Butyrate & BDNF for Brain Health

The number of people with Alzheimer’s disease (AD) or other dementia is expected to soar with the baby boomer generation.  The 2016 report by the Alzheimer’s Association reveals the alarming trend:

  • Alzheimer’s already affects 5 ½ million Americans (and their caregivers)
  • By 2050, it’s expected to rise to 14 million people
  • Medicare spends 2.5 times more $ on people with dementia diagnosis
  • Total healthcare payments for 2016 alone, were $230 billion
  • Alzheimer’s can bankrupt families, as Medicare does not pay for nursing home care

Recent research is pointing to gut health and systemic inflammation as major determinants of brain health.  An article in the Journal of Alzheimer’s Disease recently said, “bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides”.  The article further explained that this scenario leads to systemic inflammation associated with obesity, diabetes and Alzheimer’s. Another respected journal, the Lancet, echoed this finding, “systemic inflammation and obesity are likely to interfere with immunological processes of the brain and further promote disease progression”.

by VSRao at Pixabay

It is critical to learn and use the best practices for brain health.  Two substances that naturally occur in the body, butyrate and BDNF, are essential for a healthy and functional brain. Butyrate and BDNF enhance cognition and protect the brain from decline. Simple choices that you can make today, will give you access to butyrate and BDNF.

Gut-Brain Axis

Butyrate is a multi-functional molecule with regulatory effects on immune response, metabolism and vagus nerve activity.  The vagus nerve is the pathway of communication between the brain, the gut and the microbiome (the trillions of organisms and their genetic material).  People mistakenly assume that the brain is directing the functions of the body, in a top down approach. However, the vagus nerve transmits many more signals originating in the gut, up to the brain.  In fact, for every one signal coming down the vagus nerve, there are seven signals going from the gut to the brain. The signals going to the brain depend on the composition of the microbiota (the mix of organisms living in the gut) and the substances produced by those organisms.  Understanding this bi-directional flow of signals helps us to see how gut health and the microbiota significantly affect the brain.


Butyrate exerts a protective role.  It helps the body to resolve the metabolic imbalance and inflammation that leads to brain degeneration. Research has shown specific benefits of butyrate in human and animal studies:

  • HDAC inhibitor (allows body to destroy damaged or cancerous cells)
  • Reversal of insulin resistance (risk factor for diabetes)
  • Decrease visceral adiposity (belly fat)
  • Prevent colon cancer
  • Lower triglycerides and LDL
  • Reduce appetite and prevent obesity
  • Protective against Parkinson’s

 See “Sources” below for links to butyrate research.

How do we get butyrate?

Butyrate is a short-chain fatty acid, produced in the colon by commensal bacteria.  The bacteria require a constant supply of fiber from the diet, which they ferment to produce butyrate and other short chain fatty acids.

Resistant Starch The food highest in resistant starch are white beans (navy, cannellini and northern).  Resistant starch develops in potatoes and sushi rice, after it is boiled and then cooled in the refrigerator, prior to consumption.  (The potatoes still retain the resistant starch when reheated.) This preparation technique is particularly important for anyone with blood sugar issues.  Other great sources of resistant starch are unripe bananas, teff, raw oats, peas, beans, barley and millet. Teff and millet are nutritious grains that are gluten-free.  Teff is quite enjoyable as Ethiopian injera, a soft flatbread.

Bacillus Bacteria Research on bacillus species show they improve microbiota diversity in the gut, even after a short time of supplementation.  In particular, Bacillus coagulans has been found to promote several beneficial bacteria in the colon, F. prausnitzii in particular, leading to higher production of butyrate.  Restoring microbiota diversity is critical in our modern times of excessive antibiotic exposure from prescriptions, conventionally raised meat and dairy, and produce laden with pesticides.

BDNF: Brain Derived Neurotrophic Factor

In a study published by the Journal of Neurology, researchers confirmed that higher levels of BDNF results in slower cognitive decline.  Another study in the Journal of American Medical Association, following 2,000 adults aged 60 or older, also found that people with the highest levels of BDNF had the lowest risk of Alzheimer’s or dementia.  Brain derived neurotrophic factor (BDNF) is a protein created by the body that enhances neurogenesis (creation of new brain cells) and neuroplasticity (creating new connections between brain cells).

How do we increase BDNF?

Intermittent fasting increases BDNF while reducing the inflammation caused by bacterial infection or gut dysbiosis. (The Journal of Alzheimer’s Disease recently confirmed the connection between the gut microbiota and brain inflammation.) In clinical studies, various fasting schedules have been tested:  24 hours every other day or daily fasting for 16 hours, with feeding window of 8 hours.
Exercise and aerobic activities that elevate heart rate, lead to higher BDNF production.  Both fasting and exercise exert temporary stress, which promotes autophagy (cellular cleanup), DNA repair, and new synaptic connections between neurons.  Aerobic exercise is the best strategy for increasing BDNF and protecting the brain.

by Stevepb at Pixabay

Curcumin, one of the bioactive substances in turmeric, is a well known for its anti-inflammatory effects throughout the body.  Among its many health benefits, curcumin is neuroprotective. Both human and rodent studies have shown increases in BDNF with regular supplementation of curcumin.

by Daniel Reche at Pexels

Coffee Fruit Extract in the preliminary stages of research, has shown positive effects on BDNF.  In one study, whole coffee fruit extract was effective at increasing BDNF by 143%. (This is not the same as green coffee extract.)

“Put It into Practice” Resources

Fasting – Many people are not accustomed to fasting, but it’s an important healing strategy that has been used for centuries.  You can learn more about fasting from doctors who use it with their patients, during the Fasting Summit, starting on January 14th.

photo courtesy of Pixabay

Aerobic Activity – Given that this strategy is free, there is no excuse not to use it.  Every person can add some activity to their day and build on it over time. There is such a wide variety of activities to choose from, it doesn’t have to involve a gym membership.  Finding an activity that offers enjoyment is the key to long term sustainability.

Resistant Starch – Increasing intake of RS is easy and affordable.  When purchasing precooked beans, look for organic white beans in non-BPA cans. Experiment with whole grains such as millet and teff. Millet is cooked like rice and has a neutral flavor.  We prefer Anthony’s Goods as a supplier, who also offers interesting recipes with teff flour.

Gut Health – certain Bacillus bacteria improve gut function and microbiota diversity. Just Thrive probiotic provides DNA-verified strains of Bacillus which have been tested in clinical studies.

Curcumin – Buy a high quality supplement, or don’t bother.  Poor quality supplements do more harm than good. Ayush Herbs is standardized to 97% curcuminoids, produced in a certified GMP facilty, 3rd party tested for heavy metals, and grown without herbicides or pesticides. Note: people using medications must work with a health practitioner to verify if curcumin will interact with their medications.

We now know that Alzheimer’s is NOT simply a genetic disease. Alzheimer’s is a preventable disease. In fact, researchers tell us that over 50% of Alzheimer’s cases are the result of “modifiable factors,” including hypertension, diabetes, obesity, physical inactivity, and smoking. Each of these factors is the result of our lifestyle choices. What lifestyle choices are you making? What is one change that you can implement today?

Check out our related article on Alzheimer’s drugs.

Sources on Alzheimer’s Disease trend:

  1. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016 Apr;12(4):459-509.
  2. The Gut Microbiota and Alzheimer’s Disease.  J Alzheimers Dis. 2017;58(1):1-15. doi: 10.3233/JAD-161141.
  3. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015 Apr;14(4):388-405. doi: 10.1016/S1474-4422(15)70016-5.
  4. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28. doi: 10.1016/S1474-4422(11)70072-2

Sources on Butyrate:

  1. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016 Oct;99:110-132. https://doi.org/10.1016/j.neuint.2a016.06.011 
  2. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015 Apr 14;7(4):2839-49. doi: 10.3390/nu7042839.
  3. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? Neurosci Lett. 2016 Jun 20;625:56-63. doi: 10.1016/j.neulet.2016.02.009
  4. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit. Gut. 2018 Jul;67(7):1269-1279. doi: 10.1136/gutjnl-2017-314050
  5. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240
  6. Sodium butyrate exerts protective effect against Parkinson’s disease in mice via stimulation of glucagon like peptide-1. J Neurol Sci. 2017 Oct 15;381:176-181. doi: 10.1016/j.jns.2017.08.3235
  7. Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086.Anaerobe. 2014 Dec;30:75-81. doi: 10.1016/j.anaerobe.2014.09.00

Sources for BDNF:

  1. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology. 2016 Feb 23;86(8):735-41. doi: 10.1212/WNL.0000000000002387.
  2. Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol. 2014 Jan;71(1):55-61. doi: 10.1001/jamaneurol.2013.4781
  3. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.  J Neuroinflammation. 2014 May 6;11:85. doi: 10.1186/1742-2094-11-85.
  4. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway.  J Mol Cell Cardiol. 2009 Mar;46(3):405-12. doi: 10.1016/j.yjmcc.2008.10.027
  5. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance. Free Radic Biol Med. 2017 Jan;102:203-216. doi: 10.1016/j.freeradbiomed.2016.11.045
  6. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial. Neuropeptides. 2016 Apr;56:25-31. doi: 10.1016/j.npep.2015.11.003
  7. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. J Clin Psychopharmacol. 2015 Aug;35(4):406-10. doi: 10.1097/JCP.0000000000000352.
  8. Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway. PLoS One. 2015 Jun 26;10(6):e0131525. doi: 10.1371/journal.pone.0131525.
  9. The Neuroprotective Effect of Curcumin Against Nicotine-Induced Neurotoxicity is Mediated by CREB-BDNF Signaling Pathway. Neurochem Res. 2017 Oct;42(10):2921-2932. doi: 10.1007/s11064-017-2323-8. Epub 2017 Jun 12.
  10. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. Br J Nutr. 2013 Aug 28;110(3):420-5. doi: 10.1017/S0007114512005338. Epub 2013 Jan 14.

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