MikronährstoffCoach®: Mikronährstoffe / mikronaehrstoffcoach.com

Sources and physiological effects

Dietary sources
The term „niacin“ (formerly vitamin B₃) encompasses the two compounds nicotinic acid and nicotinamide. While nicotinic acid is contained primarily in vegetable foods, the amide form is found predominantly in animal tissues. Important sources of niacin are meat, offal, fish and yeast. Cereals provide medium quantities of niacin and is, primarly located in the aleurone layer of the plant. Heavy milling of grain results in high losses of niacin. In addition, the bioavailability of niacin from certain cereals (e.g. maize, millet) is sometimes not very high. Nicotinic acid is formed when coffee beans are roasted. A cup of coffee beans provides about 1 – 2 mg nicotinic acid. Unusually for a vitamin, niacin can also be produced in the body through the break down of the amino acid L-tryptophan. Foods rich in tryptophan such as eggs or milk can therefore contribute to meeting the demand for niacin. Both forms of niacin are relatively insensitive to oxygen, light and heat. Preparation losses are primarily caused by leaching, and amounting to about 15 % loss.
Physiological effects
Energy metabolism	In the form as nicotinamide adenine dinucleotide (NAD), it is involved in the citrate cycle, fatty acid oxidation and the respiratory chain
Lipid metabolism	By coupling to adipocyte receptors, niacin helps to lower LDL and triglyceride levels and increase HDL levels
Carbohydrate metabolism	As NADP it participates in the pentose phosphate cycle
Antioxidant	Regeneration of oxidized glutathione
Hormone synthesis	As an NADP cofactor of cholesterol and steroid hormone production

EFSA Health Claims

Health Claims		EFSA Opinon
Niacin	Contributes to a normal energy metabolism Contributes to normal cognitive function Contributes to the maintenance of normal skin Contributes to the reduction of fatigue and fatigue Contributes to the normal function of the nervous system Contributes to the maintenance of normal mucous membranes

Recommended intake

D-A-CH Recommended nutrient intake (Reference values EFSA and NHI )
	Age	Niacin (mg/d)
Infants (months)
	0-4	2
	4-12	5
Children (years)
	1-4	7
	4-7	10
	7-10	12
	10-13	14
	13-15	16
Youth/Adults (years)		Women	Men
	15-19	13	17
	19-25	13	17
	25-51	13	16
	51-65	13	15
	> 65	13	13
Pregnancy	15
Breastfeeding	17
Higher demand	Pregnancy, breast-feeding, sports, alcohol abuse, malnutrition, low tryptophan diet (maize, millet), malabsorption due to liver damage and diarrhea
Special groups at risk of deficiency	Anorexia (anorexia nervosa)

Recommended intake according to food labelling regulation		mg
(=100 % TB marking on the label) Niacin (niacin equivalents): 1 mg nicotinic acid = 1 mg NÄ 1 mg nicotinamide = 1 mg NÄ 60 mg tryptophan = 1 mg NÄ		16 mg
Nutrient safety
UL	Long-term daily intake at which no negative health effects are to be expected	35 mg/d
NOAEL	Maximum intake, with no observed adverse effect	Niacin 1500 mg Nicotinic acid 500 mg
Safety	The EFSA has been working on the safety of niacin.

Detailed information

Physiological significance of niacin

The designation niacin includes the two pyridine derivatives nicotinic acid and nicotinamide. Both have the same biological activity and can be metabolized into each other (1). Tissues with high metabolic rates such as immune cells, heart, liver, kidney and reproductive organs contain the highest levels of niacin. Nicotinamide, as a component of the hydrogen-transferring coenzymes NAD⁺/NADH and NADP⁺/NADPH, plays a central role in intermediate metabolism and thus contributes to the formation and breakdown of proteins, carbohydrates and fatty acids via numerous redox reactions. Niacin is also involved in the detoxification of xenobiotics, blood sugar regulation and antioxidant defense (2). Nicotinamide-containing NADPH regenerates spent glutathione by reduction (1). In addition, niacin is also involved in calcium homoeostasis, the formation of myelin sheaths and the repair and replication of DNA (2). Since tryptophan can also be used for NAD⁺- and NADP⁺-synthesis in addition to niacin, the requirement is expressed in niacin equivalents (NE). The self-synthesis, which can cover approx. 70 % of the niacin requirement, depends on a high-quality protein supply and sufficient vitamin B₆ intake (1).

Niacin deficiency symptoms

Niacin deficiency symptoms only appear when the tryptophan metabolism is disturbed or protein and vitamin B₆ intake is very low. In the early stages of niacin deficiency, unspecific symptoms such as weakness, loss of appetite, sleep problems and memory problems occur. A pronounced niacin deficiency leads to pellagra with the three typical DDD symptoms: dermatitis, diarrhea and dementia. Areas of skin exposed to light develop strong pigmentation, redness and increasing cornification. Mucosal inflammation, vomiting and diarrhea occur in the gastrointestinal tract. Disturbances of the nervous system only occur in cases of severe deficiency - nowadays only observed in developing countries.

Niacin in cardiovascular diseases

High-dose niacin in the form of nicotinic acid has long been used for intervention in hypercholesterolemia and, prior to the introduction of CSE inhibitors, was the drug of choice for dyslipidemia (2). However, clinical studies also document the effect of nicotinamide. For example, two double-blind, randomized studies show that nicotinamide administration, among other positive effects, effectively increased the HDL levels of patients (3) (4).

High LDL + low HDL = increased risk

Besides total cholesterol, the LDL level has proven to be a significant risk factor for cardiovascular disease. LDL values of >160 mg/dl in combination with HDL values of <45 mg/dl are considered particularly problematic. If the total cholesterol/HDL ratio is above 5, an increased cardiovascular risk must be assumed. Hypertriglyceridemia in combination with a quotient above 5 increases the risk of cardiovascular disease by a factor of 6 (1).

Therapeutic intervention to increase HDL levels

The control of elevated serum lipid levels through dietary measures and changes in lifestyle reaches a limits in effectiveness many patients. Epidemiological studies have shown that an increase in HDL levels can lead to a reduction in cardiovascular risk, irrespective of an increase in LDL and triglyceride levels (5). Niacin has long been used for intervention in hypercholesterolemia. Supplementation with niacin effectively reduces the plasma concentration of VLDL and LDL while increasing the HDL content (1) (6). The European Consensus Panel recommends the combination of up to 2 g niacin with statins for treatment of diabetics with hypercholesterolemia (7).

Niacin and Histamine

In very high doses nicotinic acid (not from niacin) can stimulate the release of histamines. This can lead to the appearance of “flush“ reactions characterized by skin redness and heat sensation. Dosages up to 500 mg seem to be well tolerated in this context (1).

Reference values

Parameter	Substrate	Reference value	Description of parameter/method
Niacin	EDTA- Whole Blood	1049 - 2202 µg/l	Individual parameter

Deficiency symptoms

Impact on	Symptoms
General health	Exhaustion, memory problems, muscle weakness, sleep disorders
Nerve system	Encephalopathies (tremor, rigor, spastic paresis)
Immune system	Susceptibility to infections
Mucous membrane	Glossitis, rhagades at the corner of the mouth, inflammations of the esophagus and GIT
Skin	Cracked flaky skin, strong pigmentation, increased cornification, pellagra (dermatitis, diarrhea and dementia)

Indications

Effect	Indications	Dosage
Physiological effects at low intake	For general preventive health support	20 - 50 mg/d
	For the targeted treatment of a niacin deficiency determined by medical diagnosis	500 - 1000 mg/d
	Therapeutic support for migraine and/or tension headaches	200 - 500 mg/d




Pharmacological effects at high intake	Therapeutic support for hyperlipidemia and hypercholesterolemia (as nicotinic acid)	1 - 3 g/d

Administration

General mode of administration
When	Niacin should be taken with meals.
Side effects
In very high doses nicotinic acid can cause a flush with skin redness, sensation of heat, itching and tingling. The simultaneous consumption of alcohol or coffee should be avoided to prevent a flush. In the case of a tendency to flow, a reduction can be achieved by premedication with an antihistamine (20 min before).
Contraindications
Acute myocardial infarction, acute gastric ulcers, arterial bleeding, gout, liver dysfunction

Interactions

Drug interactions
Antibiotics (especially Tetracycline)	Tetracyclines may affect the absorption and bioavailability of niacin.
Antiparkinson drugs (e.g. L-Dopa, Carbidopa, Benserazid)	Can cause a niacin deficiency if taken for long periods of time.
NSAIDs (e.g. ASS, Ibuprofen)	NSAIDs may reduce the side effects of niacin use (especially flushing).
Paracetamol	Nicotinamide may reduce the liver toxic effect of paracetamol.
Anti-epileptic drugs (carbamazepine)	Nicotinamide can reduce carbamazepine excretion in high doses.
Oral antidiabetic drugs (e.g. metformin, glimepiride, gliclazide, pioglitazone)	Nicotinic acid can increase the blood sugar lowering effect.
Cholesterol reduction drugs (statins, fibrates)	Nicotinic acid can increase the lipid modulating effect.
Nutrient interactions
Trace elements	Nicotinic acid and chromium have synergistic effects on blood sugar levels.
Vitamins	Niacin acts synergistically with all B vitamins, especially vitamin B₁ and B₆.
Amino acids	S-adenosylmethionine has protective effects on the liver at high niacin doses.

Description and related substances

Description

Water soluble B complex vitamin

Related substances

Nicotinic acid, nicotinamide, inositolhexanicotinate (inositolniacinate)
Nicotinic acid: is not used due to - flushing problem

References

Refezen

1) Hahn, A. et al. Ernährung. Physiologische Grundlagen, Prävention und Therapie. 2006.
2) Gröber, U. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte. 2008.
3) Steven, C. et al. 2008. A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients. Clin J Am Soc Nephrol. 3:1131–1138.
4) Shahbazian, H. et al. 2011. Oral nicotinamide reduces serum phosphorus, increases HDL, and induces thrombocytopenia in hemodialysis patients: a double-blind randomized clinical trial. Nefrologia. 31(1):58-65.
5) Toth, P. P. 2005. High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies. Am J Cardiol. 96(9A):50-8.
6) Wieneke, H. et al. 2005. Niacin – an additive therapeutic approach for optimizing lipid profile. Med Klin (Munich). 100(4):186-92.
7) Shepherd, J. et al. 2005. European Consensus Panel: Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel. Curr Med Res Opin. 21(5):665-82.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.