3 Ways to Reduce Brain Fog

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Does too much dietary protein make your brain fog worse? Does gut-related symptoms worsen your brain fog?

Problems with ammonia clearance may be at play. Some ME/CFS metabolomics studies suggest faults in the urea cycle, the body’s pathway to clear ammonia. Other sources of ammonia include over production of the potentially toxic compound by our own gut bacteria. Any intervention that enhances healthy ammonia clearance may therefore reduce brain fog. Read more about potential causes of brain fog in a previous post.

Minimal hyperammonia can be detected best by using stool or urine studies. Plasma ammonia may not be predictive of the gut environment nor sensitive enough to detect very low level ammonia increases. Minimal elevations in ammonia may even be difficult to detect by traditional, gold-standard electroencephalopathy (EEG).

Promoting Bifidobacteria & Reducing Ammonia Producing Bacteria

Ammonia can be sequestered by using supplemental fiber products. Indeed, these interventions are first-line options for those with high ammonia due to liver disease. Non-absorbable disaccharides, such as lactulose and lactitol are commonly used. Formulas that contain inulin fiber—from chicory, dandelion, or burdock root—have also been used in various studies. These laxatives promote growth of bifidobacteria, which actively works to sequester ammonia. Supplemental bifidobacteria using probiotics alone is unlikely to provide adequate treatment due to problems with probiotic delivery and the sheer volume that would be required to alter populations. In more severe cases of intestinal dysbiosis, a short course of rifaximin may be used to eliminate ammonia producing gut bacteria.

Dietary Ketones

Brain fog may also be driven by an imbalance of amino acids in the central nervous system. Most vital is the balance of glutamate and glutamine. Glutamine is the amino acid precursor to the neurotransmitter glutamate which is classically excitatory. Tight checks and balances are required to regulate glutamine and glutamate. It is thought that glutamine’s conversion to glutamate and excitatory effects on neurons can result in neuroinflammatory processes and therefore symptoms of brain fog.

Crucial to reducing brain fog of glutamine/glutamate imbalance is modulating the enzyme glutamine synthase. This enzyme utilizes glutamate and ammonia to form glutamine. The enzyme essentially sequesters ammonia and is therefore crucial in reducing even subtle ammonia elevations in the brain. Ketones, such as beta-hydroxybutyrate, upregulate the enzyme glutamine synthase. Ketones produced via dietary means thus reduce excitatory brain glutamate, reduce ammonia, and promote production of glutamine. This mechanism may underlie the positive effects of ketogenic diets on epilepsy, bipolar disorder, and improved cognitive function in neurodegenerative diseases like Parkinson’s and Alzheimer’s.

ALCAR Supplementation

Acetyl-L-carnitine (ALCAR) has been used in numerous randomized, double-blind, placebo-controlled trials to reduce ammonia load and improve cognitive function in those with liver disease. ALCAR plays a key role in transferring energy from food stuffs, long-chain fatty acids, into the mitochondria where it is converted to cellular energy. Because of this, ALCAR is often considered a supplement for improved energy production.

However, it also plays a key role in the brain where it may reduce brain fog. ALCAR can cross the blood-brain barrier where it provides its acetyl-group (the “A” in ALCAR) to pathways involved with oxidative stress, free radicals, and neurotransmitter production. Some studies suggest that ALCAR deficiency leads to increased systemic ammonia levels. ALCAR supplementation in doses up to 2g per day reduces ammonia better than placebo in several RCT’s, while also improving memory and recall.

 

Ruskin DN & Masino SA. (2012) The nervous system and metabolic dysregulation: emerging evidence converges on ketogenic diet therapy. Front Neurosci. 2012 Mar 26;6:33.

Sharma,P., Sharma,B.C., Puri,V., Sarin,S.K. (2008)  An Open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol. 20, 506–511.

Jin YY, et al (2018) Blood Ammonia as a Possible Etiological Agent for Alzheimer's Disease. Nutrients. 10(5). pii: E564.

Ota. M, et al. (2019) Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer's disease. Neurosci Lett. 690:232-236.

Malaguarnera M. et al. (2007) Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci. 52(11):3259-65.

Malaguarnera M. et al (2008) Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci. 53(11):3018-25.

Maldonado C. et al (2016) Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia. Biomed Res Int. 2016:2920108.

Dr. Craigbrain fog, ammonia