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Your Brain on Creatine

Creatine from meat seems to help us think.

Are you a vegetarian or a vegan? Besides vitamin B12, depending upon what you eat and the supplements you take, you can find your diet somewhat low in zinc, long chain omega 3 fatty acids, and even some amino acids. One of these amino acids is called creatine, and the best source is meat.

Researchers who study cognition and athletic performance simply love giving vegetarians creatine supplements (1)(2)(3). This practice might seem curious until you look at the following facts:

1) Creatine is an amino acid found only in animal flesh but most abundantly in skeletal muscle flesh (like steak). It is not an essential amino acid, as we can synthesize is from other amino acids found also in plant foods, but as with changing the plant-based omega 3 fatty acid ALA to the marine animal based omega 3 acid DHA, the synthesis is inefficient. It is known that vegetarians have lower tissue (measured directly via muscle biopsy) amounts of creatine than omnivores (4).

2) Why should we care if we have creatine? Well, if you recall, our cells run on energy supplied by a molecule called ATP. Think of ATP as the gasoline of the body. Whether we fuel up with glucose or ketones, eventually those raw materials get transformed into ATP, which as it is broken down powers all sorts of energy-requiring processes. We will obviously burn through ATP faster in our muscles when we are running or jumping or performing various feats of strength, but we also burn through ATP faster when we are using our noggins for something a bit complicated. Our little brain (the size of your two fists held together) burns through 20 percent of the energy we use each day, primarily to keep those ion gradients fueled that allow our neurons to charge up and then be discharged to communicate information.

3) Creatine can bind to phosphate (P) to make phosphocreatine, and this acts as a "buffer" to make ATP lickety-split. Turns out we can make ATP 12 times faster using phosphate reserves from phosphocreatine than by using the standard method of oxidative phosphorylation and a whopping 70 times faster than making ATP de novo. When we think hard, brain levels of phosphocreatine can drop pretty acutely while ATP levels stay constant, showing that we can bust into that reserve to keep our thinking sharp. In short, creatine improves brain efficiency. It is the "turbo boost" of the brain and muscles.

So let's look at these papers, shall we? In both the cognition study papers, healthy college students were recruited (colleges being both a good source of research volunteers and vegetarians) and divided into creatine or placebo supplementation groups. The British study compared vegetarians and vegan young women to omnivores, the Australian study used only vegetarians and vegans, but had a crossover design (all subjects got both placebo and creatine along the way). Both studies did various measures of cognitive and memory testing (number of words you can remember from a list read to you, how many F or P words you can say in two minutes, how many numbers you can repeat backwards from a string of numbers read to you, recognizing strings of three even or odd numbers in a series of numbers read at 100 per second). The British study added a measure of reaction time (subjects had to press a button corresponding to a light as fast as they could once it was lit). The Australian study was six weeks, the British study was five days, and both used 5g creatine monohydrate as the supplement and dextrose (glucose) as the control.

Because glucose administration has been shown to (immediately) increase cognitive performance (5), all the cognitive testing was done fasted and on a day with no supplementation.

The results? First off, everyone, vegetarian or omnivore, on placebo or creatine in the British study did worse the second time around on the memory tests (maybe they got bored?). But compared to the placebo group, the omnivores in the British study were about the same as the creatine supplement group (omnivores have been shown to benefit from a maximum of 20 grams a day at first then maintenance 2-5 grams per day supplementing for athletic performance), suggesting that us animal flesh eaters have a physiologically appropriate amount of phophocreatine reserve in the brain for interesting tasks such as pushing buttons in response to light stimuli and complicated mental tasks that involve the prefrontal cortex and the hippocampus.

The vegetarians in the creatine group did much better than the vegetarians in the placebo group on the second battery of tests involving word recall and measures of variability of reaction times. More simple mental tasks didn't improve in the vegetarians or the omnivores, suggesting, interestingly enough, that complicated thinking burns more energy than uncomplicated thinking (so do smart people burn more calories? I'm not aware of any research to that effect, in fact I thought there wasn't much of a difference, but we'll look into it ...). In some of the measures, vegetarians were higher than omnivores at baseline, by the way, and in general the memory tests between the two groups did not vary at baseline—the vegetarians just seemed to benefit much more from creatine supplementation.

In the Australian study (using only vegans and vegetarians), creatine supplementation had a significant positive effect on working memory (using backwards digit span) and intelligence measures requiring processing speed. Various cognitive tasks that were worse in the placebo vegetarians compared to creatine vegetarians are similar to those that are affected in ADHD, schizophrenia, dementia, and traumatic brain injury. In addition, people with the Apoe4 allele and therefore more vulnerable to developing Alzheimer's seem to have lower brain levels of creatine.

There. Simple. When we are not being simple, we do better with creatine.

Except there are a few wee wrinkles. It turns out that creatine supplementation seems to have an effect on glucose regulation (3)(6). Weirdly, the first study shows a higher glucose level to oral glucose tolerance load (in vegetarians), and the second study (in young athletically active males) shows a lower amount of area under the oral glucose tolerance test curve (that's good—shows increased glycemic control) with creatine supplementation. But if we consider the fact that a ready supply of glucose in the short term can improve cognitive performance, the British investigators were wondering if creatine supplementation increased glucose in vegetarians, thus increasing cognitive performance. They didn't bother to measure the glucose in the subjects, though, so who knows. In the Australian study, glucose was measured in the fasting subjects but specific levels were not reported in the paper, but it didn't seem that anyone had a high level.

In addition, creatine in the tissue doesn't necessarily equal creatine in the brain. Animal studies have shown that problems with the creatine transporter into the brain shows up as cognitive problems similar to the unsupplemented human vegetarians (compared to their supplemented vegetarian brethren). However, it is likely that the synthesis and transport mechanisms are upregulated in vegetarians (as they have low levels of creatine), so creatine might pack more punch early on for the veggies, until levels become saturated.

Well, I'm not all that interested in supplementing with creatine. But I am interested in continuing to eat steak, and in having the most efficient energy reserves available for my brain. Eating a bit of meat along the way seems like a reasonable way to achieve this goal.

Special thanks to Melissa McEwen for helping me with one of the papers, and to Jamie Scott for others.

Copyright Emily Deans, MD

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