Could Copper-Zinc Imbalance Be Making You Sick?

Note: My process for testing zinc and copper levels has evolved. I no longer use the SpectraCell test mentioned in this podcast, and instead use serum or plasma zinc and copper to assess zinc and copper levels. I also sometimes use the Genova ION profile to get a more comprehensive view of micronutrient status.

In this episode of Revolution Health Radio, we cover:

3:07 Can someone without a gallbladder eat a Paleo Diet?
6:39 How to tell if you should avoid coffee, green tea, and caffeine
13:52 If you have this Copper-Zinc imbalance your body could be starving for oxygen…
21:52 Get these tests done if you have nervousness, anxiety, or mood swings
27:43 What to do – and not do – if your copper levels are high
33:46 Is 5-HTP safer than SSRI’s for anxiety and depression?
42:54 Why anti-depressants could permanently alter your brain chemistry… in a bad way
45:37 The surprising cause of depression (and no, it’s not low serotonin)
48:40 Are chocolate cravings related to magnesium deficiency?
53:22 How to get your Vitamin A and D ratio within healthy ranges

Links We Discuss:

• The Depression Series
• Light Therapy Machine for Depression
• Chris Masterjohn’s Vitamin A Article
• Recipes for liver (at the bottom)

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Full Text Transcript:

Steve Wright:  Hi everyone, and welcome to the Revolution Health Radio Show.  I’m Steve Wright from SCDlifestyle.com, and with me is Chris Kresser, health detective and creator of ChrisKresser.com.  How are you doing today, Chris?

Chris Kresser:  I’m pretty good, Steve.  How are you?

Steve Wright:  I’m doing well, as well.  I’m recovering from a chest cold over the holidays that I had, but today has probably been my best day so far, so I’m hoping it’s behind me.

Chris Kresser:  Glad to hear it.  Did you have a good holiday season other than that?

Steve Wright:  Yeah, it was great.  Lots of family time, lots of relaxing, and other than the stress of trying to hit a party every other day, it was great.

Chris Kresser:  Wow.  I kinda remember that, vaguely.

Steve Wright:  How was Canada?

Chris Kresser:  Dark and cold.  No, it was actually not that cold compared to last time; I think I mentioned it was 40 below when we went to visit Elanne’s parents, but this time it was a balmy 25 or 30 degrees, which was not that bad.

Steve Wright:  You could almost wear shorts!

Chris Kresser:  Yeah, right.  It’s interesting because I’m such a daylight person myself.  I’m not a night person.  I’m a day person.  I love being outside during the day and being really active, and up there at this time of year, it doesn’t really even get light until, you know, 8:30 or 9 in the morning, and then it’s already getting dark at 4, so the days are really short, and the good part of that is I ended up resting a lot, you know, and just really doing a lot of nothing, which is not my usual MO, and so it’s nice to have a little bit of time like that.

Steve Wright:  Yeah, that’s good.  Sort of a forced outage.

Chris Kresser:  Um-hum, exactly.  And from a sort of Paleo lifestyle perspective, that’s what the winter is supposed to be like, you know?  I mean our ancestors had a natural rhythm and flow throughout the year.  Certainly the spring and the summer were more active times, and the fall, late fall, and winter were times of contemplation and rest, and a lot of us aren’t really in tune with those natural rhythms anymore because of electric light and, you know, there’s often nothing that’s really that different about our lives in the winter and the summer in terms of our work schedule or something else that we’re doing, so it’s always nice for me to get back in touch with those natural rhythms.

Steve Wright:  Yeah, and the added sleep, I think, is a big bonus for me.

Chris Kresser:  Definitely.  Cool.  Well, we have some interesting questions.  Let’s dive in.

Can someone without a gallbladder eat a Paleo Diet?

Steve Wright:  Yeah, thanks everyone for sending in your questions, and let’s start with Angela’s first.  She’s curious how someone without a gallbladder does Paleo.

Chris Kresser:  Well, the common bile duct, which still remains after the gallbladder is removed, actually assumes a lot of the function of the gallbladder once it’s taken out, and that’s why it’s possible to take out the gallbladder and not have somebody just completely fall apart and be unable to digest any fat at all.  So, a lot of people do really well on Paleo without a gallbladder.  Some people may need to moderate their fat intake to some degree, although a lot of people don’t.  The type of fat seems to matter.  Coconut oil is a very good fat for people without a gallbladder because it doesn’t require bile acids for absorption, so it’s rapidly absorbed in the upper part of the small intestine, and it’s transported directly to the liver via the portal vein.  These are medium-chain triglycerides that I’m talking about, and in fact, they’re used in hospital tube-feeding formulas, you know, for people who have had surgery on their intestine or have had parts of their intestine removed because they’re so easy to digest and absorb.  So, coconut oil is definitely your friend if you’re lacking a gallbladder.  Then there are some other things that can be done to improve that function of the bile duct and help emulsify and break down fats.  Dandelion is a very commonly used herb in the Western pharmacopoeia.  It’s bitter and it’s a cholagogue, which means it helps with bile synthesis.  Ox bile can be used if you’re having trouble digesting fats.  You know, that won’t address the underlying cause of the problem, but it will help symptomatically.  It’s a similar approach to using hydrochloric acid when you have low stomach acid, but you’re actually using bile itself in this case.  So, that can be useful for people who don’t have a gallbladder or for anybody who is having trouble digesting fat, because that’s often one of the biggest difficulties that I see when somebody moves from a lower-fat diet to a higher-fat Paleo Diet is if they haven’t been in the habit of eating fat and producing bile that you need to break it down, they can often experience some difficulty with the high fat content, and so ox bile or dandelion root or ginger can all be helpful in breaking down the fat.

Steve Wright:  Well, what about lipase?  Would someone want to take an enzyme like lipase for this?

Chris Kresser:  Sure, that can work too.  You know, we talked before about how I generally prefer HCl to correct the problem at the top, and if the food in the stomach is properly acidified, then the pancreas should secrete all of the necessary enzymes, but the NOW Super Enzymes are a good choice at least temporarily while you’re resolving the underlying issues.  That can be helpful too.

How to tell if you should avoid coffee, green tea, and caffeine

Steve Wright:  All right, great.  Let’s move on to question #2 from Jeff, and it is, “What is your take on coffee, green tea, and caffeine consumption in general?  Robb Wolf and his cohort seem fine with it, but Mat ‘The Kraken’ Lalonde is against it.”

Chris Kresser:  Well, everyone is probably tired of hearing me say, “It depends,” for questions like this, but I’m gonna have to say it again because I do think it depends.  Caffeine is subject to individual tolerance, just like dairy products and starches, white rice, things like that.  Certainly I don’t think that anyone benefits from drinking, you know, three to five-plus cups of coffee a day and drinking three or four Red Bulls.  That’s not gonna help anybody out, but a single cup of coffee, for example, or a couple of cups of green tea, at least according to the scientific literature, may have health benefit, but it really depends on how somebody responds and what their current circumstances are.  So, let’s just use a couple examples.  Let’s say somebody sleeps well, their energy levels are fine, they don’t have any problems with blood sugar regulation, no adrenal fatigue issues, they’re generally healthy, and they have a cup of coffee each morning.  Is that a problem?  I don’t think so.  I mean there’s no research that shows that that’s a problem really, and if they’re not suffering from it, then I don’t think it’s an issue.  On the other hand, take somebody who is sleeping very poorly, they crash in the afternoon, they have wild blood sugar fluctuations, they feel jittery and agitated, they crave sugar, they’re dealing with depression or anxiety or mood swings, or any number of psychological issues like that.  That person, even one cup of coffee could be a big problem.  It could really prevent them from getting the rest that they need to heal, prevent their adrenals from recovering; and in some cases, even green tea would be too stimulating for them, but they should be able to determine that by going completely caffeine-free for a period of time.  If I was their healthcare practitioner, that’s what I would recommend if we were doing an adrenal protocol.  We’d take them off caffeine completely, with the possible exception of something like kukicha, or twig tea, which is made from the branch of the green tea plant instead of the leaf, and it’s really, really, really low in caffeine.  It provides just a mind-clarifying kind of effect, but it’s rarely stimulating enough to make a difference, so I might allow that.  But if we take them completely off caffeine for a period of time and then they add it back in, they often find that when they get that kind of space from it, it becomes pretty obvious that it’s too much for them to tolerate.  So, it’s really an individual issue.  There are other circumstances to be considered.  Like green tea has shown some benefit, and caffeine in general has shown some benefits, for weight loss, but I’m hesitant to recommend it for weight loss because, in my experience, a lot of people are having difficulty with weight partly because of adrenal issues.  You know, their cortisol is too high or too low or it’s fluctuating inappropriately, and if those people do a caffeine stack for weight loss, it could actually worsen some of those underlying mechanisms.

Steve Wright:  OK, so what about the middle road?  What about the average Paleo person who is on the diet?  They’re doing their best to get some sleep, but they really love, you know, one to three cups of coffee in the morning.  Are they going to be all right on that, or should they take some time off and see what happens?

Chris Kresser:  Yeah, I think everybody benefits from taking some time off and seeing what happens, and that’s true with any other gray-area foods, and I talk about this in the PersonalPaleoCode.  You know, there are a number of foods that are just pretty much safe for most people, and those are what are included in the 30-day Reset, but then there are a bunch of foods that are gray area, which means that they are really subject to individual tolerance.  So, that could be dairy products, it could be starches and then white rice or soured buckwheat, could be caffeine, chocolate, nightshades, eggs, FODMAPs, a lot of the stuff we’ve talked about on the show, and I think nearly everybody would benefit from taking a period of time and going without caffeine.  Now, that can be difficult, of course, as anybody knows who is drinking a lot of caffeine and tries to stop, and I actually don’t recommend that you do it cold turkey because that can be problematic.  You would titrate off of it slowly to make it not as dramatic and difficult.  I don’t think someone who is dealing with potential adrenal issues should be drinking three cups of coffee a day.  One cup, you know, that’s arguable, and maybe if you stop it for a period of time and you add it back in and you really don’t notice that much of a difference, you can make an argument for continuing, but I think most people who are struggling with anything that could be construed as adrenal fatigue should stay away from coffee and should maybe stick with lower-caffeine green teas, green tea that is only steeped for a short period of time so it’s not as strong in caffeine as, you know, a green tea that was steeped for a longer period of time.  Or, if you’re gonna do coffee, maybe doing half decaf and half caffeinated or something like that.

Steve Wright:  OK.  Another thing I want to throw in there is Tim Ferriss, in his book The 4-Hour Body, likes to recommend taking green tea extract that has been decaffeinated, so if someone is looking to stack something for weight loss, that might be a potential avenue to look at.

Chris Kresser:  Um-hum.  Yeah, definitely, although part of the benefit theoretically is the caffeine for weight loss, but I think you’re right.  You get the benefit without the potential downside just by doing the green tea extract.  And there are a lot of other benefits with green tea extract, as well, beyond weight loss in terms of reducing oxidative damage and some other neat stuff.

Steve Wright:  All right, so green tea over coffee, and keep it before noon.

Chris Kresser:  Sounds good.

If you have this Copper-Zinc imbalance, your body could be starving for oxygen…

Steve Wright:  Let’s roll on.  This question is from Allison.  She would love to hear your thoughts about the copper-zinc balance and whether you’ve heard of pyroluria.  What sort of presentations do you see?

Chris Kresser:  Pyroluria.  I wish they would rename that.

Steve Wright:  Me too.

Chris Kresser:  It always sounds funny to say it.  So, let’s talk about this first because I think a lot of people haven’t heard of it, so I need to give a little background about the condition, and then we’ll come back to the copper-zinc ratio and how that relates to pyroluria.  And then we’ll talk about more specifics about copper-zinc imbalance and what to do about it if you’re suffering from it, and how to identify it in the first place.  So, pyroluria is a genetically determined chemical imbalance that involves a defect in hemoglobin synthesis, and hemoglobin is the protein, as I’m sure some of you know, that holds iron in the red blood cell and is responsible for delivering oxygen to the tissues.  So, every cell and tissue in the body needs oxygen and glucose to function properly, and if you’re not getting oxygen to the tissues, as is the case with anemia, nothing is gonna work right.  None of your cells are going to work right.  It’s one of the first things that I look at when I do a case review and I run a comprehensive blood panel on my patients is oxygen deliverability and blood sugar regulation because those two are what I call deal-breaker issues, meaning if they’re are out of whack, nothing else that we do is gonna be very effective until we get those two systems working properly, so it’s really important and this is why pyroluria can be a really challenging condition to experience and to work with.

Steve Wright:  Would I know that I had that from birth, or would I have to get some sort of genetic test?

Chris Kresser:  Well, you have to get a test.  I can’t remember the name.  I think it’s the mauve something or rather.  So, people who have this condition produce too much of a byproduct of hemoglobin synthesis called kryptopyrrole, and kryptopyrrole has no known function in the body, and it is largely excreted in the urine, so the test that you get tests for the levels of kryptopyrrole, and if it’s too high, then that’s a sign that you have pyroluria.  So, kryptopyrrole binds to vitamin B6 and zinc and makes them unavailable as co-factors in the enzymatic and metabolic processes that they participate in.  And then excess kryptopyrrole also leads to a deficiency of arachidonic acid, or AA, which is an important fatty acid in the tissues.  So, a lot of people with pyroluria will exhibit mild to moderate signs of B6 to zinc deficiency, and so that’s usually what happens.  You know, they go to the doctor and they might be experiencing poor stress control, nervousness, anxiety, mood swings, just a lot of psychological symptoms like feeling really tense, or episodic anger is one of the kind of classic signs, like explosive temper, poor short-term memory, and depression because they can’t create serotonin well.  Serotonin, of course, is a neurotransmitter that reduces anxiety and depression, and vitamin B6 is a rate-limiting factor; it’s an important factor in that last step of the synthesis of serotonin.  So, if you don’t have vitamin B6, you can’t make serotonin properly, and people who have pyroluria don’t have enough B6 usually.  So, let’s get back to the copper-zinc ratio and show how this relates to pyroluria.  So, the body has a pretty elaborate system for managing and regulating the amount of trace minerals like zinc, copper, iron, manganese, and chromium in the blood, and what happens is if blood levels of any of these trace minerals are depleted, then we have a system for absorbing them from the diet, and then they are transported from the blood into cells if the cellular levels are inadequate, or they’re excreted from the body if blood and cell levels are sufficient or overloaded.  That’s the way the system is supposed to work, but in various cases of either genetic diseases or diseases that have environmental causes, that system breaks down, so you get people either absorbing too much of a particular trace mineral more than they need, like with hemochromatosis, which we’ve talked about, or you get people that have deficiency of some of these key minerals, like zinc deficiency with pyroluria.  One of the most common and important imbalances that we see in clinical practice with trace minerals is excess copper and deficient zinc.  So, the ideal ratio between these two, if copper is in the numerator and zinc is in the denominator, would be 0.7 to 1, which means anywhere from 70% as much copper as zinc to even amounts of each.  And one of the ways that you can recognize this or when you might suspect this, and this will tie into a future question that we’re gonna talk about a little bit later in the show, is that copper and zinc are not only minerals, but they’re also regarded as neurotransmitters in the brain.  They have some of the functions of a neurotransmitter, so an imbalance in copper and zinc will lead to things like hyperactivity, ADHD, other kinds of behavioral disorders, and depression; and in fact, a lot of people who are labeled with autism and even paranoid schizophrenia, when they test their copper levels, they find out that they’re elevated.  Then high copper can cause severe PMS.  That’s another red flag for me where I’ll consider it.  It can cause estrogen intolerance, and it can cause skin issues, so people with excess copper have a high incidence of acne or eczema, psoriasis, just sensitive skin in general, sunburn, people who are really apt to get sunburned even if they’re only out for a short period of time, headaches, poor immune function.  Another characteristic sign is white spots under the fingernails, excess copper and deficient zinc, that can happen.  And then elevated copper is a special problem for people with low blood histamine levels and overmethylators, and that can lead to anxiety and even panic disorders and paranoia and, in severe cases, hallucinations.  So, as you can see, most of the effects are nervous system related, nervous and endocrine system, I would say, with particular impact on the brain and behavioral health.  So, those are the things to look for when you’re considering copper-zinc imbalance as a potential issue.

Get these tests done if you have nervousness, anxiety, or mood swings

Steve Wright:  It seems pretty serious, so how would I go about testing for it?

Chris Kresser:  Oh, yeah, it’s definitely serious.  I mean, there’s a syndrome called Wilson’s syndrome that’s a severe excess copper problem.  Actually you’ll see low copper in the blood, but you’ll see very high copper with a 24-hour urine test, and that can cause severe brain damage and difficulties.  I have a friend who had Wilson’s syndrome, and when she first figured out, or when people around her first figured out what was going on, she had lost the ability to speak, and when she gained the ability to speak again, her voice was very slow and deliberate, and it was difficult to understand her, and she’s made a lot of progress and is feeling a lot better and is getting back to normal, but it was a pretty scary thing, and she ended up at the Mayo Clinic.  So, yeah, this is definitely something to pay attention to.

Steve Wright:  Yeah, I’m glad she’s getting better.  You called it Wilson’s disease.  Is that something that can onset in anyone?

Chris Kresser:  Well, there’s a strong genetic predisposition for that, but we don’t fully understand, you know, what all the factors are.  In her case, there was probably a genetic predisposition plus an excess of copper in the diet or copper from other sources, which we’re gonna talk about here in a second.  But Wilson’s is different than just standard copper-zinc imbalance.  They’re not the same thing.  They don’t present in the same way, so I’m not suggesting that copper-zinc imbalance will lead to Wilson’s.  I was just pointing out, using Wilson’s as a way of explaining how serious excess copper can be.  These metals, the trace minerals are potentially lethal.  It’s the same with hemochromatosis, as we talked about before.  That can cause really, really serious problems, including death eventually, so not harmless, for sure.  So, testing for copper and zinc, I use blood tests, just serum testing of copper and zinc.  There is hair mineral analysis, urine testing, other forms of testing.  You know, to be honest, the jury, for me, is still out with hair mineral analysis.  I’ve seen some studies suggesting that it might be accurate in the case of certain nutrients especially, and then I’ve seen a lot of other research indicating that it’s not reliable.  If you look in the mainstream scientific literature, you know, it’s mostly dismissed as not being reliable.  If you search on the Internet, you’ll find lots of kind of random websites saying that it is, but being a little bit of a skeptic myself, I’m not yet convinced that it’s reliable, so I do serum copper and zinc testing and use the ratio above that I just mentioned of 0.7 to 1.

Steve Wright:  I’ve read a lot, or I’ve heard a lot, that zinc serum tests don’t represent the correct number and that you should do, like, a Zinc Tally taste test.

Chris Kresser:  Yeah, I’m not convinced about that either.  I mean if someone has some good, peer-reviewed, placebo-controlled research, if you do, Steve, send it to me.  I’d like to take a look at it, but most of that sort of stuff that I’ve read has been not in the peer-reviewed literature.  It’s just been on, you know, random websites and stuff, so I’m still waiting to see that evidence.

Steve Wright:  OK.

Chris Kresser:  Have you seen it?

Steve Wright:  It’s been a while since I’ve looked into this issue, but I swear it was like one doctor, and my guess is he didn’t publish in a peer-reviewed journal, but he published his own study about it.  So, I’ll try to dig it up and send it to you, but I do know from my own experience that I tried the Zinc Tally taste test, and Thorne Research makes one that you can buy, and I bought the solution, and I put myself through it and I didn’t taste anything.  And then I put several of my family members and friends through it just to see what would happen, and I would say 60% of them right away would, like, spit it out and say, “Ugh, this is gross.”  However, when I put it in my mouth, I was like, “Eh, this tastes like water,” and I supplemented with a lot of zinc over a period of six weeks or eight weeks, and I gradually got that flavor back to the point where it tasted pretty awful.  So, you know, that doesn’t make it right or wrong as far as tests go, but that’s my experience.

Chris Kresser:  Yeah, well, I’ve had patients who have used the Tally, a couple, and one who had no problem with it and the other who absolutely couldn’t handle it at all; it was just revolting immediately, and she was zinc deficient and he wasn’t, according to the blood tests.  So, there was a concordance there, but I’d be curious to see more evidence of how they correlate, those two ways of testing.

What to do — and not do — if your copper levels are high

Chris Kresser:  In any event, people who are eating–well, let me back up.  We’ll talk first about the main sources of copper because if you have excess copper, you’re gonna want to reduce your intake of copper from food, and you’re gonna want to reduce your exposure to copper in the environment.  So, copper is mostly found in vegetarian or plant proteins like nuts and beans and seeds and grains, and meats do contain copper, but they’re balanced by zinc, which competes for the absorption of copper, so a Paleo, Weston A. Price type of diet that’s high in animal protein, it’s unlikely you would develop a copper-zinc ratio just from eating that way because the zinc competes with absorption for copper in those foods.  Chocolate is high in copper, and actually, in some cases, when people are really craving chocolate, you often hear that they’re craving magnesium, and that may be the case, but they may also be craving copper.  Drinking water that is in copper pipes can have copper in it, so if you test high in copper and you’re living in a house with copper pipes, that may be something you want to look into.  There’s copper cookware, which I don’t recommend using.  Some dental materials have copper in them.  Certain vitamins have copper.  If you like multi’s, you want to check and make sure your multi doesn’t have it if you have excess copper.  Fungicides and pesticides have copper residue, and then IUDs and birth control pills have copper, as well.  So, those are the primary sources of copper in the environment and food, and then there are some things that deplete zinc levels, like stress, for example.  Any disturbance of homeostasis or oxidative stress will deplete zinc levels over time.  So, it’s important to manage your stress if you’re dealing with copper imbalance.  One of the first things I would do with patients like this is order a SpectraCell micronutrient analysis, which tests micronutrient levels within the white blood cell, and that can help determine if there are deficiencies of other micronutrients that help reduce copper buildup.  So, these are things like vitamin B1, B3, B6, folate, inositol, and choline, and those are all antagonistic to copper, and then there are some minerals that are antagonistic to copper, like zinc, of course, which we’ve been talking about, manganese, iron, sulfur, and molybdenum.  You want to be careful with the iron, though, of course, because if you are iron-loaded, you have too much iron, and you take iron to reduce copper, that may help solve one problem and cause another, or exacerbate another.  And then there are some studies I’ve seen that suggest that copper might be excreted by binding with glutathione, so yet another reason to maintain healthy glutathione levels; and glutathione levels are often depleted in cases of chronic illness and stress, so that’s another thing to pay attention to.  Then you want to improve the detox function of the liver and the skin.  You can do things like sweats and saunas.  And then, of course, you want to do a diet that is based on animal proteins and lower in the plant proteins that tend to be rich in copper, like the nuts and beans and seeds and grains, like I mentioned earlier.  So, those are the basic steps.

Steve Wright:  To summarize those, it’s basically look for any environmental triggers that are adding a lot of copper to your diet, cut out the high-copper foods, and then look to possibly supplement with any other micronutrient imbalances you might have?

Chris Kresser:  Exactly.  And on top of that, improving glutathione levels, improving the detox function of the liver, and improving adrenal function, and managing any form of stress, whether it’s dealing with inflammation or oxidative damage or psychological stress and adrenal stress.

Steve Wright:  OK, so let’s say that I find out that I have high copper and low zinc.  Do I start supplementing with zinc right away?

Chris Kresser:  It’s probably best to get some help from someone who has some experience dealing with this, because it can get a little bit complex, depending on the status of other micronutrients, and you know, I mentioned Wilson’s disease before.  That wouldn’t present with high serum copper.  It usually presents with low serum copper, so they’re not often confused that way, but depending on how you tested for elevated copper, it may be something that you want to rule out, Wilson’s.  But, in general, just following the steps that I outlined for a lot of people should be sufficient.  Zinc is definitely one of the things you would supplement with, especially if the zinc is deficient.  So, it’s important not just to test copper.  You would test copper and zinc at the same time, and if zinc is low, then you definitely would want to bring it back up.

Steve Wright:  OK, so to wrap it up, it’s something you should definitely get tested if you’re exhibiting any of the problems that Chris was mentioning, and I think we’re gonna move on to the next question, unless you have anything, Chris?

Chris Kresser:  No, I think that’s it.

Steve Wright:  OK, copper and zinc.  Got it done.

Is 5-HTP safer than SSRIs for anxiety and depression?

Steve Wright:  All right, this one’s from Breaking All Illusions.  “What do you think about the use of 5-HTP as a natural supplement for anxiety and depression?  Do you consider it safer or more effective than SSRIs?  And do you consider it safe/effective at all?  If so, how would you recommend using it?”

Chris Kresser:  OK, so 5-HTP is an intermediate in the conversion of tryptophan to serotonin, so tryptophan gets converted to 5-HTP, and then 5-HTP gets converted to serotonin.  As I’m sure many people know, some people who are depressed have issues with serotonin synthesis or metabolism, and that can cause depression, and in those cases, 5-HTP might be helpful.  There is some research that’s fairly promising, but I think the jury is still out on it.  But as I pointed out, I wrote an entire series on depression, ChrisKresser.com/depression.  Hopefully that will be updated soon because there’s a lot that I’ve learned since I wrote that.  It’s all still completely valid, but I want to add some information about the inflammatory cytokine model of depression, which I’m gonna talk about in a minute.  But in that series, I pointed out that not all depression is as simple as being a serotonin deficiency, and that is really just a convenient fiction that’s been manufactured by drug companies to sell more antidepressants.  Doctors in 2009 wrote 235 million prescriptions for antidepressants, which is just a mind-boggling number.  It’s a 14 billion dollar market for antidepressant drugs, so it’s a huge business, and the drug companies know that if they create a really simple model for depression, which is basically depression equals serotonin deficiency; therefore, if you take a drug that raises serotonin, that will cure and treat depression.  But the reality is a lot more complex than that, as anybody who works with depression knows or who has experienced it knows, and the drug trials on antidepressants, when you really look at them and you look at careful meta-analyses that have been performed by Kirsch and colleagues and others, you see that for mild to moderate depression and even fairly severe depression, antidepressants are often no more effective than placebo.  And a lot of the natural treatments, which we’re gonna talk about here in a second, are just as effective as antidepressants, with far fewer side effects.  So, 5-HTP may be one of those, but it doesn’t have the research behind it that some of these other natural therapies do.  So, if you’re gonna try 5-HTP, I would recommend starting with a pretty low dose, which would be maybe 20 mg in the morning, and it’s important to take it on an empty stomach.  And then you can continue to increase your dose every few days up to 100 mg, and I wouldn’t go above 100 mg.  Some people out there, some of the studies recommend 200 or 300 mg, but I don’t recommend that for a number of reasons.  So, somewhere between 20 and 100 mg.  If you take it before bed, it can sometimes help with sleep, so that’s another possibility, but I’ve found with patients that it’s more effective for depression if you take it in the morning.  But that’s not the first thing I would try with depression, and in fact, these days I’m looking at it much more as an inflammatory condition, which again I’ll come back to in a moment.  I wanna talk a little bit about some of the natural treatments that have been proven to be effective.  Psychotherapy is, of course, one of them, and it’s often left out when we talk about natural treatments for depression because I think a lot of times we’re thinking of, you know, nutrients or herbs or pills or things that we can take, but psychotherapy, particularly cognitive behavioral therapy, which is a specific type of psychotherapy, has compared favorably with antidepressant drugs in a lot of trials, especially in the short term, even when the depression is severe, and over the long term, it actually appears to be superior to medications.  And then some studies have looked at medication plus psychotherapy versus just medication alone, and of course, that’s almost always more effective, so that’s something to certainly consider, and I would definitely recommend it as part of a protocol for depression in any case.

Steve Wright:  When you say medication, are you talking about SSRIs and SNRIs?

Chris Kresser:  I’m talking, yeah, about both, but primarily SSRIs.  They’re the bigger drug class by far still even though there has been more of a trend to SNRIs lately, but a lot of the research that has been done in the comparisons has been more with SSRIs.  Exercise is at least as effective as antidepressants in treating depression, according to the research literature, and the good news about exercise is the only side effects of exercise are usually other health benefits and reducing your risk for a number of other diseases.  Light therapy, and there was a study in 2005 in The American Journal of Psychiatry that found that it was just as effective as antidepressants.  One of the arguments about that study was that it could have been placebo, and that’s true, but if that’s the case, you know, who cares?  If there’s no negative impact other than spending the 75 bucks or whatever on the machine, actually maybe we can put that in the show notes.  There’s a machine that I recommend on Amazon; I think it’s about 75 bucks.  You know, the only thing you might lose is a little bit of time in the morning and a little bit of money to buy the machine, but there really aren’t any significant side effects associated with it.  St. John’s wort, which I’m sure a number of people have heard of, it’s probably the most popular treatment for depression in Europe.  It’s just as effective as antidepressants in clinical studies, but it has 10 times fewer side effects.  One important thing to keep in kind with St. John’s wort is that it takes several weeks often for the effect to come on fully, so it’s not something that you just start taking and you feel the benefit right away.  It takes about three to four weeks to really get the effect.  Another thing I’ll mention is not to mix these treatments together with drugs.  I mean, exercise and psychotherapy, of course, is fine, and even light therapy, but I would not recommend combining St. John’s wort with antidepressants without supervision.  That can be dangerous.  And the same with 5-HTP and any other nutrient-based or herbal-based remedy.  Acupuncture has been shown to be pretty effective for depression.  In fact, there was a Cochrane review, Cochrane being one of the prestigious group that does meta-analyses of available research on a particular subject.  They found, “There is no evidence that medication was better than acupuncture in reducing the severity of depression.”  And again, just like exercise, acupuncture has very few side effects except feeling better in other ways.  So, those are a number of options for someone who is dealing with depression and doesn’t want to take the drugs or eventually wants to get off the drugs.  Again, it’s really, really important if you are taking a medication for depression not to stop taking it abruptly and to do it under the supervision of someone who is experienced in getting people off SSRIs and other forms of antidepressants, because stopping them cold turkey can really wreak havoc with your brain chemistry, and the problems with suicide that are associated with antidepressants most often occur when people are just starting the medication or just coming off of it.  So, it’s not something to play around with, and it’s really important to find someone who has experience getting people off of those drugs, if you choose to come off of it.

Why antidepressants could permanently alter your brain chemistry… in a bad way

Steve Wright:  Is there also a long-term consequence of staying on the drugs for a number of years?

Chris Kresser:  I think there is, and I wrote about this in my series.  There’s a lot of pretty disturbing research that shows that SSRIs can cause permanent changes in brain chemistry, and it’s difficult to talk about this because, you know, a lot of people are on antidepressants, and some people are helped by them.  Even though the research is pretty equivocal, you have to consider that research is about averages.  You know, when you do a study and statistically at the end of the study there was no difference between placebo and the intervention, in this case an antidepressant, it doesn’t mean that there weren’t some people that benefited from the antidepressant in the study.  It just means that on average, when you take all the results together, there was no statistically significant difference between the two treatments.  I know people that have taken antidepressants and that have benefited from them, and of course, I know people that haven’t, so I’m not saying they never work.  I’m just saying that statistically speaking, from a research perspective, they are not better than other treatments, in general, except in the cases of very severe depression.  So, I’m not making any judgements of anyone who chooses to take antidepressants, and it’s a little bit scary to tell someone that a drug that they’re taking can cause permanent changes in brain chemistry, but I also feel it’s important to get the word out about this so that people think really carefully about going on these drugs before they choose to do so.  So, the research shows essentially that those changes that are made in the brain can basically predispose you to depression more for the rest of your life.  So, they create changes in the brain that make it more likely that you’ll need to be on an antidepressant or have some other kind of treatment for depression indefinitely, and that’s what scares me the most about these drugs, and unfortunately that is not, you know, very few patients are told that before they go on a drug.  I think very few doctors even know about that research, but I wrote about it pretty extensively in the Depression Series.  There are a lot of references there, and there are some great books that I linked to as well, where you can read all about that research if you’re interested in it.

The surprising cause of depression (and no, it’s not low serotonin)

Chris Kresser:  So, before we finish up with this question, I want to talk a little bit about a newer perspective on depression that we discussed in an earlier show.  We talked about it in the gut-brain axis program, and this is known as the inflammatory cytokine model of depression, and the theory essentially is that inflammation, which often originates from the gut, produces inflammatory cytokines, and these cytokines travel through the blood, they cross the blood-brain barrier, and then they suppress activity in the frontal cortex, and then that, of course, causes depression, the frontal cortex being responsible for some of the higher brain function.  So, one of the most important things you can do if you’re dealing with depression, if you haven’t already done this, is eat an anti-inflammatory diet and fix your gut.  Anti-inflammatory diet being a Paleo-ish diet, a Personal Paleo Code-ish type of diet, and then all of the steps that we have discussed lots of different times towards healing your gut, and I think that those are kind of the first steps that should be done when somebody is dealing with depression, and then if you eat that diet and you fix the gut and deal with any other potential sources of inflammation like a chronic infection; for example, a viral infection or a bacterial infection that may not be in the gut but outside of the gut.  So, if you deal with all of those sources of inflammation and you’re still experiencing depression, that’s when I would turn to some of these other natural remedies.

Steve Wright:  So, when you start fixing the gut, it’s not necessarily advisable to look towards trying to replace any neurotransmitter losses in the dopamine or serotonin areas?

Chris Kresser:  That’s kind of the last step, maybe.  You know, it’s like fix the gut, reduce inflammation, any other sources of inflammation, then consider some of these other natural treatments that we just talked about that would indirectly regulate brain chemistry:  psychotherapy, acupuncture, St. John’s wort, light therapy, exercise, possibly 5-HTP.  And then there are some products that I might use that improve serotonin or dopamine or acetylcholine or GABA synthesis and metabolism, but even then, they’re a milder, safer, and more natural approach than SSRIs or SNRIs.  I consider those drugs to be a last resort.

Are chocolate cravings related to magnesium deficiency?

Steve Wright:  All right.  Well, let’s roll on here.  You mentioned it earlier in the show, but chocolate cravings — both Martin and Evan were asking about magnesium, and so here’s Evan’s question:  “What are your thoughts about chocolate cravings being related to magnesium deficiency?  As a raw vegan, I didn’t touch chocolate for two years probably, and now I can’t get enough of it.  I’m way beyond your recommendation of a piece about the size of a silver dollar.  A full bar or more is reasonable,” and I think that’s on a daily basis, so he would like to know more about the topic of magnesium, chocolate, and magnesium oil applied topically.

Chris Kresser:  Yeah, OK, so one of the easiest ways to figure that out is just start doing some fairly high-dose magnesium glycinate or malate supplementation.  So, you know, take 600 mg a day for three or four weeks, and if the craving for chocolate disappears, then you could suspect that it had something to do with magnesium deficiency.  But if you’re still eating that full bar of chocolate every day after a month of that kind of magnesium supplementation, then I have a feeling that it has something more to do with something else in the chocolate, maybe the sugar or the caffeine or, you know, some other substance or combination of substances.  Perhaps copper.  I mean, we mentioned that earlier, although copper deficiency is fairly rare in people who are eating a — I just don’t see copper deficiency very often, but you can check for it.  Transdermal magnesium oil — it’s another one that I’m a little bit uncertain about, and when you look in the scientific literature, there are no studies other than studies that are done by companies that sell magnesium oil that show that it’s an effective way of delivering magnesium.  However, I have patients who have not experienced any benefit from taking even the chelated forms of magnesium, like glycinate and malate, but have experienced a fairly dramatic change after using transdermal magnesium oil.  So, I don’t see how it could do any harm, and if you try it and it helps improve your symptoms, then maybe it does work.  And, you know, lack of proof is not necessarily proof against, so it’s possible that we just don’t have the research on this yet.  I remember trying it a while back, and I didn’t really notice that much of a difference, but I don’t think that I was significantly magnesium deficient either, so I’m probably not the best test case.

Steve Wright:  Were you eating a bar of chocolate a day?

Chris Kresser:  No, I wasn’t.  You know, I’m irritating to some people in my discipline around those things.  It’s not even discipline.  I just don’t crave it.  I have sometimes a little piece that size after a meal, and that’s all I really need to satisfy the craving, so I’m no hero of discipline.  I just, for whatever reason, don’t have that kind of relationship with it.

Steve Wright:  It’s interesting.  So, with the magnesium supplementation, would you recommend that before bed?  Is there a certain time there?

Chris Kresser:  Yeah, two times a day usually, so in the morning and then in the evening.  If people are using it for constipation and they want to promote a healthy bowel movement in the morning, you could take two times the dose in the evening and maybe a smaller dose in the morning.  Or, you could even take it all in the evening, maybe with dinner as a good approach.  If you’re using it for muscle pain, muscle fatigue, and just general health, it doesn’t really matter as much when you take it.

Steve Wright:  OK, and with magnesium glycinate, just to remind everyone that there is gonna be an upper level for them at which they’ll start to cause loose stools probably, right?

Chris Kresser:  Yeah, it’s a higher upper level than with oxide or citrate, which is one of the reasons I recommend it, but one approach is dosing intolerance, just like you do with vitamin C.  So, you can keep increasing the dose until you hit the loose stools, and then you can go back a little bit, but I find that for most people, unless they’re severely magnesium deficient, a dose of somewhere between 400 and 600 mg a day will be sufficient.

Steve Wright:  OK.

How to get your Vitamin A and D ratio within healthy ranges

Chris Kresser:  So, I think we have time for one more short one.  How about the vitamin A-D ratio question?

Steve Wright:  Sure.  This comes from Michel, and he or she, I’m sorry, is asking about the ideal ratio between vitamin A and vitamin D.  Should one be higher than the other, and by how much?  They’re worried that vitamin D is being hyped so much that people are going to tend to consume too D and not enough A.

Chris Kresser:  Yeah, I think that’s a valid concern, and one of the reasons that I like the Weston A. Price Foundation approach is they put a lot of emphasis on the importance of fat-soluble vitamins, and that’s not something that’s really discussed in the Paleo world very often.  Fat-soluble vitamins — we’re talking about A, D, K2, and E — they play so many crucial roles in health, and they’re difficult to obtain from food in most cases, particularly K2 and A, you know, and D, if you’re not eating seafood.  But there has been a lot of hype about vitamin D, and then there’s been a lot of hype in the other direction about the danger of vitamin A, particularly for pregnant women or women who are trying to get pregnant; they’re really freaked out, unfortunately, about vitamin A because it’s a crucial nutrient for healthy development of the fetus, which I talk about in The Healthy Baby Code.  The important thing to understand about these fat-soluble vitamins is they exist in a synergistic relationship, and when you have problems with toxicity of one of them, it’s almost always contributed to by, or even only possible in the face of, a deficiency of one of the others.  So, for example, all of the problems with vitamin A toxicity that people are afraid of are only really possible in the presence of concurrent vitamin D deficiency, and Chris Masterjohn has done some great work on this.  I think there’s an article on the Weston A. Price website that he wrote called — I think if you search for vitamin A / osteoporosis in the search engine on their site, you’ll find it, but he talks about a study, and I mention this in The Health Baby Code, too, where when people are supplementing with vitamin D or they have adequate vitamin D levels, the toxicity threshold for vitamin A goes up to like 200,000 IU a day, which is an absurd amount of vitamin A.  Like to put that in perspective, 3 ounces of liver have about 27,000 IU of vitamin A, so you’d have to eat 30 ounces of liver every day to exceed the toxicity threshold, and I don’t know anybody who is eating 30 ounces of liver a day, so that’s just not going to happen.  And likewise, vitamin D toxicity will happen at a lower level if vitamin A and vitamin K2 are deficient, because vitamin A and K2 protect against vitamin D toxicity.  So, as I’ve said on the show before, I think an ideal range for vitamin D is somewhere between 35 ng/mL and maybe 60 or 65 ng/mL.  I don’t see any reason to go higher than that.  I don’t agree with, you know, some of the people pushing vitamin D levels above 100 ng/mL.  Studies show that you’re at risk for hypercalcemia because vitamin D regulates calcium metabolism, so you start to get issues with kidney stones and stiffer arteries, which, of course, increases the risk of cardiovascular disease.  Whereas, vitamin K2, which also has an effect on calcium metabolism, it makes sure that the calcium ends up in the bones and teeth and the hard tissues, and not in the soft tissues.  So, the key thing here is balance and making sure that you have enough of these fat-soluble vitamins.  Vitamin A is only really found in significant amounts in organ meats and cod liver oil.  It’s found to a lesser extent in grass-fed dairy, and that’s why I’m always talking about cod liver oil, especially for people who are on a strict Paleo diet and who aren’t eating grass-fed dairy or organ meats, like liver.  So, getting back to the question, which I’ve kind of gone off on a tangent from, there’s not a lot of research on the ideal ratio between vitamin A and vitamin D, but there was a recent paper by Dr. Holick that suggested that ratios between 4 and 8 times as much vitamin A as D would be ideal, and then the lead author on that paper, Dr. Linda Linday, had used cod liver oil with a ratio in that range to successfully protect against upper respiratory infections, and then there was some other research showing that that range of ratios is ideal in chickens.  I don’t know how applicable that is to humans, but if you look at the amount of vitamin A and D in foods like cod liver oil, then it’s a roughly similar ratio, and that’s, I think, a good ratio to shoot for, and if you eat liver, 2 to 3 ounces of liver once or twice a week, or you’re taking cod liver oil on a daily basis, and then you’re getting exposure to sunlight and maybe taking some supplemental D in the winter, then that’s probably where you’ll end up.  Vitamin K2 you can get from butter oil or ghee and smaller amounts from all grass-fed dairy.  Cheese is actually a particularly high source of vitamin K2, hard cheeses, and goose liver, which is I don’t think a very commonly eaten food, which again, if you’re on a Paleo diet and you’re not eating dairy and you’re not eating goose liver or natto, it’s probably a good idea to supplement with K2.

Steve Wright:  I usually eat natto and goose liver every night.

Chris Kresser:  I bet.  Natto is one of the nastiest things I’ve ever tasted.  Have you tried it?

Steve Wright:  No.  It’s on my list for 2012 to explore.

Chris Kresser:  Oh, God!  Yeah, it’s wrong.  But it’s one of those things where people either like it or absolutely can’t stand it, and that’s kind of what liver is, I think, too.  You know, either people were raised on it and they have a taste for it, or they weren’t and they can’t stand it.

Steve Wright:  Yeah, I think there’s a lot of things you can do to liver to make it taste pretty good.  I started off being a little squeamish with it, and now I actually enjoy it.

Chris Kresser:  Incidentally, I just published an article today, I mean, you won’t hear this podcast for a little while longer, so on Friday, the 6th, about why you should eat more cholesterol, and the article is about choline and the importance of choline, but at the end of the article there are several recipes for liver from some great blogs.  So, check that out if you want to get some more liver in your diet and you’re wondering about some ways to make it more palatable.  There are some good recipes there on that blog post.

Steve Wright:  So, the biggest takeaway of this A-D conversation is that if you’re just taking a D3 pill, you need to look at adding some liver or some cod liver oil to your diet?

Chris Kresser:  Yep, that’s it, and K2 also, if you’re not doing that.

Steve Wright:  All right.  Well, I think that brings us to the end here.

Chris Kresser:  Yeah, great show!

Steve Wright:  Yeah, this was good.  We dived into a lot of topics I’ve never even heard about.

Chris Kresser:  Cool.

Steve Wright:  OK, so if you’re confused about what to eat, check out the PersonalPaleoCode.  It’s a 3-step program designed to help you discover your own ideal idea and create highly customized meal plans with a few clicks of a button.  Visit PersonalPaleoCode.com to learn more.  And if you’re trying to get pregnant or are already pregnant or nursing, don’t miss The Healthy Baby Code.  It guides you through the essential steps to naturally boost fertility and promote lifelong health for you and your baby.  Find out more at HealthyBabyCode.com.

Chris and I would like to thank you for sending in your questions, and invite you to send in more questions at ChrisKresser.com using the podcast submission link.  If you enjoyed listening to the show today, head over to iTunes and leave us a review.