterone, DHEA, and these hormones are responsible for giving some of the male characteristics. As women we normally have these hormones, but in PCOS we tend to see higher levels of the androgens.

Chris: It’s probably good to point, just to jump in here, the syndrome … It’s interesting about syndromes like irritable bowel syndrome, fibromyalgia syndrome, premenstrual tension syndrome, they’re different than diseases which tend to have either a clearly defined etiology, single known cause or pathological mechanisms we understand, whereas with something like PCOS or any of those other syndromes, it’s more like a description of a clinical picture, right? Signs and symptoms that are common, so we can actually group them together and see it, but we don’t really know what necessarily, what the driving mechanisms are. We have ideas, but we’re not sure.

Amy: Yes, absolutely. And the research just suggesting that there’s probably a lot of different factors that go into polycystic ovary syndrome. Some of it is going to be a genetic predisposition. Some are going to be environmental, and then diet and lifestyle may affect how the syndrome, like you said, the signs and the symptoms actually manifest.

Chris: Right. So they’ve got higher levels of androgens, and then of course insulin and blood sugar. Let’s talk a little bit about that.

Amy: Yes. So similarly, again, we’re seeing this as a metabolic disorder. So we’re seeing higher than normal levels of insulin, and this often goes along with insulin resistance. And so when you have insulin resistance, which is common in diabetics, so we’re normally talking about insulin resistance on the pathway of developing type 2 diabetes or in the setting of diabetes, so we’re also going to see high blood sugar in the setting of insulin resistance. But the most common thing that normally brings it to our attention is actually absent or infrequent periods, again due to the hormonal imbalance that we’re seeing.

Chris: That’s a common complaint amongst women that I see, and I know you see in your practice, and certainly stress seems to play a pretty big role there with women who are not eating enough calories to support their activity level or burning the candle at both ends. I completely agree with you that this is probably a complex multifactorial syndrome that actually has different etiologies and different patients depending on their unique blueprint.

Amy: Yes. Which makes it a little bit more difficult to diagnose and treat, but certainly whenever I have a woman coming in with either what we call amenorrhea, so not having menstrual cycles, or oligomenorrhea, where you have infrequent menstrual cycles, I think this is something that we want to consider. The other way this can present is infertility or even subfertility, so just a difficult time trying to conceive.

Chris: Yes. And then those skin problems are very common, often connected to the androgens or other hormonal imbalance, of course, and excess hair growth or even the opposite, hair falling out, alopecia, which can also be a consequence of excess androgens. Here’s a key difference between Functional and the conventional medicine approach here, with a syndrome like this, and we can use IBS as an analogue. Irritable bowel syndrome in conventional medicine, you go to the doctor, you describe your symptoms, they in turn give you a diagnosis that essentially summarizes your symptoms, your bowel is irritable, you have irritable bowel syndrome, and then the treatments are basically all oriented around managing the symptoms. If there is pain, you might have an analgesic. If there is constipation, you might get a promotility drug for this diarrhea, you might get an anti-diarrheal, and that’s the basic approach. But in Functional Medicine, where that’s obviously not what we’re doing, we’re trying to address the root causes and the underlying mechanisms that contribute, so talk about that in the context of PCOS. What is the best way of addressing this from a Functional point of view or even thinking about it?

Amy: Yes. We need to think about then how was the diagnosis made? Because you’ve just listed quite a few symptoms, and then the thing that you and I haven’t even mentioned yet is polycystic ovaries, which is actually the name of the condition. That part is a little bit confusing because I’ve actually had patients come into my office and say, “Oh, I have PCOS.” And I say, “Okay. How was that diagnosis made?” And they say, “Well, an ultrasound.” Initially one of the common features in polycystic ovary syndrome was an appearance of polycystic ovaries. Technically, they aren’t actually ovarian cysts, they’re actually follicles that were seen, and then they have a very classic appearance in the setting of typical PCOS. But that actually isn’t even used as diagnostic criteria, but it’s something worth mentioning because that’s where the name comes from, polycystic ovary syndrome. But basically, clinically, I’m going to be using all of the information that you and I just mentioned. I’m going to be looking for absent menstrual periods, maybe that excess facial hair growth you mentioned, or hirsutism, thinning of hair on the scalp and along the temples, maybe obesity, insulin resistance, and then I’m going to want to measure the androgen level, those sex hormone levels of testosterone, DHEA. I sometimes will look at the appearance of the ovaries, but the most classic criteria are really just, are there high androgens and is there absent periods, or at least what we call anovulatory periods? You might have bleeding, but it’s not ovulating or producing an egg, which would allow for pregnancy, which is where we see that fertility issue coming up.

Chris: I think the key thing to point out here is when we’re looking at this functionally, we’re not just thinking about how we’re going to deal with the symptoms, but actually trying to identify what the mechanisms are, which is what we’re speaking to, and then address those mechanisms because we know that’s the only chance we have in actually reversing the condition, rather than just helping somebody to live with it. Both of those goals are sometimes are necessary, but it’s just a different approach to how we’re going to get to that goal. In other words, are we going to help people live with the symptoms by addressing the causes or by just suppressing the symptoms?

Addressing Underlying Causes

Amy: Right. You and I are both going to use that standard Functional Medicine approach where someone comes in, they’re complaining of any of these symptoms that we just mentioned. We think about PCOS as a diagnosis, and then the question is, what is causing some of these imbalances? You and I are probably going to have patients come in to us already on a Paleo diet, grain-free, maybe dairy-free diet and there is some interesting research at UCSF that’s ongoing. There’s a study that started in 2015. I think expected completion is in 2020, where they’re looking at a Paleo diet as a treatment approach for women with PCOS. Certainly once we have someone on a Paleo diet, once that piece is handled, we’re still going to want to look at a really comprehensive blood panel. I’m going to want to look at some nutrient levels on that including vitamin D, B vitamins. I’m going to want to look at thyroid function on a comprehensive blood panel, and then we’ll also do gastrointestinal testing, so that’s going to be stool testing, SIBO breath testing. I might also consider heavy metal testing. Also, non-heavy metal toxic burden testing, looking for toxins that might come from plastics manufacturing or from petrochemicals, these toxins in the environment that are fairly ubiquitous and we’re exposed to on a daily basis because some of these toxins, heavy metals included, are endocrine disrupters or hormone disruptors.

Chris: Absolutely. Unfortunately, they’re ubiquitous in the environment and I think we already have a lot of research suggesting harm. But I think that’s only going to increase as we gain more understanding because we’ve already learned that some of our concepts for how toxicity works are really outdated. We know, for example, that a low dose of a toxin can have a completely different effect than a higher dose of that toxin, and that explains why the low dose effects of toxins were missed in studies for so long, because they were just looking for the same type of effects that happen at the high dose and they weren’t seeing those, so they assume that the low dose was safe. But now we know that the low dose can cause completely different and sometimes even opposite effects, so they’ve gone back and started studying these toxins again at lower doses and they’re finding that things like BPA, for example, can cause a lot of harm even at lower doses than most of us are exposed to. I think that’s going to be a bigger part of the story as we go forward. Let’s talk a little bit about the thyroid function and cortisone, and we started by saying that we’ve both come to realize that regulating the nervous system is really crucial and not surprisingly plays a role here.

Amy: Yes. And you’ve talked a lot on prior podcasts and also written on the blog a lot about the HPA axis, the hypothalamic–pituitary–adrenal axis. As we said at the beginning, sort of for better or worse, the body’s incredibly complicated, so the HPA axis could actually more thoroughly be thought of as the HPTAG axis, so that’s the hypothalamic–pituitary–thyroid–adrenal–gonadal, in this case ovarian, axis, but so the thyroid, the adrenals, and the ovaries all have this sort of interconnectedness or communication. I don’t know of any strong evidence showing that thyroid or adrenal dysfunction directly causes PCOS, but I’ve seen so many times that correcting thyroid and adrenal issues improves menstrual cycles and improves those symptoms that are otherwise consistent with PCOS.

Chris: Right. And we have tons of research connecting high and dysregulated cortisol with insulin resistance. We know that high cortisol causes all kinds of cellular resistance, including to thyroid hormone. We know that a disrupted HPA axis can reduce signaling across the board for all the different hormones, so to me … I mean, this is one of the interesting things I think about Functional Medicine research is we often hear claims like, “Oh, there’s no research to support Functional Medicine.” Well, you can’t really do research on Functional Medicine per se. Functional Medicine is just a way of looking at things. It’s a systems approach, and so if we say that a primary tenet of Functional Medicine is that we look for the root causes and underlying mechanisms of disease, then you go into the scientific literature and you say, “Okay, is there any is research that links the HPA axis dysfunction to any of the mechanisms that we suspect cause PCOS?” And then when you do that, sure, there is tons of research. It’s interesting to me how we have to … it’s such a paradigm shift. We have to be continually revising our way of talking about it, and you know this and I know this, but I think a lot of people who are looking at Functional Medicine from the outside and who haven’t really embraced that paradigm, they don’t think about it that way.

Amy: Yes, it’s true, and I think the other thing from what you’re saying in terms of these connections, the other thing is I would be reluctant to make a firm diagnosis of PCOS if there is thyroid or adrenal dysfunction that I would want to correct those before sort of coming down on that diagnosis.

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How Useful Is a Diagnosis of PCOS?

Chris: Right. And especially because it’s kind of … like most syndromes, it’s in some ways a diagnosis of exclusion. Now, you’re eliminating other things that could explain those more straightforward diseases or pathologies that are more clearly defined, and if you can’t do that, then the signs and symptoms left over fall into that bucket of PCR. I guess that leads to the next question which is, how useful is the diagnosis of PCOS, especially if it’s from a Functional Medicine perspective? In the conventional model, not to sound like too much of a cynic here, but in some cases, the usefulness of a diagnosis is primarily related to the drug company making more money selling drugs for that condition. We know that, like in the case of Viagra, erectile dysfunction, an advertising agency made up erectile dysfunction, or ED, as a condition as a way of selling more of our Viagra, which was an accident. Viagra was discovered during the development of a different drug, and they just happened to notice that it was having this other effect, and then they created this whole syndrome called “erectile dysfunction” to drive selling that drug, but in Functional Medicine that’s not how we approach things. So is PCOS even useful from a Functional perspective?

Amy:  I don’t know. I actually don’t really find it all that useful of a term. I find that individual components are helpful in the sense that if there is insulin resistance, I want to identify that and correct it. If there is anovulation, I want to identify what’s causing the hormonal imbalance. But no, I don’t really think that PCOS is a particularly helpful term in the Functional Medicine setting, and then this is in part because, as you said, it’s a syndrome. It’s a collection of signs and symptoms that we put together in a pattern and then put a label on, but there is such a wide spectrum of how women actually present, how this manifests, and the causes. So I’m treating each of my “PCOS” patients differently based on their individual physiology.

Chris: Right, yes. It might be useful in the sense that someone who has it can come in and say to you or me, “I’ve got PCOS. I’ve been diagnosed with PCOS” and then you and I immediately have a sense of what they’re dealing with. It maybe shortens the conversation a little bit, but I agree. It’s not necessarily useful outside of that context. Nevertheless, let’s talk about how it is diagnosed just so that people understand what defines this syndrome from a conventional perspective? I think there are three criteria that have to be satisfied.

Amy: In the medical literature, there are a few different criteria and a few different ways that PCOS is defined. There is not a uniform, agreed-upon diagnosis, but I think the most common combination is having, number one, high androgens, so again, those sex hormones like testosterone, DHEA. Number two would be anovulation, or absent ovulation, and again this is why we tend to see irregular menstrual cycles. I want to quickly add here that a normal menstrual cycle can actually be anywhere from about 21 to 35 days. I have a lot of women who come in and say, yes, I have irregular cycles. They are 24 to 30 days. That’s completely normal. Most of us are not clockwork 28 days. It’s only about 10 to 15 percent of women who really have that clockwork 28-day cycle. I’m looking most often for cycles that are longer than 35 days. And then the third criteria that again, isn’t necessary to make a diagnosis but is having a polycystic ovary appearance on ultrasound imaging. But again, I don’t find this the most useful, and again, partly some women who have polycystic ovaries actually don’t have any of these other symptoms. This is why we think, well maybe there’s a genetic or epigenetic predisposition towards PCOS and these women who have a polycystic ovary appearance but don’t otherwise have manifestations of this syndrome are just managing this with diet and lifestyle.

Chris: Right. When we think about diagnosis, all the caveats we’ve already discussed included, what else do we want to consider and look at, given that we know what these various mechanisms are that are involved? What else are you looking at in patients from a testing perspective?

Amy: One of the most important things I’m going to be looking at is the blood sugar marker, so I’m going to be looking at insulin resistance, so I want a blood panel that’s going to include glucose, hemoglobin A1c, a fasting insulin level. I might look at fructosamine level also, and then because PCOS and insulin resistance can also be associated with metabolic syndrome, which can be associated with high cholesterol and increased cardiovascular disease risk, I’m also going to want to check at least a basic lipid or cholesterol profile on my patients, and then we may or may not get into some of those more advanced cardiovascular disease markers like LDL particle number.

Chris: Yes, all of that. All of the basic tests that we run on pretty much every patient that comes through the door. All of the GI testing, the blood panels, nutrients, and then maybe heavy metals and other toxins, depending on their exposure.

Amy: Right.

Treatment of PCOS

Chris: So let’s talk a little bit about treatment. Obviously, this will depend. I mean, this is another big difference in conventional and Functional Medicine. In conventional medicine, usually it is three minutes focused on the disease, so different patients with the same disease will get the same treatment, whereas in Functional Medicine, we treat the patient rather than the disease, and I think PCOS is a fantastic example of why that’s necessary. Why don’t you say a little bit more about that in that context?

Amy: Yes. Well, this is a little bit painful because unfortunately, most women with irregular periods who go in to see their conventional Western medical doctor are probably going to be given an oral contraceptive pill to “normalize” for cycle. We could have a separate podcast on an oral contraceptive pill. The bottom line here, I’m not a fan. I wouldn’t recommend these. Oral contraceptives don’t address any of the underlying causes associated with PCOS or lower the risks that are associated with PCOS, like the blood sugar imbalance or the decreased fertility. It’s true that oral contraceptive pills do cause regular vaginal bleeding, but it’s really important to know that that’s not a period. It’s just bleeding that’s induced by the combination of estrogen and synthetic progestin in the pill. We’ll leave that for another day, but oral contraceptive pills are used in conventional medicine really to mask or hide the symptoms of PCOS. That’s your conventional treatment, but from a Functional Medicine perspective, we’re going to want to come back to all of the test results that we just talked about running. So the gut testing, the comprehensive blood panel, the heavy metal burden, the non-heavy metal toxic burden because we want to look at anything that could be contributing to hormonal disruption, immune imbalance, chronic inflammation.

Chris: Right. For one woman, it might be primarily an issue of insulin resistance and metabolic dysfunction and so for her, the treatment, it might be low-carb or a ketogenic type of diet, intermittent fasting, and other interventions to regulate blood sugar, whereas for somebody else, if you do some testing and you find, “Wow, you’ve got SIBO and you’ve also got pretty significant mercury toxicity complicated by high levels of arsenic and lead,” then maybe those are going to be the primary focus to begin with.

Amy: Yes. We’re going to use all of those tests, but we did to try to tailor the treatment approach. To each patient, it’s going to look a little bit different. I mean there are some basic nutrients that we will want to think about in terms of supporting just regular menstrual cycles, some that can be a little bit more targeted to PCOS, but diet and exercise are just top of the list in addressing these symptoms.

Chris: Cool. Let’s talk a little bit more about the whole spectrum of treatment options. If we were to rank them in terms of importance, what would you say is at the top of your list? And go from there.

Amy: I’m going to stick with diet and exercise as the two most important pieces in terms of addressing PCOS.

Chris: Oh, geez, Amy. That’s so boring.

Amy: I know it is.

Chris: Can’t you be more original?

Amy: I know it is.

Chris: Always back to the basics, isn’t it?

Amy: It is always back to the basics, and it sounds like you tend to go also towards like a lower-carbohydrate and sometimes ketogenic diet with women.

Chris: It depends on the situation. If a woman is obese and severely insulin resistant and her HPA axis is in pretty good shape, then yes, but if she is not significantly overweight and there’s not a lot of metabolic dysfunction and she’s burning the candle at both ends and working and has young kids at home and is doing CrossFit … circadian disruption, I’m not going to do that because generally that doesn’t go well in that, so it’s super, super individualized at that point.

Amy: Yes, I agree. For PCOS, I’m probably going to go either moderate-carb or maybe low-carb, and rarely ketogenic. I don’t love doing ketogenic diets in women long term. Short-term therapeutic, yes, but not seeing the most benefit with ketogenic long term.

Chris: Yes. So how about physical activity and exercise? What are you seeing in your patients with that? Because most of our patients are not the typical patients, they’re people who tend to be already a little bit more on the ball with this kind of thing. So, what are you finding is helpful?

Amy: I use exercise most. The reason I recommend it in this setting is because it really improves insulin sensitivity, which is thought to be one of the driving factors in at least some cases of PCOS. So when patients ask … and the other issue we talked about, adrenals, because a lot of patients come in under the impression of, “Oh, I have some degree of adrenal dysregulation, therefore I shouldn’t exercise,” but I haven’t seen that and I still think that exercise is really important. You might have to moderate. It might not be CrossFit five times a week, but even moderate strength training, resistance exercise, I think is well tolerated, even with moderate HPA axis and may even improve some of that HPA axis. And so, I think doing anything you enjoy and doing exercise to the degree that it leaves you feeling refreshed and better rather than depleted.

Chris: What about diet in terms of, as you said, moderate-carb or low-carb, but what else? Anything particular in the diet from the research or just your experience with PCOS?

Amy: Well, and then just to clarify, I’m sure all of your listeners know, but of course we’re talking about this within a Paleo context, so grain-free and dairy-free, particularly. We said acne is really common in PCOS, and they see that dairy is a really common trigger for acne. I think dairy has to be out for at least 30 to 60 days strictly before we even consider reintroducing that and then maybe a full-fat dairy can fit in there. The other thing that I like is intermittent fasting because again, it improves insulin sensitivity. It can also improve the lipid profile, but as you mentioned, we do have to look for adrenal dysregulation because intermittent fasting is also a mild form of stress on the body.

Chris: Yes for sure. The devil’s in the details, as they say. I’ve seen some research suggesting higher fiber intake, soluble fiber, non-starch polysaccharides, and resistant starches could be helpful here, and that may be through the connection with the gut flora, and it may also be due to the impact it has on insulin levels and blood sugar. We know that fiber intake can significantly affect blood sugar and glucose sensitivity in some people.

Amy: Yes.

Chris: Another thing to just keep in mind because sometimes when people hear low-carb, they end up going low-fiber too, and that’s generally not a good idea, especially with this condition.

Amy: Yes, I agree. I think, given if you’re doing a low-carbohydrate diet, you can still use prebiotic supplements, which is the other way to get around that.

Chris: Absolutely or some combination. All right. What about supplements or nutrients that have been shown to be depleted or beneficial to use with PCOS?

Amy: Yes. I think the number-one nutrient that I would put on top of my wish list if I have to prioritize supplements for a patient would be magnesium, in particular magnesium glycinate, is something I recommend for almost all of my patients and certainly any of my female patients with menstrual irregularities. It’s difficult to obtain adequate magnesium through diet alone and it plays such an important role in improving the functions of insulin, leptin, thyroid hormones. It’s essential in the production of estrogens and progesterone. It can also be calming on the nervous system.

Chris: It’s definitely something I’ve talked a lot about because if you look at the symptoms of magnesium deficiency, they are the symptoms that are extremely common. Of course that doesn’t mean that … correlation and not causation. You and I have both seen how often magnesium alone can make a huge difference for somebody. It makes a big difference, too, what type is used and what form. A lot of the magnesium oxides that are typically used in multis or over-the-counter supplements is not very well absorbed and can bring a lot of water into the bowel which can cause that loose stools or diarrhea that some people experience from it. That generally means that it’s not really being absorbed very well, so just keep that in mind when you think about magnesium. Vitamin D is always a discussion when it comes to hormone regulation and immune function. What about that with PCOS?

Amy: As you mentioned, vitamin D actually is more like a hormone than a vitamin and really important in hormonal and also immune balance and immune function. With vitamin D though, I like to check a blood level before starting someone on a vitamin D supplement. I feel pretty safe just recommending a magnesium glycinate supplement around maybe 400 milligrams daily with dinner, but vitamin D, I want to see a blood level before making a dosing recommendation because this is a fat-soluble vitamin, so the levels will potentially build up and accumulate. There’s a pretty wide variety, or wide range, in terms of the amount of vitamin D supplement that people need.

Chris: Absolutely. We both see people. I just had a patient last week who is at 100, and this previous doctor had … or, I think, a book that he had read had suggested that everyone should drive their level up to 110, which just made me so angry. Heart disease is the number-one killer; high levels of vitamin D drop calcium into your arteries and stiffen them and put you at high risk for heart disease, so that’s a really, really bad idea, and yet that idea is still out there so much. It’s like “the more is better” thing. It’s crazy.

Amy: Yes. That’s true. If you have a patient who needs to supplement with higher levels of vitamin D or if someone listening is supplementing with higher levels, maybe more than 5,000 IU daily, I’ll include vitamin K2 in there as well to help with getting calcium to the bones rather than depositing them in the arteries.

Chris: Absolutely. The synergy of all of the fat-soluble vitamins is super important, and we know that taking both vitamin A and K2 in particular raise the toxicity threshold of vitamin D and vice versa. Taking vitamin D and K2 dramatically increases the toxicity threshold of vitamin A, so it’s really good to have all those coming in and that’s why we love cod liver oil so much since you get both, not the K2, but the A and D. Zinc is another nutrient that has a really interesting role in women’s health, both men and women, but I see a lot of zinc deficiency in women. Let’s talk about that a little bit.

Amy: Yes. And again, zinc is one of those nutrients that if someone comes with irregular menstrual cycles, whether it’s PCOS or not, I’m probably going to start them on something like at least 30 milligrams of zinc. Again, I might look at a blood level. Testing zinc levels isn’t quite as straightforward as testing vitamin D levels–and even that isn’t all too straightforward.

Chris: Yes.

Amy: But zinc is pretty important. It helps with supporting the normal menstrual cycle and in particular in the setting of PCOS, zinc plays a really important role in ovarian follicle development. We said that’s one of the primary issues with PCOS is we don’t see normal follicle development, and that’s how you get production of the egg and ability to conceive. Animal products are some of the best sources of zinc, so this is going to be even more common in vegetarians. The other thing is if women, especially if someone’s coming to you with a diagnosis of PCOS, maybe she was put on oral contraceptive pills and then has come in for a Functional Medicine take on things, oral contraceptive pills can deplete zinc as well. That could actually exacerbate the PCOS signs and symptoms.

Chris: Certainly. I’ve had some interesting discussions with Chris Masterjohn recently about zinc, and when it comes to nutritional sciences, usually the smartest guy in the room and has done really deep dives with all these nutrients. He’s come to the idea that for women, in particular, that zinc should be 90 or 100 for optimal function. I regularly see women with zinc in the 50s and 60s, I don’t know about you, Amy, and just getting that level up makes a really big difference. But it’s important to do it the right way, not to take a high dose of zinc forever and ever. Just like vitamin D, that can be problematic because zinc suppresses copper and can actually induce a copper deficiency over time, so definitely something to be aware of. Just because your zinc is in the “normal” lab reference range doesn’t mean you have enough of it.

All right. I’m thinking we should talk B vitamins. If we’re in the discussion about hormones and detoxification of hormones, we need to talk about B vitamins.

Amy: Yes. And again, when we do the comprehensive blood panel that you and I do with all of our new patients, we get quite a few different markers on that blood panel that give us an idea as to whether or not B vitamins are adequate. You and I also both often do a urine organic acids test, which gives us even more markers to know whether or not B vitamins are sufficient. And so, the things that I’m going to look at in particular on the comprehensive blood panel, I’m going to look at the serum levels or the blood levels of B12 and folate. I’m also going to look at homocysteine, methylmalonic acid, and MCV, or mean corpuscular volume, which is the size of the red blood cells. If any of these markers are off, I’m going to think about using active forms of B12 or folate, and I might use just a B-complex vitamin because we know that we need these B vitamins for our detoxification process. This is somewhat dependent on something called methylation, which you and I have done a podcast on before, but we need to make sure that the body is normally clearing these hormones out as well.

Chris: Absolutely. We’ve talked about diet and exercise as being crucial. We talked about addressing all of these other root cause mechanisms, and then we’ve talked about nutrients like zinc, magnesium, vitamin D, B vitamins. So what about specific botanicals or nutrients, nutraceuticals, that are targeted more towards altering hormone balance? Sometimes when we address all those other things that we just talked about, you get 100 percent improvement. Other times there is still some lingering dysfunction imbalance that we need to address. So what then?

Amy: Yes. Inositol is actually one of my favorite supplements to use in a PCOS patient, and I’ll even start a woman on inositol while we’re working on all of these other pieces. If we know that she has … basically, we’re sort of working under the diagnosis of PCOS, again we said a sort of questionable utility to make this diagnosis, but inositol, it’s a chemical compound in the body. It looks a little bit like glucose. There are several different forms of inositol. The two most common are called myo-inositol and D-chiro-inositol. Myo-inositol is the predominant form of inositol in our bodies, and there have actually been some review articles that were published recently, one published in 2016 that looked just at randomized controlled trials of myo-inositol and D-chiro-inositol, and it showed that myo-inositol alone helps to improve insulin sensitivity and also supports normal follicle development. It seems to address both the sex hormone imbalance to some extent and also improve the insulin sensitivity, so two of the primary drivers in PCOS. The role of D-chiro-inositol is a little bit more controversial, but again some of these studies looking at these review articles suggest that myo-inositol and D-chiro-inositol in a physiological ratio of about 40 to 1 may more quickly restore than normal hormonal and metabolic parameters, at least in overweight women with that diagnosis of PCOS.

Chris: Yes. I’ve definitely seen a lot of women benefit from that and this actually highlights an important point too. Now we talk in Functional Medicine about the importance of addressing the root cause, and that’s definitely true, but if we think of this as like a tree with roots and then a trunk and branches, yes, we want to look at the roots and ultimately address those roots because that’s the best way to create lasting change. But that doesn’t mean we can’t also address the branches, and the more troublesome the symptoms are and the more they interfere with the patient’s life, the more necessary it is to sometimes give the patients some immediate relief with something like this. Because in some cases the symptoms can be so challenging that they actually themselves can become an underlying cause or contribute to an underlying cause. For example, if someone is in so much pain or they’re so inflamed that they’re not able to sleep, then that sleep deprivation becomes an underlying cause in itself. It perpetuates the condition, and so in that situation, using something that can reduce the pain and inflammation and help the patient sleep, even though those are kind of symptomatic interventions, is actually useful and part of the whole framework of Functional Medicine.

Amy: Yes. And inositol, I mean again, because we think that two of the potential underlying factors driving PCOS are the sex hormone imbalance and the insulin resistance, here is something that is potentially correcting or restoring both of those parameters.

Chris: There are always different approaches to use depending on where the patient is and what they need most. And then of course there are other things that depend more on the specific mechanism, so I know sometimes we use berberine or other botanicals that can have an effect on blood sugar.

Amy: Berberine is another good one because it does improve insulin sensitivity. It upregulates insulin receptors and stimulates glucose uptake into the cells and might also improve acne, which is another really common complaint in PCOS. But with berberine, I do have some caution in using it long term because it has antimicrobial properties. We really want to think about the pros and cons in terms of using berberine long term and we may decide that there is value to using it to improve the insulin sensitivity and blood sugar levels, but we need to know or at least be very conscientious about supplementing them with prebiotics, probiotics, and really supporting gut health otherwise.

Chris: Definitely. You know from a Chinese medicine perspective, you wouldn’t use herbs like berberine for just indefinitely over a long period of time. They’re more in the category of therapeutic use, but they can still be useful in that way. Sometimes getting the blood sugar into a normal range while the patient’s making those other adjustments to diet and lifestyle, and then once they’ve made those adjustments successfully, you can withdraw the berberine or whatever it is, and they can still stay there. That’s kind of that root–branch thing that we’re talking about. What about pharmaceuticals? Any that you think play a role here in some cases?

Amy: Yes. Metformin is a prescription medication that improves insulin sensitivity, and it’s most commonly used in diabetic patients. But it’s also pretty commonly prescribed to women with PCOS to improve the insulin sensitivity. I think this is actually a pretty effective medication, and some women tolerate it really well and it will do the job of improving insulin sensitivity. I’ll occasionally use metformin with some of my patients. The caution I have around this one is number one, it will deplete vitamin B12, so I’m going to make sure anyone on metformin should be supplementing with active forms of B12, so methylcobalamin, hydroxocobalamin. And the other thing is, metformin is associated with most common gastrointestinal side effects, so I’ll sometimes see nausea, gastrointestinal discomfort, abdominal pain, or bloating. It doesn’t always work for patients, and you and I also have the practice where a lot of patients come say, “No, I don’t want to use prescription medication.” I would say most of my patients don’t want to take metformin, but I think it is a pretty good option, especially when we’re starting to get around that pre-diabetic level.

Chris: Yes. I mean, some drugs are better than others, and some drugs actually do seem to have more of a relationship with the core mechanisms, actually addressing some of the root mechanisms that we’ve talked about. Low-dose naltrexone in that context, and metformin is an interesting medication. It’s shown to have a lot of interesting effects on insulin sensitivity and glucose tolerance. It’s being studied right now for cancer. We’ve talked a little bit about the metabolic theory of cancer in my podcast, and I think the jury is still out and there’s some controversy there. But there are some studies that suggest that metformin may slow the growth of certain cancers because it limits the availability of glucose to those cancers. So definitely interesting and may be worth consideration if all else fails. The difference is, you are going to do, in most cases, everything else before you go there, whereas the conventional approach might be the first step rather than exploring all these things.

Amy: Yes. I think in a conventional setting, you’ll probably get a prescription for all contraceptive pills and metformin.

Chris: Yes. That’s the basic standard practice there. Amy, I know your practice has been mostly full for the past year, actually for a couple of years, it’s been pretty full not shortly after you started, and the good news is, lately, we have made some changes to CCFM where we have brought in a nurse practitioner, Tracey, who is fantastic, and also a health coach, Danielle, who is also fantastic, and that has expanded our capacity and our ability to serve more patients because we have an additional layer of support now where patients can have appointments with either Tracey or Danielle in between appointments with us, and they just were able to get their questions answered even more promptly and just have that added layer of support. Now given that, you have a few openings in your practice again, which is fantastic, and tell us what kind of patients you’re working with these days and where your interests are and how that’s evolved for you over these last three years.

Amy: Yes. I feel like our practice does tend to draw sort of the more complex patients, and so I don’t know that I have a typical patient per se. We do get a lot of patients who come having been sick for quite a while, maybe having seen 15 or 20 other physicians and being told that’s all in their head, which is always heartbreaking when you hear that story. I generally do a general Functional Medicine approach and work a lot with gastrointestinal issues, autoimmune diseases, allergies, do a lot with hormones, also bioidentical hormone replacement therapy, when appropriate. More recently I’ve gotten into working with cognitive decline or mild cognitive impairment along the Bredesen protocol, heavy metal detoxification or a more general detoxification, and working with mold-related illness. These are all things that I have been focusing on the past couple of years.

Chris: And something that’s been really great too, as we’ve seen CCFM grow, we now have five clinicians—Dr. Schweig and myself as the co-directors, and then you, and then the latest additions have been Dr. Ramzi Asfour who is an infectious disease doctor who worked for the WHO for many years and living in different places around the world treating infectious disease. It’s been so incredible to have him on staff and to be able to learn from him and his deep experience with infectious disease. And then Tracey Clow or Tracey O’Shea, I should say, she just got married, she’s a nurse practitioner that’s IFM certified and has worked in pain clinics and is a phenomenal practitioner and resource. What I’m particularly enjoying is that we get to talk, share, communicate, and learn from each other all day. We have this kind of multiplier effect where if someone comes to see one of us, they’re actually in some way getting the shared experience of five different clinicians.

Amy: Yes. It’s been great getting everyone’s input, and in particular, because, I mean, you and I will often get to … as we talk about Functional Medicine, peeling the layers of the onion, we’ll end up burning into a chronic viral infection, tick-borne illness and Lyme disease is its own specialty, and it’s great having Dr. Schweig and Dr. Asfour to help manage these really complex cases.

Chris: Absolutely. I think we’ve developed a really interesting format where we have this collaborative model where we’re all sharing and learning from each other, and when you have a question, you come to me or Dr. Schweig, and when we have a question we all help each other out. We all have different backgrounds. It’s been amazing to have your radiology expertise because that often comes up. Patients will bring in scans and they will have questions about what the right diagnostic approach is for that, and we can ask you, and when it’s more on the infectious disease spectrum, Dr. Schweig and Dr. Asfour. In the nutritional realm of lipids and all of the things that I have gone down rabbit holes for, I’m happy, always happy to share. I think it’s a unique model that we have. I don’t see this at a lot of other clinics, and I’m really happy with how that’s continuing to unfold as we add additional practitioners and continue to grow.

All right. So, anything else, Amy, before we finish this up?

Amy: I think we covered it all.

Chris: Great. Well, it’s been great to have you on the show again, and for those folks who are looking for additional help and would like to work with Amy, Dr. Nett, you can head over to ccfmed.com, and then when you get there you can click on patients and then click on working with Chris and Amy Nett, and then you get all the information you need about how to apply to become a patient and where your path takes you. I wish you well and I hope that you continue to cultivate vibrant health and wellness.

Amy: All right. Thanks so much for having me on the podcast today, Chris.

Chris: It’s been a pleasure. All right. So, I know we’ve been doing a couple of interviews recently, but continue to send in your questions at chriskresser.com/podcastquestion. I will be returning to the Q&A format shortly. I like to mix it up, it keeps it interesting. Again, take care, everybody, and we’ll talk to you next time.

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Join the conversation

  1. NaPro technologies has, for many women, been the cutting-edge of natural fertility technology. I would really love to see a cooperation of information and learning between NaPro and Chris Kresser or Amy. There is too much that is being overlooked by both parties, in which I believe you both would greatly benefit. I wish more NaPro OBGYNs assigned dietary advice. Some are starting to, like Dr. Chris Stroud of Ft. Wayne, Indiana, and Dr. Michael Parker of Columbus, OH, but NaPro doctors need to be hearing this information as well. I would like you to please reach out to one of these doctors.

  2. Hi. I’ve been diagnosed with PCOS since I was a teen. I suffer from ALL the symptoms except acne. I’ve tried almost all the supplements and diet you’ve suggested in this podcast but never heard of berberine. I see it is sold in capsule forms. How much would you recommend to take per day? I am also pre-diabetic and decided not to go back on metformin as I can no longer tolerate it.

  3. I second NAC, and also CoQ10! Half my patients have PCOS, most undiagnosed when they come in, even after seeing OB/GYNs. In countries outside the U.S., AMH is also used as a diagnostic criterion. We see more “atypical” cases (no obesity or hirsutism) than typical these days. I’ve never seen a case of low DHEA with PCOS to date. I too would like to see the evidence of NAC lowering DHEA, as I have not heard this.

    • Hi Laura, where do you practice? Are you aware of any practitioners experienced with PCOS in the Chicago area?

  4. Zinc levels of 90-100 are suggested to be optimal for women in this podcast. What unit of measurement does this refer to? And as measured in plasma or serum? I assume plasma, since Chris Masterjohn suggests plasma as the better of the two as a marker for nutritional status in a podcast of his own that I recently listened to.
    I have long suspected zinc deficiency in myself, but am unsure of how to approach the situation, particularly as it relates to copper. It took me a couple of weeks or so to realize that 15mg of zinc citrate caused me debilitating insomnia, and my (very unprofessional) theory is that perhaps it somehow stirred up copper and caused this overstimulation.
    I have a very tricky case of PCOS that not one of at least 8 doctors in the past three years has been able to help me with. I suspect that replenishing a potential zinc deficiency could help me in many ways, but I’m not sure where to start.

  5. Hi. I’ve been diagnosed with PCOS since I was a teen. I suffer from ALL the symptoms except acne. I’ve tried almost all the supplements and diet you’ve suggested in this podcast but never heard of berberine. I see it is sold in capsule forms. How much would you recommend to take per day? I am also pre-diabetic and decided not to go back on metformin as I can no longer tolerate it.


  6. What would the Functional Medicine approach be to mild forms of Nonclassical Congenital Adrenal Hyperplasia (NCAH)? This can look very similar to PCOS and is often misdiagnosed as PCOS. Conventional approaches involve glucocorticoid therapy. The most reasonable conventional approach appears to be ultralow-dose dexamethasone, which often results in the reversal of infertility without suppressing endogenous cortisol production. Are there drugless options for this condition? Berberine, ashwagandha, phosphatidylserine, etc., would seem to be helpful in reducing androgens and dampening ACTH activity. Are there any other functional medicine considerations for NCAH that distinct from those of PCOS?

  7. Amy and Chris — I just wanted to say THANK YOU. You probably don’t hear it enough, but please know that I’ve benefited tremendously from your information and recommendations. As one of Amy’s patients, I appreciate everything you both do.

    I’m also enjoying your latest emails, Chris. And awesome work with the new book.

  8. NAC should be added to the list here. It increases glutathione. Scavenges free radicals itself also. Reduces glutamate hyperexcitability in the brain neurons helping anxiety. And it considerably raises SHBG and reduces DHEAS. Like almost in half for DHEAS. They induce ovarian dysfunction in lab animals by injecting high levels of DHEA.

    • Thanks @maddy, this was news to me about NAC. Surprisingly, a lot of fertility websites recommend Royal Jelly that raises DHEA levels. I assume Royal Jelly is a big fat no no as well? If PCOS is suspected? Or is it ok/required for some as long as zinc is supplemented as well?

      Cortisol does steal pregnelone so, DHEA may be required by some no?

    • Great comment. There is certainly more and more research coming out on NAC for a wide range of conditions, including PCOS and infertility. However, I have not seen anything about NAC specifically reducing DHEA by such a dramatic amount. I would love it if you could share a reference for the NAC/DHEA research, Maddy. Thank you in advance!