Vitamin B3

Vitamin B3, also known as niacin, is a water-soluble B vitamin essential for optimal bodily function. Playing a pivotal role in energy metabolism, niacin assists in converting the food we consume into usable energy. 

Beyond its energy-producing function, niacin contributes to maintaining healthy skin, nerves, and digestion, while also facilitating cell communication and aiding in DNA synthesis and repair. 

Unlike some nutrients, our bodies do not store niacin, emphasizing the importance of regular consumption through diet. Niacin-rich foods include meat, fish, nuts and seeds, and green vegetables. 

Testing for niacin levels, interpretation of results, and natural strategies to enhance niacin status offer valuable insights into promoting overall well-being. In this article, we delve into the multifaceted aspects of niacin, providing comprehensive information to aid in a better understanding of its importance and implications for health.

Overview of B Vitamin Family

The B vitamin family comprises a group of water-soluble vitamins that play critical roles in numerous physiological processes essential for human health. 

Comprising eight distinct vitamins, it includes riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12), these vitamins are intricately related and often function as coenzymes in various metabolic pathways. 

VItamin B12 is the only B vitamin that can be stored in the body, in the liver.  All other B vitamins are quickly excreted through the urine, therefore they require daily repletion.  

Individually, the B vitamins contribute to energy production, DNA synthesis, nervous system function, and red blood cell formation, among other vital functions. Collectively, the B vitamins are indispensable for maintaining overall health and well-being, underscoring their importance in supporting various physiological systems within the human body.

Niacin (Vitamin B3)

What is Niacin?  [3., 15., 16.]

Niacin, also known as vitamin B3, is a water-soluble B-complex vitamin essential for various metabolic functions in the body. 

It exists in two forms: nicotinic acid and nicotinamide, both of which serve as precursors for the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes play crucial roles in energy metabolism, DNA repair, and cell signaling pathways. 

NAD and NADP are synthesized throughout the body from nicotinic acid or nicotinamide. Tissue levels of NAD are regulated by hepatic control and hormonal influences, with hepatic NAD hydrolysis releasing nicotinamide for distribution to tissues lacking the ability to synthesize these coenzymes from tryptophan. 

In the liver, excess plasma nicotinamide can be converted to storage NAD (NAD not bound to enzymes), while tryptophan and nicotinic acid contribute to storage NAD. 

As NAD is degraded, the nicotinamide can be recycled back to NAD via nicotinamide ribonucleotide.  

Niacin requirements are met through dietary sources and conversion from dietary proteins containing tryptophan, with an estimated conversion ratio of 60 mg of tryptophan to 1 mg of niacin or niacin equivalents.

Niacin deficiency can lead to a condition known as pellagra, characterized by symptoms such as dermatitis, diarrhea, dementia, and death if left untreated. 

Conversely, excess niacin intake, particularly from supplements, can cause adverse effects such as flushing, itching, and liver damage. 

Dietary sources of niacin include meat, fish, poultry, nuts, seeds, and fortified grains.

Functions of Niacin: What Does Niacin Do in the Body?  [12., 16.]

• Acts as a vital component in coenzyme 1 (NAD) and coenzyme 2 (NADP) in oxidation-reduction reactions by accepting or donating hydrogen ions, crucial for cellular metabolism and energy production.
• Niacin is essential for many metabolic processes: glycolysis, pyruvate metabolism, protein, amino acid metabolism, pentose biosynthesis, glycerol metabolism, synthesis of high-energy phosphate bonds, and fatty acid metabolism
• Niacin reduces triglycerides and very-low-density lipoprotein (VLDL) synthesis while increasing high-density lipoprotein (HDL) levels
• Niacin inhibits lipolysis in adipose tissue and hepatic synthesis of VLDL, lowering liver triacylglycerol formation
• Niacin also decreases synthesis of apolipoprotein B-100 and hepatic VLDL, thereby reducing the concentration of low-density lipoprotein (LDL) particles
• Additionally, niacin impairs cholesterol biosynthesis and enhances reverse cholesterol transport, contributing to its overall lipid-modulating effects
• Decreases cardiovascular disease risk through anti-oxidative, anti-inflammatory actions, and by increasing serum adiponectin
• Niacin displays anti-aging properties: research suggests that niacin plays a crucial role in combating aging-related processes and pathologies by maintaining optimal levels of nicotinamide adenine dinucleotide (NAD) in cells. Adequate dietary niacin intake helps maintain intracellular NAD concentrations, preventing cellular aging and death by supporting cell division and growth. NAD-dependent enzymes like sirtuin proteins and poly(ADP-ribose) polymerase (PARP) play key roles in protecting the genome and repairing damaged DNA. Reduced NAD levels have been linked to increased cancer incidence and oxidative stress, while the lifespan-extending effects of caloric restriction, mediated by sirtuins, suggest niacin's potential in preventing premature aging and age-associated neurological disorders.  [3.]

Recommended Daily Allowance (RDA) of Niacin

The RDA for adult males is 16 mg/day, and 14 mg/day for females.  In pregnancy the RDA increases to 18 mg/day, and it is set at 17 mg/day in lactation.  [9.]  

Niacin needs may be increased above these levels in individuals with certain diseases and women pregnant with or breastfeeding more than one baby.   

Sources of Niacin  [15.]

Rich sources of niacin include animal-based foods such as poultry, beef, pork, and fish, particularly tuna and salmon. Plant-based sources include whole grains like brown rice, as well as legumes including peanuts, nuts and seeds including sunflower seeds. 

Niacin in grains appears to be only about 30% bioavailable, while niacin as NAD/NADP in meat is much more bioavailable.  [9.] 

Additionally, niacin can be obtained from fortified foods such as cereals and bread, which are often enriched with this essential vitamin. Incorporating a balanced diet that includes a variety of these foods ensures an adequate intake of niacin to support overall health and well-being.

Supplements containing niacin are also common, either as part of a B complex supplement or as an individual niacin supplement. 

Niacin Forms and Supplementation Indications

Niacin Supplement Forms

Niacin supplements are available in various forms, each with distinct properties and applications. 

Nicotinic acid, one of the most common forms, is known for its cholesterol-lowering effects but is often associated with flushing as a side effect. 

Niacinamide, another form, lacks the vasodilatory effects of nicotinic acid and is often preferred for individuals sensitive to flushing. 

NAD (nicotinamide adenine dinucleotide) represents a more bioavailable form of niacin, directly involved in cellular metabolism and energy production. 

Extended-release niacin is a formulation of niacin available in concentrations ranging from 125 to 1000 mg, utilized primarily in the treatment of hyperlipidemia due to its reduced risk of hepatotoxicity compared to regular niacin.

Each form of niacin supplement offers unique benefits and considerations, allowing for tailored approaches to supplementation based on individual needs and tolerances.

Indications for Niacin Supplementation  [16.]

Pellagra

Treatment for pellagra typically involves oral nicotinamide administration, with adults receiving 100 mg every 6 hours initially, followed by 50 mg every 8 to 12 hours until skin lesions heal. Severe cases may require higher doses, up to 1 g three to four times daily, initially administered parenterally. 

For children, doses range from 10 to 50 mg every 6 hours. 

Concurrent therapy with other B vitamins, magnesium, and zinc, along with a calorie-rich diet, is recommended. Topical emollients can alleviate discomfort from skin lesions. 

Hyperlipidemia

Sustained-release niacin formulations, available over-the-counter, offer a once-daily dosing option with reduced flushing but lack approval for hyperlipidemia due to potential hepatotoxicity. 

In dyslipidemia, niacin doses range from 1 to 6 g daily, with extended-release formulations preferred to minimize hepatotoxicity risks. Initial dosing starts low and increases weekly based on clinical response and tolerance.

Testing Options for Niacin Levels

Blood Tests

Blood tests are commonly used to measure niacin levels in the body. These tests typically involve drawing a blood sample from a vein, which is then analyzed in a laboratory to determine the concentration of niacin present. 

This test may assess levels of niacin or certain metabolites in plasma or red blood cells.

Plasma and red blood cell assessments tests for niacin status rely on specific metabolites to gauge adequacy. 

Plasma 2-pyridone, a derivative, diminishes with low niacin intake, particularly evident after oral nicotinamide load. This responsiveness surpasses other metabolites like N1-methyl-nicotinamide in plasma.  [9.]

However, niacin and other metabolite concentrations in plasma may not be reliable markers for niacin status, although these tests are commonly available.  [9.]

Alternatively, red blood cell NAD concentration serves as a sensitive indicator of niacin depletion. Studies have shown a substantial reduction in erythrocyte NAD, while NADP remains unchanged under low-niacin diets.  [6., 9.]

This measure offers a reliable marker akin to urine metabolite excretion, demonstrating its sensitivity across different age groups.

Urine Tests

Urinary excretion of N1-methyl-nicotinamide and its 2-pyridone derivative serves as the most reliable measure of niacin status. 

Criteria suggest that adults excreting less than 5.8 μmol/day of N1-methyl-nicotinamide indicate deficiency, while 5.8 to 17.5 μmol/day suggests low status.  [9.] 

The ratio of 2-pyridone to N1-methyl-nicotinamide shows associations with pellagra symptoms, particularly dermatitis, and may be a reliable marker of niacin status.  [2.]

Test Procedure and Preparation Guidelines

The procedure for testing niacin levels typically involves a blood draw.  Alternatively, urine samples may be collected at home or in a lab setting.  

Before undergoing niacin testing, individuals may be instructed to fast for a certain period and avoid consuming niacin-rich foods or supplements to prevent interference with the results.

It's essential to follow any preparation guidelines provided by the healthcare team to ensure accurate test results and to discuss any medications or supplements being taken that could affect niacin levels.

Interpretation of Niacin Testing

While individual labs may report different reference ranges, the reference ranges for niacin testing from one lab are:  [1.]

Serum or plasma: 

Nicotinic acid: 0.0−5.0 ng/mL

Nicotinamide: 5.2−72.1 ng/mL

Urine: often expressed as the ratio of 2-pyridone to N1-methyl-nicotinamide; contact lab for reference ranges used.

Erythrocyte: contact lab for reference ranges used.

Clinical Significance of High Niacin Levels

High niacin levels can lead to adverse effects.   There is no evidence of harm from excessive intake of niacin from food.  [9.]

While niacin is water-soluble and excess amounts are typically excreted through urine, extremely high doses, particularly from supplementation, can cause symptoms such as flushing, itching, and burning sensations, commonly referred to as niacin flush. 

Common symptoms of niacin excess include:  [9.] 

• Flushing: the most common adverse effect of excessive niacin intake is vasodilatory effects known as flushing, characterized by a burning, tingling, itching sensation, and reddened flush primarily on the face, arms, and chest.
• Nonspecific gastrointestinal effects: nausea and vomiting are also common in patients treated with nicotinic acid, especially with slow-release preparations.
• Liver damage: hepatotoxicity has been demonstrated in numerous case reports, with severe manifestations including liver dysfunction and fulminant hepatitis requiring liver transplantation, typically associated with high doses used to treat hypercholesterolemia for extended periods.
• Large doses of nicotinic acid have been associated with impaired glucose tolerance, and ocular effects such as blurred vision, toxic amblyopia, macular edema, and cystic maculopathy have been reported with doses ranging from 1.5 to 5 g/day of niacin.

Therefore, it's essential to consume niacin within the recommended dietary intake levels and avoid excessive supplementation to prevent these adverse effects.

Clinical Significance of Low Niacin Levels

Low niacin levels, or niacin deficiency, can have significant clinical implications, leading to a condition known as pellagra.

Pellagra is a condition characterized by the "4 Ds": diarrhea, dermatitis, dementia, and death. Dermatitis typically presents as erythema resembling sunburn, often seen on sun-exposed areas such as the neck, known as Casal necklace. 

Gastrointestinal symptoms associated with pellagra encompass diarrhea, nausea, vomiting, epigastric discomfort, poor appetite, abdominal pain, and increased salivation. 

Neurological manifestations include confusion, hallucinations, irritability, psychomotor unrest, ataxia, and depression, which may progress to confusion, coma, and ultimately death if left untreated.

Natural Ways to Optimize B Vitamin Status

Dietary Sources of B Vitamins

Incorporate a variety of foods rich in B vitamins such as:

• Whole grains like brown rice, oats, quinoa, and barley
• Leafy greens such as spinach, kale, and Swiss chard
• Legumes including lentils, chickpeas, and black beans
• Nuts and seeds like almonds, sunflower seeds, and flaxseeds
• Lean meats such as chicken, turkey, and beef
• Dairy products like milk, yogurt, and cheese
• Eggs, particularly the yolk which contains B vitamins
• Seafood such as salmon, tuna, and mackerel which are rich in B12
• Include fortified foods like fortified cereals, bread, and plant-based milk alternatives to increase B vitamin intake.

Lifestyle Strategies to Optimize B Vitamin Status

• Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to ensure adequate B vitamin intake.
• Avoid excessive alcohol consumption as it can interfere with the absorption and utilization of B vitamins, particularly B1 (thiamine), folate and vitamin B6.  [8.] 
• Manage stress levels through relaxation techniques such as deep breathing exercises, meditation, yoga, or mindfulness practices, as chronic stress can deplete B vitamin stores.  [20.] 
• Get regular physical activity, which can help improve overall metabolism and enhance the body's utilization of B vitamins.  Increasing exercise increases vitamin B needs, so supplementing may be desirable in some individuals.  [11.] 

Medications That Lower Vitamin B Levels in the Body

Individuals taking the following medications may want to discuss their B vitamin needs with their healthcare provider:

• Metformin: Used to treat type 2 diabetes, metformin can reduce vitamin B12 absorption and increase the risk of deficiency over time.  [10., 13.]
• Proton pump inhibitors (PPIs): These medications, such as omeprazole and esomeprazole, are commonly used to treat acid reflux and peptic ulcers. Long-term use of PPIs can interfere with the absorption of vitamin B12.  [7., 13.]
• Histamine H2-receptor antagonists: Drugs like ranitidine and cimetidine, used to reduce stomach acid production, may also impair vitamin B12 absorption.  [13.]
• Anticonvulsants: Some antiepileptic drugs like phenytoin, phenobarbital, and primidone can lower levels of folate and vitamin B12 in the body.  [17.] 
• Chemotherapy drugs: Chemotherapy medications can affect the body's ability to absorb and utilize B vitamins, leading to deficiencies.  [5.] 
• Oral contraceptives: Some birth control pills can deplete levels of B vitamins, particularly folate and vitamin B6.  [19.] 
• Diuretics: Certain diuretic medications, including loop and thiazide diuretics, can increase urinary excretion of B vitamins, particularly vitamin B1 (thiamine) and folate.  [14., 18.]

It's important to consult with a healthcare professional if you're taking any of these medications to discuss potential nutrient deficiencies and appropriate supplementation, if needed.

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