Intermittent Fasting, BDNF, Depression, More

Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. Duan W, Lee J, Guo Z, Mattson MP. J Mol Neurosci. 2001 Feb;16(1):1-12. [FREE FULL TEXT]

Abstract
Dietary restriction (DR) increases the lifespan of rodents and increases their resistance to several different age-related diseases including cancer and diabetes. Beneficial effects of DR on brain plasticity and neuronal vulnerability to injury have recently been reported, but the underlying mechanisms are unknown. We report that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex, and striatum of rats maintained on a DR regimen compared to animals fed ad libitum (AL). Seizure-induced damage to hippocampal neurons was significantly reduced in rats maintained on DR, and this beneficial effect was attenuated by intraventricular administration of a BDNF-blocking antibody. These findings provide the first evidence that diet can effect expression of a neurotrophic factor, demonstrate that BDNF signaling plays a central role in the neuroprotective effect of DR, and proffer DR as an approach for reducing neuronal damage in neurodegenerative disorders.

My comments:

This paper dated in 2001 was written before “intermittent fasting” became a thing, so the results were a little hidden under the title “dietary restriction” but these rats were fasting nonetheless. One of the study authors here is Mark Mattson who did the TED talk on fasting and brain power. BDNF (brain derived neurotrophic factor) isn’t particularly catchy in the literature but appears immensely important to aging well, maintaining memory, preventing Alzheimer’s. So these findings relate to a lot of potential health benefits that are apparently easily achieve and underutilized.

What I thought was most fascinating from the paper wasn’t just intermittent fasting increases BDNF, but rather how much it increases, which wasn’t just “statistically significant” but was EXTREMELY SUBSTANTIAL! Three months on an alternate day diet increased BDNF increased hippocampal BDNF ~519%. Brain researchers are apparently especially interested in hippocampus BDNF and nerve growth because atrophy and decline is especially associated with depression disorder, brain aging, memory loss and Alzheimer’s disease. There are even associations of low BDNF seen in anxiety disorders.

There are a number of ways to increase BDNF and I first read about it in the book Spark, which was a great book about the effects of exercise on the brain. It had a chapter on depression and how aerobic exercise in particular increased BDNF and decreased depression symptoms. I had also read about BDNF due to my interest in electric stimulation for headaches, which then got me reading about electroconvulsive therapy (ECT), which is said to be the single most effective treatment for major depression disorder, for which a major pathway in which it is thought to work is by increasing BDNF and therefore new neuron growth in the hippocampus. A recent paper just looked at combining ECT with aerobic exercise and they found the effects to be additive, thus both ECT and exercise worked, but the combination worked better with regards to both increasing BDNF and decreasing symptoms. The downside of ECT doesn’t seem to be the ECT itself so much, but that it requires the patient to go under general anesthesia, each and every time over the course of the treatment, which regardless of effectiveness sounds like a bit of an ordeal.

This paper also found the increases in BDNF were more widespread than just the hippocampus and rather increased in all parts of the brain in which they looked. Cerebral cortex BDNF was increased ~150%, and straitum BNDF increased ~282%. Nerve growth factor (NGF) was also increased with alternate day eating being increased ~64% in the hippocampus, 70% in the cortex and 89% in the straitum.

As I read more and more papers about people using fasting, either intermittent or prolonged for weight loss, there are very frequent reports of improved well being and sometimes “frank euphoria” among the fasters. I had previously thought the ‘high’ you get from fasting was due to the increase in endorphins, and I’m sure part of it is, but it looks like BDNF and subsequent neurogenesis might also be part of it, particularly in the long term. So far I have not seen anyone put two and two together looking at intermittent fasting and mental health, but with major depression and associated disorders continuing to be such a problem, thinking inside the box is likely a sub-optimal strategy. It certainly looks worth a try, and combined with aerobic exercise might be a powerful long term fix that may lessen reliance on drugs which have serious side effects and are of debatable effectiveness. The side effects of intermittent fasting seem to be that you look better, age slower, and die older.

So if you haven’t tried it, try it, you’ll probably feel better.

As always, if you have any further questions or need for clarifications, please don’t hesitate to ask. Being aware that some of my blog ideas are contentious and occasionally a bit out of the field of my expertise, I encourage my readers to come forth with any questions/comments that are of interest or concern. Your comments are valued and welcomed.

Chad Reilly is a licensed physical therapist, located in North Phoenix, practicing science based medicine with treatment protocols unique and effective enough to serve patients from Phoenix, Scottsdale, Mesa, Chandler, Tempe, Peoria, and Glendale.

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