SPOTLIGHT ON VITAMIN B3 FOR THE CNS EXAM WITH CAITLIN SELF

B-vitamins are a challenging concept to master for the CNS Exam. We consider them a family because they share similar functions and work together in various metabolic pathways. 

But, as a result, they also share a lot of characteristics that make them challenging to differentiate from each other when you’re studying for the CNS exam or answering questions on exam day!

We’ll take a look at some of their shared characteristics, and then we’ll put the Spotlight on B3! Hopefully this spotlight will capture everything you may need to know about this vitamin for the CNS test. 

B Vitamins: 

Here are some of their shared characteristics: 

• They’re all vitamins - meaning we have to consume them from food or supplements!

• They’re all water soluble. No fat needed for absorption or elimination. 

• They’re all cofactors for enzymes involved in different metabolic pathways. Their structures vary, but they all play a role in converting calories into energy. 

• Many, but not all, share similar deficiency symptoms

  • B1, B2, B3, B5, B6, B7 all share similar skin-related functions and symptoms 

  • B9 and B12 share similar deficiency symptoms, with B3 and B6 used in some of the same pathways - these B vitamins all have metabolic connections 

The B vitamins and their names: 

1. Thiamine (B1)

2. Riboflavin (B2)

3. Niacin (B3)

4. Pantothenic Acid (B5)

5. Pyridoxine (B6)

6. Biotin (B7): Plays a role in energy, fat, and amino acid metabolism.*

   1. Note that Biotin isn’t always classified as a B vitamin across all sources, but it is considered an essential nutrient. The NIH classifies it as a B vitamin. 

7. Folate (B9)

8. Cobalamin (B12)

All about Vitamin B3

• Aka niacin

• Aka niacinamide

• Aka nicotinic acid 

Yep, this B vitamin has a lot of names - it’s so extra. Niacin is the public name that was given to nicotinic acid (the chemical name) so as not to confuse it with nicotine. 

Here are some fast facts: 

• By definition, a vitamin MUST be an essential nutrient, and CANNOT be synthesized by the human body. And by this definition, B3 is technically not a vitamin. Do you know what it can be synthesized from in the human body? The amino acid Tryptophan!

• A severe niacin deficiency can cause a disease called Pellagra, which has 4 major defining characteristics (The 4 D’s of Pellagra): dermatitis, diarrhea, dementia, and death. 

• The government mandated enrichment and fortification programs involving niacin in 1942, and in 1943, all corn, wheat, and rice flours were required to be enriched to treat widespread deficiencies. 

• Niacin primarily functions in metabolic pathways like glycolysis and in redox reactions as NAD, NADH, and NADP. (Whenever you see NAD - know that B3 is involved!) 

• Higher supplement doses are used as a cholesterol lowering treatment, but these forms cause flushing. Non-flushing types do not treat cholesterol.  

Energy Metabolism

Much like other B-vitamins, Niacin is involved in many energy metabolism pathways. One of the primary roles niacin plays is as NAD. 

• MEMORIZE: NAD+/NADH are central to the breakdown of food into usable energy. (Glycolysis, for example) 

• MEMORIZE: NADPH, the reduced form of NADP+, is crucial for building complex molecules (Fatty Acid Synthesis, for example) 

• MEMORIZE: B3 and its coenzymes also power critical cellular processes beyond simple metabolism. (DNA repair and calcium homeostasis, for example) 

Tryptophan to Niacin 

The kynurenine pathway is the main metabolic route for the essential amino acid tryptophan, which then produces nicotinamide adenine dinucleotide (NAD+).* 

Kynurenine pathway:

Tryptophan → kynurenine → quinolinic acid → nicotinic acid mononucleotide → NAD 

MEMORIZE: 

• 60 mg of Tryptophan yields 1 mg Niacin. 

• Riboflavin (vitamin B2), Pantothenic acid (vitamin B6), and iron are required for this conversion

• The conversion takes place in the liver 

*Reminder that Tryptophan can alternatively be converted to serotonin and then melatonin through another pathway. 

Deficiency Disease: Pellagra (Dermatitis, Diarrhea, Dementia, and Death)

This condition was first identified in Spain and Italy, and reached epidemic proportions in the American South in the early 1900’s, mostly in the more impoverished communities consuming high intakes of corn products. For some time it was believed to be an infectious disease, but around 1914, a clinician named Dr. Joseph Goldberger observed cases in southern orphanages and prisons and discovered it was a deficiency disease. 

Symptoms often started in the spring and summer: 

• Dermatitis was more sensitive to the sun’s rays, and these symptoms would show up and worsen with sun exposure 

• A winter diet high in corn and low in meat, milk, and fresh vegetables would catch up with people in the spring and summer 

  • Here’s why the disease was linked to a corn-rich diet: there is niacin present in corn, but it is only bioavailable in nixtamalized corn. European colonizers, and the Africans they enslaved, did not have the thousands of years of food traditions and knowledge that the Natives in the Americas had. Non-native populations were not always using nixtamalized corn. 

Food sources of Niacin: 

The US Government made it mandatory to fortify and/or enrich certain foods (wheat flour and cereal products) with B vitamins (and iron) in the 1940s to combat widespread deficiencies. Niacin, thiamine, riboflavin were all part of this plan. 

Food sources of niacin/B3: chicken, liver, fish (tuna, salmon), whole grains, legumes, dairy, also crimini mushrooms, asparagus, whole wheat, PLUS enriched grain and flour products, including white bread and breakfast cereals 

Food sources of tryptophan (a precursor to B3): seafood (shrimp, cod, tuna, scallops), poultry (chicken, turkey), liver, red meat, also crimini mushrooms, spinach, tofu

Supplementation:

Niacin supplements, especially at higher doses, can cause vasodilation, which is why they are used for high cholesterol. However, this vasodilation causes skin flushing, which can be extreme and sometimes uncomfortable, and can feel like burning or itchy skin. I have seen a client take a high dose of niacin and turn bright red within 30 minutes. 

This use would be as a nutraceutical rather than as a treatment for a deficiency. Flushing is usually associated with 1000mg doses and higher, but has been observed in doses as low as 30mg. 

“Consumption of more than 30 mg of niacin may cause cutaneous vasodilation and flushing. Skin flushing is caused by the dilatation of tiny subcutaneous blood vessels, which, while typically benign, can occasionally cause sensations of burning, tingling, and itching, resulting in unpleasant responses ” (Source)

Supplement Forms: 

• Nicotinamide - Most Common Form

  • Usually used in food fortification 

  • Main treatment for pellagra

  • Generally low liver toxicity and no flushing

• Inositol Hexanicotinate - “Flush-Free Niacin”

  • No effects on cholesterol

  • 2-4 g/day = no liver toxicity

• Nicotinic acid (OTC & Prescription available) 

  • Prescribed for cholesterol-lowering effects

  • Causes flushing

Deficiency Symptoms: 

• Early Signs: nervousness, headaches, forgetfulness, functional GI disturbances

• Severe Deficiency: weakness, muscle weakness, lack of appetite, dermatitis (and skin photosensitivity), rough lesions and skin patches, diarrhea, dementia, death  

Sample of CNS Test Questions: 

1) A client has the following symptoms: anxiety, dermatitis, and mental confusion. A deficiency of which of the following is most likely responsible for her symptoms?

1. Thiamin (B1)

2. Riboflavin (B2)

3. Niacin (B3)

4. Pantothenic acid (B5) 

2) Which of the following is true regarding Niacin / B3?

1. The supplemental form inositol hexanicotinate of B3 is often prescribed for lowering cholesterol.

2. 1mg of niacin can be synthesized from 60mg of tryptophan 

3. Pellagra is defined by the 4D’s: diarrhea, dermatitis, dehydration, and death 

4. It is a crucial component of Coenzyme A 

3) Which of the following is a precursor to niacin?

1. Tyramine

2. Tyrosine

3. Threonine

4. Tryptophan 

ANSWERS BELOW!

Answers to Example Questions: 

1. Answer: C. Niacin (B3)

2. Answer: B. 1mg of niacin can be synthesized from 60mg of tryptophan 

3. Answer: D. Tryptophan 

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