Can NMN Improve Brain Health in Diabetics? A Look at Recent Research

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A recent study found that nicotinamide mononucleotide prevented cognitive decline in diabetic rats.

With over 5 million Americans living with Alzheimer’s disease and many more with pre-clinical symptoms of memory loss, researchers are hopeful to discover therapies to prevent this increasingly prevalent cognitive decline. 

Recently, researchers have given more attention to the association between diabetes and Alzheimer’s disease (AD); in fact, AD has been referred to as “type 3 diabetes”. 

As excess sugar in the bloodstream is the leading cause of diabetes, it’s hypothesized that excess sugar in the brain is also a cause of cognitive impairment. High blood sugar in the brain is linked to inflammation, neurodegeneration, and an increase in amyloid-beta plaque buildup, a hallmark of AD development.

Due to the growing evidence linking diabetes and AD, a recent study aimed to determine how to prevent or reverse this diabetes-induced cognitive impairment, using the molecule nicotinamide mononucleotide, or NMN. In this article, learn more about the details of this research and what they discovered about how NMN may be used in the future to prevent cognitive decline. 

What Is NMN? A Recap

Nicotinamide mononucleotide is a precursor to the coenzyme NAD+ (nicotinamide adenine dinucleotide), which is necessary for the survival and function of all human cells. 

With age, NAD+ levels naturally decline; this decline is implicated in chronic disease development and premature aging. Maintaining elevated levels of NAD+ is linked to healthier cells, and an increase in both lifespan and healthspan — the years lived healthfully and disease-free.

Although NAD+ can be taken supplementally, it is not the most efficient way to raise NAD+ levels. Instead, the precursor NMN directly enters cells and converts into NAD+, effectively boosting levels of this crucial coenzyme. 

In addition to increasing longevity, NMN may reduce the risk of neurodegenerative diseases and improve cardiovascular and metabolic disorders. 

Can NMN Prevent Cognitive Impairment? Recent Research

Published in the International Journal of Molecular Sciences in June 2020, this study used an animal model to assess NMN’s effects on diabetes-related cognitive impairment. 

What Did The Study Look At?

Researchers analyzed several biomarkers and cognitive tests before and after inducing rats with type 2 diabetes. The diabetic rats had significantly higher hippocampal glucose and glutamate levels, with reduced levels of the antioxidant glutathione. 

The diabetic rats also experienced memory deficits and significant decreases in hippocampal CA1 neurons, which are necessary for the formation, consolidation, and retrieval of memories. 

After the initial measurements and tests, 100 mg/kg of NMN was given to some of the rats subcutaneously on alternating days for three months. 

There were four groups: 

  1. Diabetic rat control
  2. Non-diabetic rat control
  3. Non-diabetic rats with NMN administration
  4. Diabetic rats with NMN administration, also known as the treatment group. 

To assess brain biochemistry changes, the researchers used localized high-resolution proton magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) on the hippocampi of the rats.

MRI brain scans found that NMN prevented neuron loss in diabetic rats.

What Did the Researchers Find? 

After administering NMN to the diabetic and cognitively impaired rats, the results were encouraging. The researchers found that:

1. NMN Normalized Brain Chemicals

The treatment group experienced significant decreases in glutamate, an excitatory neurotransmitter implicated in Alzheimer’s disease when found in excess. 

Also, NMN increased glutathione levels, the body’s master antioxidant that reduces free radicals and oxidative damage. Brain glutathione levels tend to be significantly lower in patients with neurodegenerative diseases.

2. NMN Prevented Hippocampal Neuron Loss

In the diabetic rats without NMN supplementation, there was a 40% reduction in the CA1 neurons in the hippocampus. In rats with NMN supplementation, both the volume and number of hippocampal CA1 neurons were increased significantly, thereby reversing the diabetes-related decline in neuronal health. 

The CA1 region of the brain is involved in learning, cognition, and memory; the neurons in this area are especially vulnerable to damage from injury, excess glutamate, or hyperglycemia. Loss of hippocampal CA1 neurons is a cause of memory impairment in dementia.

3. NMN Prevented Diabetes-Induced Memory Loss 

The researchers analyzed memory loss using cognitive tests, including a maze that assessed short-term spatial memory. The treatment group experienced significantly improved scores on these tests. 

Spatial memory is highly dependent on hippocampal function. The increase in hippocampal neuron count and volume after NMN supplementation likely played a large role in improving these memory scores. 

4. NMN Improved Mitochondrial Respiration 

In diabetics, the high glucose environment inhibits mitochondrial function, which increases oxidative stress and cellular workload. This increase in workload decreases maximal oxygen consumption rate and spare respiratory capacity to the brain, leading to neurodegeneration. 

The researchers measured respiration in the hippocampal mitochondria and found that maximal oxygen consumption and mitochondrial spare reserve capacity significantly increased after NMN supplementation. 

These results indicate that NMN protected the mitochondria against the high energy demands of the diabetic brain. The spare reserve capacity is a backup of extra ATP to be used in cases of sudden energy demands; a decrease in this function would lead to increased mitochondrial stress and damage to neurons. 

NMN improved mitochondrial respiratory function and upregulated sirtuin expression.

5. NMN Upregulated Sirtuin Expression  

Sirtuins are a family of proteins linked to increased longevity; their function depends on NAD+. One of the sirtuins, SIRT1, is highly expressed in the hippocampal neurons; low levels of SIRT1 are linked to cognitive decline. 

In this study, NMN supplementation enhanced levels of SIRT1 and the protein PGC-1α, both of which protect against neurodegeneration. NMN also activated levels of SIRT3 within the mitochondria and promoted deacetylation of proteins, which increases DNA repair and regulates cellular death and metabolism.  

In summary, this study produced highly encouraging results for the use of supplemental NMN with diabetes-related cognitive impairment. As the research was done only with rats, we do not yet know if results can be extrapolated to humans. 

NMN has been shown to be safe for human consumption; however, more research is still needed on whether or not NMN can be used as a therapeutic strategy for preventing or reversing cognitive decline. 

Key Takeaway

  • Diabetes increases the risk of cognitive impairment and Alzheimer’s disease. 
  • A recent study aimed to assess the effects of supplemental NMN on cognitive impairment in diabetic rats. 
  • NMN supplementation prevented cognitive decline, improved memory scores, increased neuronal volume and number, and improved mitochondrial respiration. 

Show references
 

Chandrasekaran K, Choi J, Arvas MI, et al. Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons. Int J Mol Sci. 2020;21(11):3756. Published 2020 May 26. doi:10.3390/ijms21113756

Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153-160. doi:10.1507/endocrj.EJ19-0313

Lee HJ, Seo HI, Cha HY, Yang YJ, Kwon SH, Yang SJ. Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects. Clin Nutr Res. 2018;7(4):229-240. doi:10.7762/cnr.2018.7.4.229

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