Niacin adequacy is protective in part by increasing BDNF

*This topic came up in a copyrighted webinar, so here is a brief AI supported summary. I'm on a time limit to finish a course from last summer :-) Aug 6....

BDNF is protective of the brain and has been found to be reduced in Alzheimer’s dementia. Exercise is a way to promote more BDNF and niacin seems to help too, possibly by microRNA regulation of its production. (miR-206 regulates brain-derived neurotrophic factor in Alzheimer ..., 2013).

While higher dose niacin or niacinamide can be bad for the liver, and elevate uric acid levels which can cause gout pain and is inflammatory to general health, having an adequate to generous amount of niacin likely can help with energy level, thinking clarity, and weight control. It can help with serotonin levels which can help prevent depression and anxiety. Niacinamide doesn’t do as much towards reducing inflammation as niacin.

Niacin functions also require vitamins B2 and B6, and iron for an enzyme. Niacin and serotonin and melatonin can be made from the amino acid precursor tryptophan but it would be slow - we need more niacin than our bodies can make from tryptophan alone. Taking niacin helps preserve tryptophan for it to be made into serotonin and melatonin and the niacin can be converted too.

“Humans obtain niacin from both endogenous and exogenous sources. Only 2% of dietary tryptophan (Trp) is converted into niacin via a multistep pathway (see in next sections), occurring mainly in the liver [10]. Diet provides the vitamin as nicotinic acid, nicotinamide and Trp, as well as the active coenzymatic forms of niacin” (Gasperi, et al., 2019)

Niacin is the ‘flush’ type, causing reddening and clearing of the nose due to TRPV channel activation, similarly to capsaicin - from eating hot pepper. Niacinamide is most commonly available now in multi-vitamin supplements because it doesn’t cause the flushing reaction, but it may not do as much for us because it is a less bioactive form - it is a step or two farther along the niacin metabolic pathways.

Figure 1 Chemical structures of niacin vitamers (A) and active coenzymatic forms (B). NAD: nicotinamide adenin dinucleotide. NADP: nicotinamide adenin dinucleotide phosphate. (Gasperi, et al., 2019)

“Niacin (also known as “vitamin B₃” or “vitamin PP”) is the generic descriptor for two vitamers, nicotinic acid (pyridine-3-carboxylic acid) and nicotinamide (nicotinic acid amide), that give rise to the biologically active coenzymes, nicotinamide adenine dinucleotide (NAD) and its phosphate analog, the nicotinamide adenine dinucleotide phosphate (NADP) [1] (Figure 1). The two coenzymes take part in redox reactions crucial for energy production: in particular, the pyridinic ring can accept and donate a hydride ion (:H⁻, the equivalent of a proton and two electrons), thus acting as an electron carrier. Nonetheless, NAD and NADP play different metabolic roles in the cytosol: the NADH/NAD⁺ ratio is small (about 8 × 10⁻⁴), thus favoring oxidative catabolism, whereas the NADPH/NADP⁺ ratio is higher (about 75), thus providing a strongly reducing environment for biosynthetic reactions [2,3].” (Gasperi, et al., 2019)

Niacin is too helpful and important to be ‘canceled’ by the recent study that suggested large doses may increase heart disease risk. Deficiency of niacin is known as pellagra can cause the “4 D’s”, in progressive order - diarrhea, dermatitis, dementia, death. (Brave Summary) The skin problems can be characteristically seen as a reddened tongue, but may also be present on the lower legs along with puffy swelling possibly. Characteristically enough, that if you see bad lower leg health, consider trialing niacin just in case.

Niacin’s regulatory control over the brain-protective BDNF may help explain why dementia is one of the classic symptoms of niacin deficiency.

We need to be protecting our brains in this stressful and toxin filled modern world.

Niacin and BDNF

Niacin, also known as vitamin B3 or nicotinic acid, has been found to have a positive impact on Brain-Derived Neurotrophic Factor (BDNF) levels. BDNF is a protein that plays a crucial role in the growth, survival, and differentiation of neurons, and its levels have been linked to various neurological and psychiatric conditions, including depression, anxiety, and Alzheimer’s disease.

Studies and Findings

1. Stroke Recovery: A study published in the Journal of Cerebral Blood Flow & Metabolism found that niacin treatment increased synaptic plasticity and axon growth in rats after stroke, which was associated with elevated BDNF levels (Cui et al., 2009). “Niacin treatment of stroke promotes synaptic plasticity and axon growth, which is mediated, at least partially, by the BDNF/TrkB pathways.” (Cui, et al., 2010)

2. Neurite Outgrowth: In vitro studies have shown that niacin and high-density lipoprotein (HDL) enhance neurite outgrowth and BDNF expression in primary cultured neurons (Cui et al., 2009). “Niacin and HDL treatment significantly increased neurite outgrowth, and BDNF/TrkB expression in PCNs. TrkB-inhibitor attenuated Niacin-induced neurite outgrowth (p<0.05, n=6/group).” *Animal-based study. (Cui, et al., 2010)

3. Alzheimer’s Disease: Research suggests that niacin may help regulate BDNF levels in Alzheimer’s disease, potentially contributing to its therapeutic effects (miR-206 regulates brain-derived neurotrophic factor in Alzheimer ..., 2013).

4. Increased BDNF Expression: A study published in the Journal of Neurochemistry found that niacin treatment increased BDNF expression in the ischemic brain of rats (Zhang et al., 2018).[?] “Thus, niacin improves endothelial tube formation under lipotoxic and hypoxic conditions, and moreover, promotes revascularization and functional hind limb recovery following ischemic injury in diet‐induced obese mice with hyperlipidemia. These data may have implications for niacin therapy in the treatment of peripheral ischemic vascular disease associated with metabolic syndrome.” (Pang, et al., 2016)

Mechanisms and Implications

The exact mechanisms by which niacin influences BDNF levels are not fully understood, but potential pathways include:

1. Mitochondrial energy production: Niacin’s ability to improve mitochondrial energy production may contribute to its effects on BDNF expression (Vitamin B3 (Niacin) - Nootropics Expert, 2024).

2. Inhibition of miR-206: Niacin may inhibit the activity of miR-206, a microRNA that regulates BDNF expression, thereby increasing BDNF levels (miR-206 regulates brain-derived neurotrophic factor in Alzheimer ..., 2013).

Overall, the available evidence suggests that niacin may have a positive impact on BDNF levels, which could have therapeutic implications for various neurological and psychiatric conditions. However, further research is needed to fully elucidate the mechanisms and potential clinical applications of niacin’s effects on BDNF.

BDNF in dementia

Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis

• Studies consistently show lower BDNF levels in patients with AD compared to healthy controls.

• A meta-analysis of 15 studies found a significant decrease in serum BDNF levels in AD patients (SMD = -1.23, 95% CI = -1.55 to -0.91).

• The decrease in BDNF levels was more pronounced in patients with moderate to severe AD compared to those with mild AD.

Prospective Association between Serum BDNF Levels and Risk of Dementia

• A 10-year prospective study in the Framingham Heart Study found that higher serum BDNF levels were associated with a reduced risk of dementia and Alzheimer’s disease (HR = 0.67, 95% CI = 0.53-0.84).

• The association was stronger in women, older adults (≥80 years), and those with higher education.

Brain-Derived Neurotrophic Factor and Tau-Related Neurodegeneration

• BDNF has been shown to protect against tau-related neurodegeneration in Alzheimer’s disease.

• Gene delivery of BDNF using adeno-associated virus (AAV-BDNF) was well-tolerated and reduced tau pathology in mouse models of Alzheimer’s disease.

Other Studies

• A study in community-dwelling older adults found that lower BDNF levels were associated with age-related memory impairment.

• Another study reported decreased serum BDNF levels in elderly Koreans with dementia.

Conclusion

• Decreased serum BDNF levels are consistently observed in patients with Alzheimer’s disease.

• Higher BDNF levels may protect against the risk of dementia and Alzheimer’s disease, particularly in women, older adults, and those with higher education.

• BDNF may have therapeutic potential in the treatment of Alzheimer’s disease and other neurodegenerative disorders.

Note: The above summary is based on the provided search results and does not include all possible studies or perspectives on the topic.

Context for BDNF in Dementia

1. www.ncbi.nlm.nih.gov, Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study

2. translationalneurodegeneration.biomedcentral.com, Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential | Translational Neurodegeneration | Full Text

3. www.ncbi.nlm.nih.gov, Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis - PMC

4. www.nature.com, Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: the Sefuri study | Scientific Reports

5. www.nature.com, Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease | Translational Psychiatry

6. www.frontiersin.org, Frontiers | Brain-Derived Neurot

Context for Niacin and BDNF and other References I added

1. www.hindawi.com, Nicotinamide Administration Improves Remyelination after Stroke Wang, Congxiao, Zhang, Yi, Ding, Jie, Zhao, Zhen, Qian, Cheng, Luan, Ying, Teng, Gao-Jun, Nicotinamide Administration Improves Remyelination after Stroke, Neural Plasticity, 2017, 7019803, 12 pages, 2017. https://doi.org/10.1155/2017/7019803

2. www.optimallivingdynamics.com, 31 Proven Ways to Increase BDNF, Your Brain's Growth Hormone — Optimal Living Dynamics

3. nootropicsexpert.com, Vitamin B3 (Niacin) - Nootropics Expert

4. selfhacked.com, All About BDNF + Natural Factors that Increase It - SelfHacked

5. www.ncbi.nlm.nih.gov, miR-206 regulates brain-derived neurotrophic factor in Alzheimer ... Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, Park DK, Lim JY, Kim JM, Jeon D, Ryu H, Lee SK, Kim M, Roh JK. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol. 2012 Aug;72(2):269-77. doi: 10.1002/ana.23588. PMID: 22926857.

6. www.wellnessresources.com, Niacin Boosts BDNF Production

7. Cui X, Chopp M, Zacharek A, Roberts C, Buller B, Ion M, Chen J. Niacin treatment of stroke increases synaptic plasticity and axon growth in rats. Stroke. 2010 Sep;41(9):2044-9. doi: 10.1161/STROKEAHA.110.589333. Epub 2010 Jul 29. PMID: 20671245; PMCID: PMC2932778. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932778/

8. Pang DK, Nong Z, Sutherland BG, Sawyez CG, Robson DL, Toma J, Pickering JG, Borradaile NM. Niacin promotes revascularization and recovery of limb function in diet-induced obese mice with peripheral ischemia. Pharmacol Res Perspect. 2016 Apr 14;4(3):e00233. doi: 10.1002/prp2.233. PMID: 27433343; PMCID: PMC4876143. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876143/ (Pang, et al., 2016)

9. Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int J Mol Sci. 2019 Feb 23;20(4):974. doi: 10.3390/ijms20040974. PMID: 30813414; PMCID: PMC6412771. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/ (Gasperi, et al., 2019)

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