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Sources and physiological effects

Dietary sources
Vitamin B₂is a water-soluble, B-complex vitamin, which is popularly known as the “growth vitamin“. As a cellular component of animals and plants, it is found in numerous foods usually in its bound form: flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) or protein bound. The most important vitamin B₂sources in the diet include milk and milk products, eggs, meat and offal. Cereals, fruit and vegetables contain only low concentrations of B₂. Vitamin B₂ is poorly soluble in water, very heat-stable, but highly light-sensitive. On average, 20 % of vitamin B₂ is destroyed during storage and food preparation. The storage of milk in a clear glass bottle under the influence of light is particularly unfavorable with 80% vitamin destruction.
Physiological effects
Energy metabolism	Cofactor in the respiratory chain
Lipid metabolism	Participating as coenzyme in the biosynthesis of cholesterol and in the oxidation of fatty acids
Homocysteine metabolism	As coenzyme of methylene THF reductase responsible for maintaining physiological homocysteine levels
Cellular immune system	As cofactor of phagocytosis involved in the defense against bacterial infections
Hormone balance	Synthesis of adrenalin
Antioxidant	Reduction of oxidized to reduced glutathione

EFSA Health Claims

Health claims
Vitamin B₂	Contributes to a normal energy metabolism Contributes to normal functioning of the nervous system Contributes to the preservation of normal mucous membranes Contributes to the maintenance of normal red blood cells Contributes to the maintenance of normal skin Contributes to the maintenance of normal vision Contributes to normal iron metabolism Contributes to the protection of cells against oxidative stress Contributes to the reduction of fatigue and fatigue

Recommended intake

D-A-CH recommended nutrient intake (Reference values EFSA and NHI )
	Age	Vitamin B₂(mg/d)
Infants (months)
	0-4	0.3
	4-12	0.4
Children (years)
	1-4	0.7
	4-7	0.9
	7-10	1.1
	10-13	1.3
	13-15	1.5
Teenagers/adults (years)		Women	Men
	15-19	1.2	1.5
	19-25	1.2	1.5
	25-51	1.2	1.4
	51-65	1.2	1.3
	> 65	1.2	1.2
Pregnacy	1.5
Breast-feeding	1.6
Increased need	Pregnancy, breastfeeding, competitive sports, trauma, alcohol abuse, chronic respiratory diseases, intestinal mycoses

Recommended intake according to food labelling regulations		mg
(=100 % TB marking on label)		1.4 mg
Nutrient safety
UL	Long-term daily intake, for which no negative effects on health are to be expected	N/A
NOAEL	Maximum intake, with no observed adverse effect.	200 mg

Detailed information

Vitamin B₂ for hypertension

Hypertension is one of the major risk factors for cardiovascular disease and heart attack. Elevated homocysteine levels in the blood often occur with a genetic defect that affects the enzyme methylenetetrahydrofolate reductase (MTHFR). This genetic defect occurs in the population at a relatively high incidence of up to 32 %. Vitamin B₂ is required as a cofactor for the synthesis of MTHFR, and an insufficient vitamin _B2 supply is suspected to be associated with the development of hypertension. Studies have shown that in people with a genetic predisposition to cardiovascular disease (MTHFR-677TT genotype) blood pressure can be controlled very well with vitamin B supplementation (1)(2).

Vitamin B₂ in migraine prevention

The prophylactic treatment of migraine is still a challenge. There is an abundance of drugs on the market, but most of them have severe side effects. Clinical studies have shown that supplementation with vitamin B₂ is an effective migraine prophylaxis. Vitamin B₂ significantly reduced both the number of migraine attacks per month and the average duration of attacks (3, 4).

Reference values

Parameter	Substrat	Referenzwert	Description
Riboflavin	whole blood	80 - 200 µg/l	Fasting (12 h food restriction). Transport: protected from light. Metabolites FAD, FMN and free riboflavin are determined and total riboflavin is calculated from these.
Erythrocyte Glutathione Reductase (EGR) Stimulation Test	Erythrocyte hemolysate (activity coefficient)	>1,3 boundary value 1,20-1,29	EGR is activated by FAD. Detection of riboflavin status by measuring activity without and with addition of FAD.
Interpretation
Diminished values or increased activity coefficient		Vitamin-B₁-deficiency
Increased values		Taking vitamin B₂ preparations or vitamin B complex preparations

Nutrigenetics
Certain gene sites and their effects on vitamin requirements

Gen

rsNumber

Risk SNP

Description

Recommended nutrients

MTHFR

rs1801133

T

Transmethylation by this enzyme is reduced, and the need for folic acid and vitamin B6 is increased. This SNP is associated with increased homocysteine levels. Vitamin B2 (riboflavin) can increase the activity of the MTHFR enzyme, so increased intake is recommended. Vitamin B6 and folic acid should always be taken together with vitamin B12 (5)(6)(7)(8).

B₂, B₆, B₁₂ und folic acid

Deficiency symptoms

Impact on	Symptoms
Skin	Redness, scaling, seborrheic dermatitis, glossitis, rhagades of the corner of the mouth
Nervous system	Muscle weakness, fatigue, peripheral neuropathies
Eyes	Keratitis, photosensitivity, vascularization of the cornea
Blood	Normochromic normocytic anemia, hyperhomocysteinemia

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	General prevention	5- 20 mg/d
	For increased demands during pregnancy and breastfeeding	5 - 20 mg/d





Pharmacological effects at a high intake	For migraine and for seizure prophylaxis	100 - 200 mg/d

Administration

General mode of administration
When	B vitamins can be taken with or between meals.
Side effects
High doses of vitamin B₂ are excreted relatively quickly by the kidneys and sometimes lead to a strong yellowing of the urine.
Contraindications
There are no contraindications known to date.

Interactions

Drug interactions
Tricyclic antidepressants	Hinder the incorporation of vitamin B₂in FAD and FMN and lead to increased vitamin B₂ excretion
Antiepileptics (e.g. carbamazepine)	Antiepileptics (e.g. carbamazepine)
Oral contraceptives	Long-term use of contraceptives can lead to disorders in vitamin B₂ status.
Thyroid medicines (thyroxine)	Promotes the formation of FAD and FMN from vitamin B₂. Vitamin B₂ is important for thyroxine synthesis.
Nutrient interactions
Trace elements	Vitamin B₂ deficiency affects the absorption of calcium, iron and zinc. High doses of boron can form complexes with vitamin B₂.
Vitamins	Vitamin B₂ works synergistically with all B vitamins. Vitamin B₂ protects vitamin E from lipid peroxidation.

Description and related substances

Description of the micronutrient

Water soluble vitamin of the B complex

Related substances

Riboflavin, Riboflavin-5‘ -Phosphate
Is also approved as a yellow food coloring (E101).

References

1) Wilson, C. P. et al. 2012. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up. Am J Clin Nutr.95(3):766-72. doi: 10.3945/ajcn.111.026245.
2) Wilson, C. P. et al. 2013. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial. Hypertension. 61(6):1302-8. doi: 10.1161/HYPERTENSIONAHA.111.01047.
3) Boehnke, C. et al. 2004. High-dose riboflavin treatment is efficacious in migraine prophylaxis:an open study in a tertiary care. European Journal of Neurology. 11: 475–477.
4) Namazi, N. et al. 2015. Supplementation with Riboflavin (Vitamin B2) for Migraine Prophylaxis in Adults and Children: A Review. International Journal for Vitamin and Nutrition Research. 85(1-2):79–87.
5) Olteanu, H. Munson, T. Banerjee, R. 2002. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 41(45):13378-85. .
6) Wilson, A. et al. 1999. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab. (4):317-23.
7) Seibold, P. et al. Polymorphisms in oxidative stress-related genes and postmenopausal breast cancer risk. Int J Cancer. 129(6):1467-76.
8) Jiang-Hua, Q. et al. 2014. Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B 12 intakes. Tumour Biol. 35(12):11895-901.

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.