My fascination with niacin started in the 1980s when I was struggling with abdominal obesity and pre-diabetes. However, my research into it started with brain health and cognitive function in the 1990s. I found that niacin was vital in neuroprotection but also caused neuronal death in the central nervous system. As the brain and heart are related, I wondered about their role in cardiovascular health and investigated nuances.
Learning about pleiotropic hypolipidemic agents within the cardiometabolic health context was invaluable. Pleiotropic means that the agent has multiple effects on various physiological processes beyond its primary intended purpose. In other words, it is synergistic.
In the context of hypolipidemic agents, which are drugs used to lower lipid levels in the blood (such as cholesterol and triglycerides), pleiotropic effects include reducing LDL and increasing HDL cholesterol, lowering triglycerides, making anti-inflammatory and anti-oxidant effects, improving endothelial function, and stabilizing plaques.
Examples of medications with pleiotropic effects include statins, fibrates, and niacin, which I will cover in this story. Even though vitamin B3 is an essential nutrient and we all need to get it from food, in this post, I mainly focus on its therapeutic effects, which are less known by the public.
My First Real-Life Encounter and Experimentation with Niacin
In my youth in the mid-1970s, when I was on a strict plant-based diet, I faithfully consumed a multivitamin tablet. However, it was pivotal when my friends in the nutrition community urged me to prioritize full-spectrum B vitamins, emphasizing their crucial role in supporting my dietary needs.
Among the vitamins in that costly blend, Vitamin B3 stood out. As they said, it did boost my energy and helped reduce stress during my busy student days. But eventually, its effects wore off.
In the early 1980s, when I was having metabolic nightmares, a compassionate young family doctor who was into holistic health noticed my discomfort in a miserable situation and suggested blood tests.
To her surprise, my lipid profiles were irregular, even though I avoided fatty foods due to fear of fat. My cholesterol levels, particularly LDL, were elevated. When she informed me about my elevated triglyceride levels, which could be contributing to my abdominal obesity, I was stunned because I did not consume any fats.
Back then, I didn’t understand the intricacies of fat and sugar metabolism. During our heartfelt conversation, she explained that the surplus carbs I consumed for energy were converting into fat molecules due to the lack of healthy fats in my diet for energy.
She wanted to start me on a 500 mg dose of niacin while checking my sugar levels and advising me to eat healthy fats from avocadoes and nuts as I did not want to consume animal products like meat, cheese, and butter.
When I mentioned that I already took a vitamin combo containing B3, she explained that it was a different form called nicotinamide. She prescribed it and cautioned me that niacin might cause discomfort initially.
I thought it would be a simple side effect like many other supplements I used back then. But this one hit me so hard that I thought I was poisoned. After 20 minutes, my entire body turned red, and I experienced what she called flushes. My face, neck, hands, and feet felt intensely itchy and uncomfortable.
Since there were no home or mobile phones back then, I couldn’t ask for help. I tried to soothe the itchiness and redness with an ice pack. The good news is that after an hour, all symptoms disappeared, and I started feeling very pleasant. That night, I slept like a baby, which was a relief as I used to suffer from insomnia.
I stopped taking it until I saw my doctor again. She confirmed that my body would get used to it and that I should find ways to tolerate it. She was right. As day by day, the symptoms lessened and became bearable. After a few months, my lipid profile improved significantly, and my energy levels increased.
Several years later, I tried niacin again for its other benefits, and my body reacted harshly once more. However, this time, I utilized my mindfulness skills to observe the flush and used it as an anchor. Surprisingly, it gave me extra pleasure while enabling me to tolerate the side effects.
Why does niacin cause flushes, and is it a good or bad indication?
In those years, my doctor assured me that flushing was not harmful to the body and was just a temporary nuisance, but she did not explain the reasons to me. So, it stayed on my backburner as a curiosity item until I systematically started researching niacin for cognitive function and mental health.
During my research, I investigated the mechanisms. It was actually a hormonal factor and biochemical reaction. So, the flushing reaction occurs due to niacin’s ability to cause blood vessel dilation (vasodilation) near the skin’s surface, leading to increased blood flow and a sensation of warmth and redness.
From a hormonal aspect, I found that niacin stimulates the release of prostaglandins, particularly prostaglandin D2 (PGD2), from cells called Langerhans cells in the skin. PGD2 causes blood vessels to dilate, leading to increased blood flow and the characteristic flushing response.
The second factor is the activation of niacin receptors. Niacin binds to GPR109A receptors. When activated, these receptors trigger a cascade of events, resulting in vasodilation and flushing.
In addition, niacin can stimulate the release of histamine, a molecule involved in allergic reactions and inflammation. Histamine causes blood vessels to dilate and contributes to the flushing response. I introduce histamine as a neurotransmitter in a previous article titled Histamine: The Many Hats of a Paradoxical Biochemical for the Body and Mind.
Therefore, the flushing reaction caused by niacin is generally considered a side effect rather than a therapeutic effect. However, while the flushing can be uncomfortable, it is usually harmless and temporary.
In fact, some researchers believe that niacin-induced flushing may have cardiovascular benefits, as it is associated with improved lipid profiles and reduced risk of cardiovascular events, as I will cover in the next section.
Insights from the Literature: Why is niacin so popular in health communities?
In this part, I will walk you through memory lane by highlighting a few remarkable papers out of about 15,000 medical or scientific reports in English found in Pubmed. This will give you a glimpse into the history of niacin.
In 1959, when I was a child, psychiatrist Dr Abraham Hoffer (MD, PhD) published an outstanding clinical paper that you may find in the medical archives of Pubmed Central.
I met Dr Hoffer (RIP) at a conference in 1999 when he was 82 years old and working as a volunteer consultant supporting young scientists. He was friendly, humble, and articulate. Yet, he was heartbroken as many young scientists ignored his remarkable findings.
After a comprehensive literature review on its use for mental health conditions like schizophrenia, he delved into its therapeutic effects on arthritis in the paper. Interestingly, as he advised me, he wrote the paper in a very easy language compared to the scientific papers of the 2000s.
Apart from arthritis, Dr. Hoffer also investigated niacin’s effects on neurodegenerative diseases (Alzheimer’s, Parkinson's, Huntington's, ALS), muscular atrophy, hyperphosphatemia in chronic kidney disease, schizophrenia, circadian rhythm regulation, intracellular calcium regulation, diabetic encephalopathy, and Squamous cell carcinoma as mentioned in an NIH book chapter. Unfortunately, his research, including 500 papers, was buried in archives.
Fast forward to the 2000s, a 2008 Mayo Clinic Proceeding informed that niacin, a medication that increases good cholesterol and lowers triglycerides, may help reduce cardiovascular risk in patients with diabetes or mixed dyslipidemia, especially when combined with statins.
The paper also mentioned that studies reviewed from 1990 to 2007 showed that niacin, alone or with statins, had modest and reversible effects on blood sugar levels, with minimal risk of causing diabetes or requiring insulin. Despite these effects, niacin therapy still provided significant benefits in preventing heart-related events and slowing artery blockage.
Researchers recommended monitoring blood sugar levels when starting or increasing niacin dosage, but the benefits outweigh the mild impact on blood sugar control overall.
Then, in 2011, another outstanding paper in the International Journal of Practice titled Niacin: “the only vitamin that reduces cardiovascular events” mentioned that in clinical trials involving patients with diabetes mellitus or mixed dyslipidemia, niacin has shown promising results in counteracting cardiovascular risk. When used in conjunction with statin drugs, niacin has been observed to reduce cardiovascular morbidity and mortality within this patient population.
The same year, another excellent paper in Current Vascular Pharmacology informed that niacin is effective in improving cholesterol levels and reducing the risk of cardiovascular disease by preventing blood clots, reducing inflammation, and fighting against oxidative stress.
So they mentioned that a new version of niacin combined with a prostaglandin D2 receptor antagonist called laropiprant seems to significantly reduce flushing without affecting niacin’s other benefits. However, there are some concerns about niacin affecting glucose metabolism and raising uric acid and homocysteine levels.
The paper concluded that niacin is a safe supplementary (to statins) lipid-lowering agent, which may also improve cardiovascular outcomes. Whether its combination with laropiprant will be proved equally effective and more favorable regarding adverse effects remains to be established by extensive clinical trials.
Summary of 4 Well-Documented Functions of Niacin in the Body
As niacin is highly complex and has many functions, I will summarize the key points from an NIH book to make it easy for you to understand.
After undergoing biochemical reactions in the mitochondria with nicotinamide and tryptophan, niacin forms nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), they participate in catabolic redox reactions and are cofactors in anabolic redox reactions.
Simply, they break down substances in our cells and build new ones. They act like helpers or assistants in these chemical processes. Here is a summary of the known key functions of niacin in the body.
1 — Lipid metabolism: Niacin can lower LDL (bad cholesterol) levels and raise HDL (good cholesterol) levels. It does this by slowing down the breakdown of fats and inhibiting the production of triglycerides.
2 — Increased blood sugar levels: Niacin might raise blood sugar levels, which could concern people with diabetes or those at risk for it.
3 — Aging and diseases: Niacin seems to be connected to how cells age and repair themselves. Low levels of NAD may contribute to cell aging and diseases.
4 — Malignant glioma: Niacin might help stop the spread of cancer cells in the brain, particularly in a type of brain tumor called glioma. It seems to affect specific processes in the cells that are involved in their ability to invade other tissues.
The Effects of Niacin on the Brain and Nervous System
Understanding the intricate mechanisms underlying niacin’s effects on neuronal health is essential for developing therapeutic strategies to preserve nervous system function and mitigate neurodegenerative diseases.
Niacin is like a double-edged sword in the brain. It is critical for the proper functioning of the central nervous system. It plays a significant role in neuroprotection and neuronal death processes. So, we need to understand their nuances.
As documented in this paper, these two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair, and cell death. Niacin has long been recognized as a critical mediator of neuronal development and survival in the central nervous system.
In the context of neuroprotection, niacin has been studied for its potential to mitigate oxidative stress and inflammation, which are key factors in the pathogenesis of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. In this context, I introduced NADH in a previous article.
Niacin’s antioxidant properties help scavenge free radicals and reduce oxidative damage to neurons, thereby promoting their survival and overall nervous system health.
Conversely, niacin also has implications for neuronal death processes. Niacin metabolism may contribute to neuronal death pathways in specific contexts, such as during excitotoxicity or prolonged ischemia.
Excessive activation of certain niacin-dependent enzymes or dysregulation of niacin metabolism can lead to cellular stress and apoptosis, ultimately resulting in neuronal death.
While niacin is crucial for maintaining CNS function and protecting neurons from damage, dysregulation of its metabolism or excessive oxidative stress can contribute to neuronal dysfunction and cell death.
Besides, as explained in this PNAS paper, NAD has also been recognized as an endogenous agonist of purinergic P2Y1 and P2Y11 membrane subtype receptors, through which it inhibits neurotransmission in visceral smooth muscles and activates immune cells, respectively. Let me explain.
In simple terms, in visceral smooth muscles (the muscles in organs like the intestines), NAD reduces or inhibits the transmission of signals between nerve cells, which helps to relax these muscles and regulate their activity.
In immune cells, such as certain types of white blood cells, NAD activates them, triggering responses that are part of the body’s immune defense system. This activation helps immune cells perform their functions more effectively in response to infections or other challenges.
Potential Side Effects That Require Monitoring When Used as a Supplement or Medication
As documented in this NIH book, in pharmacological doses from 1000 to 3000 mg/day, a flushing reaction associated with its crystalline nicotinic acid is the most common toxicity of niacin. Other symptoms of toxicity may include dizziness, upset stomach, redness, itching, nausea, and vomiting.
Besides redness and flushes, regular blood glucose checks are necessary for those with pre-diabetes or diabetes because niacin can increase fasting blood sugar levels. Patients on diabetic medications should also monitor their blood glucose closely.
Additionally, niacin may lead to hyperglycemia when combined with certain medications and monitoring phosphorus levels is recommended due to potential decreases caused by niacin.
Niacin can also raise uric acid levels, affecting medications for gout, and interact with blood pressure drugs, opioids, antipsychotics, and other medications, potentially causing low blood pressure. It can also increase bleeding risk when combined with anticoagulants.
How About the use of Niacin for General Population
As documented by NIH, intake recommendations for niacin and other nutrients are provided in the Dietary Reference Intakes developed by an expert committee of the Food and Nutrition Board at the National Academies of Sciences, Engineering, and Medicine. As shown in the following table, we don’t need too much of it if we don’t have underlying health conditions.
My journey with niacin shows its critical and synergistic role in brain and heart health. Since its introduction as a therapeutic agent in the 1950s, after Dr Conrad Arnold Elvehjem found it in 1937, niacin has been at the forefront of holistic health discussions due to its multifaceted benefits.
Niacin’s pleiotropic hypolipidemic properties offer a holistic approach to managing lipid levels and mitigating cardiovascular risk, making it a cornerstone of preventive care and therapeutic intervention.
Niacin’s involvement in synthesizing NAD and NADP underscores its fundamental contribution to cellular metabolism and neuronal function, offering insights into its therapeutic potential in neurodegenerative diseases.
Using niacin in a holistic approach to health for therapeutic purposes requires understanding its pleiotropic hypolipidemic properties and physiological mechanisms.
Monitoring for potential side effects, such as flushing reactions, changes in blood glucose levels, and interactions with blood pressure drugs, opioids, and antipsychotics, is essential for patients considering niacin supplementation and medication.
Recognizing niacin’s complex interactions with medications and metabolic pathways highlights the importance of informed decision-making and personalized care.
While niacin offers promising benefits for brain and heart health, its medical or supplementary use should be cautiously approached, carefully considering individual health status and risk factors supported by qualified healthcare professionals.
Niacin’s role in neuroprotection and neuronal function highlights its therapeutic potential in neurodegenerative diseases and cognitive health. Therefore, healthy people must consume around 15 mg daily by eating whole foods to prevent deficiency.
Thank you for reading my perspectives. I wish you a healthy and happy life.
I also wrote about other molecules and nutrients like Digestive Enzymes, Boron, Urolithin, taurine, citrulline malate, biotin, lithium orotate, alpha-lipoic acid, n-acetyl-cysteine, acetyl-l-carnitine, CoQ10, PQQ, NADH, TMG, creatine, choline, digestive enzymes, magnesium, zinc, hydrolyzed collagen, nootropics, pure nicotine, activated charcoal, Vitamin B12, Vitamin B1, Vitamin D, Vitamin K2, Omega-3 Fatty Acids, N-Acetyl L-Tyrosine, and other nutrients to improve metabolism and mental health. You might find search them through Google or other search engines. They reflect my experience, observations, and literature reviews.
One of my writing goals is to raise awareness about the causes and risk factors of prevalent diseases that can lead to suffering and death for a large portion of the population. I aim to educate, create awareness, and empower my readers to take control of their health and well-being.
To raise awareness about health issues, I have written several articles that present my holistic health findings from research, personal observations, and unique experiences.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.
To inform my new readers, I wrote multiple articles that might inform and inspire you. My topics include brain and cognitive function, significant health conditions, longevity, nutrition/food, valuable nutrients, ketogenic lifestyle, self-healing, weight management, science, technology, business, and humor.
Thanks for the helpful article on niacin which is very good for balancing my lipids after my 70s. I take an aspiring with it and it does not cause flushing with it.
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