Nicotinamid: Vitamin B3 in Therapy and Prevention

Nicotinamid, also called niacinamide, is one of two physiologically active forms of vitamin B3, the other being nicotinic acid (niacin). Both are converted in the body to the coenzyme nicotinamide adenine dinucleotide (NAD and NADP), which serves as a hydrogen carrier in countless metabolic processes. Nicotinamid is widely distributed in food, especially in meat, fish, eggs, whole grain products and nuts. It is available as a medicine and dietary supplement (for example in a vitamin B complex preparation or as a single substance Nicobion 200 as well as generic versions).

Nicotinamid has growing importance in dermatology and oncology. In dermatology, topical application of niacinamide in creams reduces pigmentation disorders, acne and sebum production. In oncology, the Australian ONTRAC study showed that oral nicotinamid 500 mg twice daily can significantly reduce the frequency of non-melanocytic skin tumors in high-risk patients. Nicotinamid has a favorable safety profile and differs pharmacologically significantly from nicotinic acid.

Mechanism of Action

Nicotinamid is synthesized in the body to NAD and NADP. These coenzymes are essential for cellular energy production in the citric acid cycle, in the respiratory chain and for more than 400 enzymatic reactions. Unlike nicotinic acid, nicotinamid does not activate the GPR109A receptor on adipocytes and therefore does not cause flushing. The lipid-lowering effect of nicotinic acid in hypercholesterolemia is also largely absent with nicotinamid.

NAD is a substrate of DNA repair enzymes such as PARP (poly ADP ribose polymerase) and of sirtuins, which intervene in cellular stress responses and gene expression. Nicotinamid can improve DNA repair after UV-induced skin damage and can reduce UV-induced immunosuppression. These mechanisms are likely responsible for the reduction of new squamous cell carcinomas and basal cell carcinomas in at-risk patients.

In the skin, nicotinamid also topically inhibits the transfer of melanosomes, which can reduce hyperpigmentation such as melasma. In acne, it has anti-inflammatory effects through modulation of cytokines and sebum regulation. Oral bioavailability is high, the half-life is a few hours, and dividing the daily dose into two individual doses is common.

Areas of Application

• Pellagra, classic vitamin B3 deficiency disease with dermatitis, diarrhea and dementia
• Vitamin B3 deficiency in malnutrition, chronic alcohol consumption, malabsorption syndromes
• Prevention of non-melanocytic skin tumors in high-risk patients according to ONTRAC study, orally 500 mg twice daily
• Topical use in dermatology for acne, hyperpigmentation, rosacea, skin barrier disorders
• Adjuvant in bullous pemphigoid, in combination with tetracyclines, individual therapy planning
• Adjuvant in HIV supportive therapy, in studies to reduce isoniazid-induced polyneuropathy

Nicotinamid is not suitable for lipid reduction because the lipid-lowering effects of vitamin B3 come exclusively from nicotinic acid and only in high doses. Self-medication with nicotinamid in cancer prevention should only be undertaken after individual dermatological consultation.

Dosage and Administration

Pellagra therapy: 100 to 500 mg per day orally, in severe cases 100 mg intravenously daily, transition to oral therapy after clinical stabilization.

Skin tumor prevention: 500 mg twice daily orally for at least 12 months according to study protocol in high-risk patients with multiple squamous cell carcinomas or basal cell carcinomas.

Topical application: 4 to 5 percent niacinamide creams one to two times daily, especially in the morning and evening applied in a thin layer.

Bullous pemphigoid (off label): 500 mg three times daily in combination with tetracyclines under dermatological supervision.

Administration: with or without meals. If stomach sensitive, take with meals. Swallow tablets whole without chewing, drink sufficient liquid.

Renal insufficiency: with eGFR below 30 ml per minute use caution, accumulation possible. Hepatic insufficiency: in severe functional impairment consider dose reduction because hepatic metabolism is relevant.

Side Effects

Rare: Nausea, stomach discomfort, heartburn, headache, dizziness.

At higher doses: Elevation of liver transaminases, in rare individual cases hepatitis. At daily doses over 3 g per day liver damage has been described.

Skin changes: with topical application rarely skin redness, burning, itching, especially during the adaptation phase.

No flushing: the typical flushing with skin redness, feeling of heat and pruritus that frequently occurs with nicotinic acid is largely absent with nicotinamid.

Metabolism: in individual studies under very high doses mild insulin resistance was observed, clinical significance within the scope of usual dosages is low.

Drug Interactions

• Tetracyclines (doxycycline, minocycline): synergistic effect in bullous pemphigoid, clinically desired combination, mutual pharmacokinetic interaction low.
• Carbamazepine, primidone, phenytoin: reduced levels of vitamin B3 possible, to be considered in pellagra prevention.
• Isoniazid: inhibits the endogenous synthesis of nicotinamid from tryptophan, therefore vitamin B6 and possibly B3 are supplemented in tuberculosis therapy.
• Statins: in combination with nicotinic acid increased myopathy risk, with nicotinamid practically not relevant.
• Antidiabetic agents: at very high doses possible moderate reduction in efficacy through insulin resistance, clinically rarely relevant.

Special Notes

Pregnancy: Nicotinamid in physiological doses safe, pellagra must be substituted. Breastfeeding: Transfer in small amounts, breastfeeding under therapeutic use possible.

Children: in pellagra substitute age-appropriately, other uses according to pediatric recommendation.

Liver disease: in pre-existing hepatopathy high doses must be critically examined, monitor liver values in the initial phase and during the course.

Cancer prevention: ONTRAC data apply to patients with multiple non-melanocytic skin tumors in the past five years. A blanket recommendation for all people is not derived. Individual dermatological consultation defines indication and therapy duration.

Lifestyle: Sun protection, avoidance of excessive UV exposure, regular skin cancer screening are the basis. Nicotinamid supplements but does not replace these measures.

Risk of confusion: Nicotinamid and nicotinic acid are not interchangeable. If prescribed niacin or nicotinic acid, you need a different substance, especially if the therapeutic goal is lipid reduction.

You may also be interested in

• Doxycycline, tetracycline in dermatological therapy
• Isotretinoin, retinoid in severe acne
• Tetracycline, classic tetracycline antibiotic
• Methotrexate, immunosuppressive in bullous dermatoses
• Dexpanthenol, pantothenic acid precursor in skin care

Frequently Asked Questions

Sources

• Gelbe Liste, Nicotinamid active ingredient profile
• BfArM, Federal Institute for Drugs and Medical Devices
• AWMF, Guidelines for skin tumors and pellagra
• DGE, Recommendations for vitamin B supply