That's a bit of a sensational title. But hey, I guess sensationalism works in the blogosphere these days (or forever in the past and forevermore), and I'm not proud.
Hacienda. Savage.
Creatine! We love creatine. There's lots of it in skeletal muscle, which we omnivores tend to eat and love because steak is oh so yummy. Vegetarians are low in it and more apt to have mental illness, at least in some observational studies. Muscleheads have been supplementing with creatine forever for muscle building and power at the gym, but some studies have shown some benefits for vegetarians and folks with Parkinson's disease. But wow, a pilot study was published the other day in the Green Journal (the best of the best of psychiatry medical journals) that could blow the door open for more applications for this supplement. It turns out the medical doctors in Utah are staging a larger follow-up study as we speak, which warrants a mention on Evolutionary Psychiatry for sure. Thanks to @AnnChildersMD for the link.
Here is the gist of the new study. A depressed brain has crappy energetics. It's inflamed and not using energy as efficiently as it could. That means ATP (body gasoline) is not being created and used as efficiently as possible. Creatine supplementation, it is well known, can juice up a superfast pathway to create new ATP by increasing the reservoirs of phosphocreatine, which provides phosphate to make more ATP (adenosine-tri-phosphate). It turns out that depressed brains that respond to treatment with SSRIs or thyroid hormones tend to have higher levels of ATP at the ready. That finding caused some researchers' brains to click to the "on" position. After all, only 60% of folks respond to antidepressant treatment (barely better than placebo). What if we augmented antidepressant treatment with creatine? (For more excrutiating details, follow some of those links in the previous paragraph.)
52 women (in mice, the effect was found to be more profound among female rodents, so female humans were used in the pilot trial to ensure the best results. I would have recommended female vegetarians, but no one listens to me much) met the criteria for inclusion in the pilot trial. They had to meet criteria for a depressive disorder, not be on antidepressants, not be pregnant, otherwise sick, etc. 1/2 the group was put on ecitalopram (lexapro) plus placebo and the other 1/2 was put on ecitalopram plus creatine (3g daily for a weeks, then 5g daily for the next 7 weeks).
Turns out the creatine supplementers responded earlier and better than the antidepressant alone group using a couple different scales (HAM-D and MADRS). The creatine group had higher response and remittance rate and no higher incidence of side effects. Sounds like a win win. Of note, SAM-e may provide a similar benefit, and it is a methyl donor which helps in the natural production of creatine.
So this was a small study, and a single study so more something to scratch your head about and take notice than for any sort of recommendations. But very interesting. I'm all for investigating the roots of brain energetics in the pathology of major depressive disorders, and finding inexpensive and practical solutions to make lives with depression better faster.
The one time I took creatine I got a migraine as a result (I used to be prone to migraines but hadn't seen one in years). Which may be relevant - it definitely affected my brain.
ReplyDeleteOh, I just remembered; creatine is able to quench peroxinitrite. Hydroxycobalamin also binds to peroxynitrite, so quench peroxynitrite with creatine instead and you automatically improve methylation. Which improves the neurotransmitter balance in this case.
ReplyDeleteThat would be a mechanism.
Hi Dr. Deans,
ReplyDeleteTHe variety of data on creatine's effect on cognition alone or under sleep deprivation, coupled with the different dosing patterns and experimental populations has made it difficult to understand a means of optimal implementation. I was wondering if you had any data or knowledge to reconcile the data that at least suggests the possibility of needing more creatine than the amount found in meat for former vegetarians (e.g. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1691485/pdf/14561278.pdf --shows a steep drop off during the washout and crossover to placebo; the total creatine content over 6 weeks seems to be roughly 210g, which is A LOT of meat to eat )
I hesitate to go there considering the state of the literature. However, speaking abstractly, it would make sense for conditions such as Parkinson's disease (and dare I say depression???) that meat alone would not be sufficient.
DeleteWhat really gives me pause is the idea of going without any dietary creatine at all, a la veganism, and how that might affect brain energetics.
Since doctors seem to be more likely to indulge the vegetarian/vegan life, I would dare say replace the coffee stand with some creatine laced water for the meat hating, sleep deprived physicians =)
DeleteCreatine-laced water certainly does minor wonders for the sorry state of my (depressed) brain; unlike a few other substances I've tried out it really seems to supply needed energy, not ameliorate symptoms.
DeleteAre there any other ways of ramping up ATP production/aiding the creatine in its function?
Very interesting. I'm wondering if the Utah study will pay to have a group that takes creatine by itself without the antidepressant. At less than $9/lb, creatine is hard to beat.
ReplyDeleteIs it advisable to supplement with creatine if i eat a diet with lots of animal protein (beef, chicken, eggs, fish) daily? (Context: Formerly prone to depression and anxiety, now living fairly well SSRI/SNRI-free (i.e. meds-free) after five months. Strength-training workout twice a week, one hour each.)
ReplyDeleteGroovy music Emily, I ate a vegan diet for a bit....what a disaster I was. Meat and supps have made me feel better. I love this blog and the stance you take, wish there were more of you.
ReplyDeleteOf course a vegan diet would be deficient in both creatine and hydroxycobalamin. The latter is also required for the synthesis of creatine. The antioxidant level of the diet (or the overall effect of the diet on oxidative stress) might compensate for this in some cases (sparing what creatine and B12 are present). Ascorbate is also required for creatine synthesis; one would hope that a vegan diet would be replete in ascorbate, but most vegans I've known seem to eat junk food without the meat. Or maybe it's health food - I find it hard to tell the difference.
ReplyDeleteAh, Sam-E. Use with caution...
ReplyDeleteSome years back I decided to try Sam-E for my persistent low grade depression. Around the same time I was barely sleeping due to a periodontal abcess that wasn't responding to antibiotics. Full blown manic episode and hospitalization followed shortly thereafter. I had never shown any signs of mania before or after. I didn't consider Sam-E as the trigger until years later when I mentally reconstructed the events and did more reading about this --not exactly innocuous--"supplement". Lucky me, diagnosed bipolar. Am slowly tapering Depakote with my pdoc's oversight, much better mental function and quite stable. I am 47.
I haven't tried creatine because I've read a LOT of anecdotal stuff on it causing energy and anxiety (however, I see lots saying it HELPED with anxiety and low-energy too). I generally avoid anything that "causes" energy (even though I'm always tired) because anything that gives me energy tends to increase my anxiety (panic disorder). I don't even touch caffeine, so I figured creatine was probably out of the question.
ReplyDeletei'm a vegan, gluten free and will be a kinda paleo without the meat wheni have taken sugsr out of my diet. On hearing about Creatine, i researched and found (on Wickipedia that creatine is produced by the body using building block-amino acids that make up protein; Methionine, glycine, Arginine. Then i researched that these amino acids are found in quite large amounts in seeds, primarily sesame, so my question is can a vegan avoid a creatine defficiency with sesame seeds?
ReplyDelete