Low Magnesium and Depression

Hi guys.

A few blogs ago, I wrote about fish oil and depression and presented the evidence for and against.  I also described the many theories for depression that are less well known.  The “serotonin hypothesis” is the main theory  floating around out there, but there are many other theories that don’t make it into the pharmaceutical limelight.  “Depression is caused by low serotonin in the brain” is just an easy explanation to throw at people, but there really isn’t a shred of evidence that proves depression is caused by low serotonin in the brain. That is why it is the “serotonin hypothesis” and not the “serotonin definitive cause.”  I think it is  important to know about the many other theories for depression, especially if you plan on managing it holistically. If you are at all curious about them, please check out the fish oil blog.    (There’s even funny drawings by yours truly.)

Many holistic diets for managing depression include omega-three fatty acids, like fish oil, and they also include magnesium.  Some research suggests that a magnesium deficiency can lead to depression.  I supplement with magnesium for a different reason: migraines.  Magnesium is shown to help with migraines and since I am prone to migraines when I’m premenstrual, I start taking extra magnesium a week before.  Of course, since magnesium may help improve depressive symptoms, it is possible that  supplementing with it can help alleviate some of the craziness associated with premenstrual dysphoria, which is a real gem that I love to deal with every 21 days ( Insert sarcasm here. )

So, why the connection between low magnesium and depression?

Some studies indicate that magnesium is low in depressed individuals.  A causal relationship hasn’t been proven, but, really, when is it ever? Show me a honest-to-God causal relationship, and I’ll show you a correlation.   😉  But I digress.

As for magnesium and depression, here is some evidence to consider: A 2009 cross sectional  study involving 5,700 people and  conducted by Jacka et al. shows that one’s severity of depression is negatively correlated with one’s level of magnesium.  This means that the more depressed someone feels, the lower his or her magnesium levels were found to be.   A study conducted in 2008 by Iosifescu et al. shows reduced levels of magnesium in the brains of people diagnosed with treatment-resistant depression.  A 1985 study looked at magnesium levels in suicidal patients, and found it to be low. Another study conducted in 1999 by Levine et al shows that magnesium levels are low in patients who are admitted to the hospital for a depressive episode.

Animal studies have been conducted, as well.  A 2010 Austrian study by Whittle et al shows that mice who eat a magnesium-restricted diet exhibited significant depression-like behavior. Interestingly enough, those mice were responsive to SSRIs ( Serotonin Reuptake Inhibitors). In the same study, proteomics ( which simply measures levels of proteins in the body) revealed changed levels in the following proteins: DDAH was lowered; MnSOD was high; VDAC1 was high and GDH1 was high. It doesn’t matter what those proteins do. What matters is that all of those changes went back to normal after the mice were given an SSRI, which could be considered evidence for SSRIs as an effective treatment for depression.  ( I’m not a fan of them, personally, because of their side effects, but I thought this finding was interesting.)

One way that low Magnesium may lead to depression is via an increase in nitric oxide (NO).   A ridiculously simplified explanation of this theory is that Magnesium inhibits a receptor that, when active, signals a pathway that activates the enzyme, NO synthase. No synthase makes NO.  Mice that are missing the enzyme, NO synthase, show DECREASED depression-like behavior, theoretically because they are unable to create NO.  Also, a study by Mak et al. shows that a LOW Magnesium diet increases plasma levels of NO in rats.  ( Granted, we are not mice nor rats. That said, before you disregard this evidence because we are not rodents, keep in mind that we are genetically similar to rodents and many, many, many of the outcomes witnessed in animal studies are witnessed in humans as well. Science wouldn’t be anywhere without mice, so next time you see one, you should thank him instead of running away and screaming bloody Hell or trying to torture him with one of those God awful traps. )

Another interesting fact about SSRIs, Magnesium and NO: Researcher Crespi found that  SSRIs  inhibit NO Synthase, which means less NO being created in the body.  This is potentially another way SSRIs help treat depression, because why not? It’s not like anyone REALLY knows how they work. Increasing serotonin levels is just a guess.   Now I’ve just given you another guess. 😉

So I just discussed how low magnesium might produce more NO in the body and how this may lead to the symptoms of depression. Another theory of how low levels of magnesium leads to depression is the oxidative stress theory.  I mentioned earlier that one protein, MnSOD ( not a name you have to ever remember) is  high in a low magnesium diet. As it turns out, MnSOD is an anti-oxidant protein, so researchers think the fact that it is over-expressed in a low magnesium diet is because there is an increased amount of oxidative stress in the body, and therefore more of the anti-oxidant proteins, like MnSOD, are needed. Furthermore, several studies have shown that low magnesium diets  create an increased level of oxidative stress in plasma and tissues ( Astier et al. and Freedman et al.).   I’m not sure if I mentioned the “oxidative stress theory” in my fish oil blog, but that is yet another theory researchers came up with for depression. To review, an increase in oxidative stress simply means more disease-causing free radicals floating around in your body.  Free radicals have been implicated in almost every disease known to man, and that’s the reason everyone says to eat anti-oxidants. Anti-oxidants fight free radicals.

Okay, so those are two theories as to why low magnesium may create depression. Now I’m going to throw a third one at you. This theory is called the “Altered Energy Metabolism” theory.  Another grossly oversimplified explanation will follow:

Low levels of  magnesium are shown to cause reduced activity from an enzyme ( GDH1) which is  involved in the Krebs cycle, or the series of chemical reactions that creates ATP in our bodies. ATP is our body’s fuel and energy, and without it we’d all be dead.  At least two researchers, Beasley and Iosifescue, believe this resultant altered energy metabolism may manifest as depression.  ( Keep in mind that this is  the terribly stunted, blog-friendly,Depression-for-Dummies explanation.)

Now  I should clarify something I said earlier. When I say “supplement” I mean either 1) taking a magnesium supplement or 2) increasing your intake of magnesium-rich foods ( which I will list below.)   I always think it is better to get what you need through your diet rather than a pill, although sometimes the diet route isn’t always possible.   With that said, I’ll finish this blog with a list of foods high in Magnesium.  If you’re depressed, try incorporating these foods in your diet.  No matter what theory of depression you buy, more magnesium can’t hurt!


Pine nuts

Sesame Seeds

Sunflower Seeds


Watermelon Seeds






Pumpkin Seeds

Brazil Nuts

Flax Seeds




As always, email me if you have any questions.


P.S. Here is a bit of humor therapy.  So I’m in the middle of potting training, Barnaby. I’m training him to go on pee pads as well as outside. And it. is. a. chore.  I’ve come to the conclusion that rewarding him with treats when he goes outside or on the pad is not reward enough. I need to give him a treat AND sing him a song. I swear I’m not crazy, and I make up the lyrics as I go, but, hey, at least I’m making potty training a puppy fun. 😉   Here’s a video on musical potty training.

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