Consider the contribution of the gut microbiome in these functions. A highly processed "Western diet" leaves little behind to feed the beneficial microbiota we are learning play a significant role in physiological functioning (particularly in regulation of the immune system). The gut-brain axis, mediated by direct vagal communication as well as circulating hormonal factors, also communication regarding what we eat and when we eat and our higher order brain functions that mediate these behaviors. The gut microbiome has been considered as a modulating factor in the development of autism, and with your personal interest in that disease, I suggest you look into it further.

Connection that I came to know about diet and brain function is “behaviour”. Individual’s behaviour in terms of habit / addiction is found to be directly or indirectly associated with genetic as well as other environmental factors. For example, dopaminergic pathway in the mesolimbic ventral tegmental portion of the brain is influence by drug (alcohol, cocaine etc) through neurotransmitter system resulting different functions like reward, desire, emotional etc. There are several literatures supporting such findings. Moreover, one carbon metabolism pathway also shows important relationship between diet and brain functions. Like deficient of low micronutrients such as vitamin B12 and folate cause hyperhomocysteinemia which further leads to certain diseases related with abnormal brain functions. For understanding the exact physiology, I think a comprehensive study including high throughput brain imaging techniques, neuroscience, molecular biology etc. would be more meaningful.

Huldrom: I appreciate your feedback. I agree that homocysteine is an under-appreciated factor when it comes to brain function. If your homocysteine is high, it's a sign your brain isn't getting enough folic acid because the only form of folic acid that can cross the blood-brain barrier is L-methyfolate. The simple work around is to take L-methylfolate as a supplement. In the US it is approved for treatment of depression under the brand name Deplin.

We also believe that processed food can adversely affect the brain by causing a form of food-induced food dysfunction called Carbohydrate Associated Reversible Brain syndrome or CARB syndrome. I blog about this topic at:

http://carbsyndrome.com/

I"m presently working on Alzheimer's disease (AD) and my researches are focusing on factors which are contributing to its pathogenesis namely hypercholesterolemia. I'm interested on how the neurovasculature participate in the neurovascular coupling implicated in the blood-brain barrier (BBB) functionality. Hypercholesterolemia contributes to increase low-density lipoprotein (LDL) levels in blood circulation. It is recognized that LDL with reactive oxygen species (ROS) formed oxidized LDL which are implicated in atherosclerosis, a vascular pathology contributing in brain hypoperfusion. This phenomenon is strongly associated with BBB dysfunction which is observed at early stages of AD pathogenesis. BBB is a major system implicated in central nervous system (CNS) detoxification and nutrients supply to ensure an healthy environnement for neurons. In this context, the western diet which contributes to hypercholesterolemia is implicated in BBB dysfunction and consequently in AD pathogenesis. There is a connection between diet and brain: the diet can acts directly on CNS homeostasis by altering the neurovasculature functionality, and consequently impact on behaviour (e.g. cognitive functions) as seen in AD patients.

What do you think about ketogenic diets (eg. low carb and high in medium chain fatty acids)? I know a low carb diet has been used for childhood epilepsy. I don't know the mechanism underlying these anti-epileptic effects but I think it is likely related to the fact that the brain switches to use more beta-hydroxybutryate and less glucose in this context.

This is a very important question, which is often overlooked. Basically, every substance from the food that penetrate BBB could affect brain function (also those that first methabolized and then could penetrate BBB ). There is a good book, although rather old (2002), that discusses some findings regarding this topic: "Diet - Brain connections: Impact on Memory, Mood, Aging and Disease", by Mark Mattson.

Johnathan: A ketogenic diet appears to have neuroprotective properties that might be helpful for a long list of brain disorders. We need larger controlled studies but the preliminary evidence is interesting. My friend Tom Seyfried is doing research on using ketogenic diets for cancer:

http://www.bc.edu/schools/cas/biology/facadmin/seyfried.html

There are likely many ways that dietary elements can adversely affect brain function. Insulin resistance (type 3 diabetes) likely plays a role. Postprandial glucose spikes in an environment of insulin resistance also likely contribute to neuron dysfunction because neurons don’t have an insulin gate, leading to oxidative stress, glycation and mitochondrial dysfunction. An abnormal balance of omega 6 to omega 3 fatty acids also likely affects membrane function.

The Wurtmans’s from MIT showed that postprandial glucose spikes following consumption of high glycemic carbohydrates cause an increase and brain serotonin but we think this may be pathological rather than physiological where neurotransmitters are “dumped” following these glucose spikes. This can eventually lead to a depletion of neurotransmitters.

Excessive fructose from sugar and HFCS is likely driving insulin resistance. Thus excessive fructose, high glycemic carbohydrates especially from grains and excessive omega 6 fatty acids from vegetable oils seem to be key drivers of brain dysfunction. This of course describes typical processed food.

Consider the contribution of the gut microbiome in these functions. A highly processed "Western diet" leaves little behind to feed the beneficial microbiota we are learning play a significant role in physiological functioning (particularly in regulation of the immune system). The gut-brain axis, mediated by direct vagal communication as well as circulating hormonal factors, also communication regarding what we eat and when we eat and our higher order brain functions that mediate these behaviors. The gut microbiome has been considered as a modulating factor in the development of autism, and with your personal interest in that disease, I suggest you look into it further.

Brittany:

I agree. There are three main nodes that interact when it comes to diet and the nervous system. The first node is the CNS, the second is the ENS and the third is the microbiome. In my opinion processed food has a direct adverse affect on all three nodes and when one is adversely affected, the others suffer downstream affects.

Brittany:

I recently published this paper on nutrition and autism:

http://najms.net/v06i03p158w/

My friend Aaron Blaisdell is also doing animal research on the effects of processed food on brain function:

http://www.ancestralhealth.org/post/ahs13-poster-presentations

I think this will be a very active area of research in the future.

Dear colleague I suggest reading this interesting review on Tryptophan and serotonin:

Effects of tryptophan loading on human cognition, mood, and sleep Silber and Schmitt Neuroscience and Biobehavioral Reviews 34 (2010) 387–407

Pamela:

Yes, tryptophan loading is interesting, but 5-htp has many therapeutic advantages over tryptophan. It doesn’t require a transport molecule for absorption and thus its absorption is not affected by the presence of other amino acids. Thus it can be taken with or without food. Unlike tryptophan it cannot be shunted to niacin or protein production. Unlike tryptophan it also doesn’t rely on the rate limiting enzyme tryptophan hydroxylase and it readily crosses the blood brain barrier. Thus consumption of 5-htp directly increases brain serotonin levels.

After treating thousands of patients it became apparent to us that if you give someone just 5-htp, their dopamine and norepinephrine levels tend to drop. If you combine the precursor L-tyrosine with 5-htp, then all the monoamine neurotransmitters rise together. A ratio of L-tyrosine to 5-htp of 10 to 1 seems to work the best. I have used this type of mixed precursor supplement for decades to help treat a broad range of brain problems.

By the way, consumption of highly processed foods seems to deplete these neurotransmitters, so eating a whole food diet is also beneficial in maintaining healthy brain function.

There are many misinterpreted points in the diet-brain link. One of the worst is a lack of common language, especially in diet definitions. I suggested (see reference below) to recall a criterium, which is in use for a century - but is missing in most research methods. Even lab animal's feed intended to study the role of macronutrients (like in obesogenic diets) is lacking succinct definition. I had to recalculate the standard lab diets to figure out what they really are and figured that what's called high-fat diets are in fact high-fat + high-carb. Truly high-fat diets are neuroprotective, cardioprotective and canceroprotective. With high carb content, they are just opposite.

To read more:

http://www.frontiersin.org/Journal/10.3389/fnene.2011.00008/full

http://www.frontiersin.org/Journal/10.3389/fnene.2012.00007/full

Tanya—Thanks for pointing out this important principle. When you combine fat and carbohydrates (modern processed food) you end up with metabolic problems and you also fry your brain. In order to protect your brain function you need to limit carbohydrates. Ketogenic diets are likely neuroprotective because they limit carbohydrate intake.

Ketogenic diets have also been used for various other brain disorders. They were first developed at the Mayo Clinic to treat seizures. Thomas Seyfried is now using them to treat brain cancer:

http://www.bc.edu/schools/cas/biology/facadmin/seyfried.html

These remarkable results are achieved by limiting carbohydates.

There are so many aspects to consider, but one thing I like to think about is microglia as players in the brain-nutrition game. Microglial activation, an indicator of what microglia are doing, is very much affected by diet. But its very complex. For instance, food restriction affects microglial activation in some brain areas but not others. (if you want some specifics, in one study, it lessened age-related increases in complement receptor expression but not MHC-II expression in microglia in basal ganglia; yet food restriction and age did not affect these two measures in the outer molecular layer of the dentate gyrus.)

With thiamine deficiency, likely in alcoholics or nutritionally deprived people, ATP may be unavailable or lactate may accumulate with reduced thiamine dependent enzymes. Like all cells, microglia depend on energy, thus can become dysregulated by metabolic compromise, being exquisitely sensitive to it, changing both their profile of proteins expressed and their morphology. They have roles in normal brain functioning as well as pathological monitoring, so the roles from there you can imagine.

I bet somebody here will know more about microglia and nutrition, but anyway here are some general refs:

Front Cell Neurosci. 2013 Jan 30;7:3. doi: 10.3389/fncel.2013.00003. Quantitating the subtleties of microglial morphology with fractal analysis.

Karperien A, Ahammer H, Jelinek HF. http://www.ncbi.nlm.nih.gov/pubmed/23386810

Todd, KG & Butterworth, RF 1999b, 'Early microglial response in experimental thiamine deficiency: an immunohistochemical analysis', Glia, vol. 25, no. 2, pp. 190-8.http://www.ncbi.nlm.nih.gov/pubmed/9890633

Morgan, TE, Xie, Z, Goldsmith, S, Yoshida, T, Lanzrein, AS, Stone, D, Rozovsky, I, Perry, G, Smith, MA & Finch, CE 1999, 'The mosaic of brain glial hyperactivity during normal ageing and its attenuation by food restriction', Neuroscience, vol. 89, no. 3, pp. 687-99. http://www.ncbi.nlm.nih.gov/pubmed/?term=10199605

Calingasan, NY & Gibson, GE 2000a, 'Vascular endothelium is a site of free radical production and inflammation in areas of neuronal loss in thiamine-deficient brain', Ann N Y Acad Sci, vol. 903, pp.

353-6.