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The Benefits of Vitamin B2 (Riboflavin)

The Benefits of Vitamin B2 (Riboflavin)

Introduction

Vitamin B2, also known as riboflavin, is a water-soluble B vitamin that plays crucial roles in cellular functions, growth, energy production, and metabolism of fats, drugs, and steroids (Suwannasom et al., 2020). It acts as a coenzyme in the forms of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential for various enzymatic reactions in the body. Riboflavin is naturally present in a wide variety of foods, including milk, meat, eggs, green vegetables, and fortified grains. It is also available as a dietary supplement.

Antioxidant and Anti-inflammatory Properties

Riboflavin has been shown to possess potent antioxidant, anti-ageing, anti-inflammatory, antinociceptive, and anti-cancer properties (Suwannasom et al., 2020). These beneficial effects are attributed to its ability to reduce oxidative stress and inflammation in various diseases. For instance, a study by Zou et al. (2015) demonstrated that riboflavin supplementation significantly extended the lifespan of fruit flies by enhancing the activity of antioxidant enzymes, such as glutathione reductase and catalase.

Furthermore, riboflavin has been found to activate the synthesis of normal extracellular matrix components and reduce reactive oxygen species (ROS) production in keratoconus, a progressive eye disorder characterised by thinning and distortion of the cornea (Cheung et al., 2014). These findings suggest that riboflavin may have therapeutic potential in managing oxidative stress-related conditions.

The Role of Riboflavin in Reducing Oxidative Stress

Oxidative stress occurs when there is an imbalance between the production of ROS and the body’s ability to neutralise them through antioxidant defences. Excessive ROS can cause damage to cellular components, including proteins, lipids, and DNA, leading to various pathological conditions. Riboflavin has been shown to combat oxidative stress through several mechanisms:

  1. Enhancing the activity of antioxidant enzymes: Riboflavin is a precursor for FAD, which is a cofactor for glutathione reductase, an enzyme that regenerates reduced glutathione (GSH) from its oxidised form (GSSG). GSH is a crucial endogenous antioxidant that scavenges ROS and protects cells from oxidative damage (Ashoori & Saedisomeolia, 2014).

  2. Directly scavenging ROS: Riboflavin can act as a direct antioxidant by donating electrons to neutralise ROS, such as singlet oxygen and superoxide anion (Cardoso et al., 2012).

  3. Inhibiting ROS production: Riboflavin has been shown to inhibit the activity of NADPH oxidase, an enzyme complex that generates superoxide anion, thereby reducing ROS formation (Mazur-Bialy et al., 2017).

Anti-inflammatory Effects of Riboflavin

Inflammation is a natural immune response to injury or infection; however, chronic inflammation can contribute to the development of various diseases, such as cardiovascular disorders, diabetes, and cancer. Riboflavin has been reported to exert anti-inflammatory effects by modulating the production of pro-inflammatory cytokines and mediators.

In a study by Mazur-Bialy et al. (2017), riboflavin treatment significantly reduced the release of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-mobility group box 1 (HMGB1) protein in lipopolysaccharide-stimulated macrophages. These findings suggest that riboflavin may have potential therapeutic applications in managing inflammatory conditions.

Migraine Prevention

Migraine is a debilitating neurological disorder characterised by recurrent episodes of severe headache, often accompanied by nausea, vomiting, and sensitivity to light and sound. Several studies have investigated the efficacy of riboflavin in preventing migraines, with promising results.

A randomised controlled trial by Schoenen et al. (1998) found that daily supplementation with 400 mg of riboflavin for three months significantly reduced the frequency and intensity of migraine attacks in adults compared to placebo. Similarly, a study by Condó et al. (2009) demonstrated that riboflavin prophylaxis at the same dosage and duration effectively reduced migraine frequency and severity in children and adolescents.

The American Academy of Neurology and the American Headache Society have concluded that riboflavin is probably effective for migraine prevention based on the available evidence (Holland et al., 2012). The exact mechanisms underlying riboflavin’s migraine-preventive effects are not fully understood; however, it is thought to involve the enhancement of mitochondrial energy metabolism and the reduction of oxidative stress in the brain (Boehnke et al., 2004).

Recommended Dosage for Migraine Prevention

The most commonly studied dosage of riboflavin for migraine prevention is 400 mg per day, typically divided into two 200 mg doses (Schoenen et al., 1998; Condó et al., 2009). This dosage has been shown to be well-tolerated, with no reported serious adverse effects. However, it is essential to consult a healthcare professional before starting any new supplement regimen, as individual needs may vary.

Potential Mechanisms of Action

The exact mechanisms by which riboflavin prevents migraines are not fully elucidated; however, several theories have been proposed:

  1. Enhancing mitochondrial energy metabolism: Riboflavin is a precursor for FMN and FAD, which are essential cofactors for the electron transport chain in mitochondria. Impaired mitochondrial function has been implicated in the pathogenesis of migraines (Yorns & Hardison, 2013). By improving mitochondrial energy production, riboflavin may help prevent migraine attacks.

  2. Reducing oxidative stress: Oxidative stress has been associated with the development and progression of migraines (Geyik et al., 2016). As discussed earlier, riboflavin possesses antioxidant properties and can help combat oxidative stress, which may contribute to its migraine-preventive effects.

  3. Modulating neurotransmitter levels: Riboflavin has been shown to influence the levels of certain neurotransmitters, such as serotonin and dopamine, which are involved in the pathophysiology of migraines (Marashly & Bohlega, 2017). By regulating these neurotransmitters, riboflavin may help prevent migraine attacks.

Eye Health

Riboflavin has been studied for its potential role in promoting eye health and preventing certain ocular disorders, such as cataracts and glaucoma.

Cataracts

Cataracts are a common age-related eye condition characterised by the clouding of the lens, leading to impaired vision. Several studies have investigated the relationship between riboflavin intake and the risk of developing cataracts.

The Blue Mountains Eye Study, a large prospective cohort study conducted in Australia, found that higher riboflavin intake was associated with a decreased risk of nuclear lens opacities, a type of cataract (Jacques et al., 2001). Participants in the highest quintile of riboflavin intake had a 34% lower risk of nuclear cataracts compared to those in the lowest quintile, after adjusting for potential confounders.

The protective effect of riboflavin against cataracts may be attributed to its antioxidant properties, as oxidative stress has been implicated in the development of age-related cataracts (Thiagarajan & Manikandan, 2013). By scavenging ROS and enhancing the activity of antioxidant enzymes, riboflavin may help prevent or delay the onset of cataracts.

Glaucoma

Glaucoma is a group of eye disorders characterised by progressive damage to the optic nerve, often associated with increased intraocular pressure. Some studies have suggested that riboflavin may have potential therapeutic applications in managing glaucoma.

In an animal study by Wang et al. (2015), riboflavin supplementation significantly reduced oxidative stress and apoptosis in the retinal ganglion cells of rats with experimentally induced glaucoma. These findings suggest that riboflavin may have neuroprotective effects in glaucoma; however, more research is needed to confirm its efficacy in humans.

Cancer Risk Reduction

The relationship between riboflavin intake and cancer risk has been investigated in several epidemiological studies, with mixed results. Some studies have suggested an inverse association between riboflavin intake and the risk of certain cancers, such as colorectal and lung cancer, while others have found no significant association.

Colorectal Cancer

A meta-analysis by Liu et al. (2015) examined the relationship between dietary riboflavin intake and colorectal cancer risk. The analysis included 13 observational studies (10 case-control and 3 cohort studies) with a total of 16,693 colorectal cancer cases. The results showed that higher dietary riboflavin intake was associated with a 12% lower risk of colorectal cancer compared to lower intake (relative risk [RR] = 0.88, 95% confidence interval [CI]: 0.81-0.95).

However, it is important to note that the majority of the included studies were case-control studies, which are more susceptible to bias compared to cohort studies. Additionally, the analysis did not account for potential confounding factors, such as other dietary components or lifestyle factors, which may have influenced the results.

Lung Cancer

The association between riboflavin intake and lung cancer risk has been investigated in several observational studies, with inconsistent findings. A prospective cohort study by Kabat et al. (2008) examined the relationship between dietary intake of B vitamins and lung cancer risk in 3,026 Canadian women. The study found no significant association between riboflavin intake and lung cancer risk after adjusting for potential confounders, such as age, smoking status, and total energy intake.

In contrast, a case-control study by Takata et al. (2012) found that higher dietary riboflavin intake was associated with a lower risk of lung cancer in a Chinese population. Participants in the highest quartile of riboflavin intake had a 45% lower risk of lung cancer compared to those in the lowest quartile (odds ratio [OR] = 0.55, 95% CI: 0.37-0.81), after adjusting for potential confounders.

The inconsistent findings regarding the association between riboflavin intake and lung cancer risk may be due to differences in study design, population characteristics, and dietary assessment methods. More well-designed prospective cohort studies are needed to clarify the relationship between riboflavin intake and lung cancer risk.

Potential Mechanisms of Cancer Risk Reduction

The potential mechanisms by which riboflavin may reduce cancer risk are not fully understood; however, several theories have been proposed:

  1. Antioxidant effects: As discussed earlier, riboflavin possesses antioxidant properties and can help combat oxidative stress, which has been implicated in the development and progression of various cancers (Suwannasom et al., 2020).

  2. Modulation of DNA repair: Riboflavin has been shown to influence the activity of enzymes involved in DNA repair, such as poly(ADP-ribose) polymerase (PARP) (Manthey et al., 2005). By promoting DNA repair, riboflavin may help prevent the accumulation of genetic damage that can lead to cancer.

  3. Regulation of cell growth and differentiation: Riboflavin has been reported to modulate the expression of genes involved in cell growth and differentiation, such as p53 and p21 (Manthey et al., 2005). By regulating these genes, riboflavin may help control cell proliferation and prevent the development of cancerous cells.

It is important to note that while some studies have suggested a potential protective effect of riboflavin against certain cancers, more research is needed to confirm these findings and elucidate the underlying mechanisms. Additionally, the optimal dosage and form of riboflavin for cancer risk reduction remain to be determined.

Iron Absorption and Anaemia Prevention

Riboflavin plays a crucial role in iron absorption and the prevention of anaemia, a condition characterised by a deficiency of healthy red blood cells or haemoglobin in the blood. Riboflavin is involved in the mobilisation of iron from storage sites, such as the liver and spleen, and its incorporation into haemoglobin (Powers et al., 1983).

A study by Powers et al. (2011) investigated the effect of correcting riboflavin deficiency on haematologic status in young women in the United Kingdom. The randomised, double-blind, placebo-controlled trial included 123 women aged 19-25 years with marginal riboflavin status. Participants were randomly assigned to receive either 2 mg or 4 mg of riboflavin or placebo daily for eight weeks. The results showed that riboflavin supplementation significantly improved haemoglobin and ferritin levels, indicating an improvement in iron status and a reduction in the risk of anaemia.

The mechanism by which riboflavin enhances iron absorption and utilisation is thought to involve the flavin-dependent enzyme, ferric reductase. This enzyme reduces ferric iron (Fe3+) to ferrous iron (Fe2+), which is the form of iron that is absorbed in the small intestine (Powers, 2003). By promoting the activity of ferric reductase, riboflavin may help improve iron absorption and prevent anaemia.

Riboflavin Deficiency and Anaemia

Riboflavin deficiency has been associated with an increased risk of anaemia, particularly in vulnerable populations, such as pregnant women and the elderly. A cross-sectional study by Ma et al. (2008) examined the relationship between riboflavin status and anaemia in pregnant Chinese women. The study included 1,149 pregnant women who underwent assessments of riboflavin status (using the erythrocyte glutathione reductase activation coefficient [EGRAC]) and haemoglobin levels. The results showed that women with riboflavin deficiency (EGRAC ≥ 1.4) had a significantly higher prevalence of anaemia compared to those with adequate riboflavin status (35.6% vs. 22.0%, p < 0.001).

Similarly, a study by Subramanian et al. (2016) investigated the association between riboflavin status and anaemia in elderly Indian adults. The study included 252 participants aged 60 years and above who underwent assessments of riboflavin status (using EGRAC) and haemoglobin levels. The results showed that participants with riboflavin deficiency (EGRAC ≥ 1.4) had a significantly higher prevalence of anaemia compared to those with adequate riboflavin status (58.3% vs. 31.7%, p < 0.001).

These findings highlight the importance of ensuring adequate riboflavin intake, particularly in populations at risk of deficiency, to prevent anaemia and its associated health consequences.

Recommended Dietary Allowance (RDA) and Sources

The recommended dietary allowance (RDA) for riboflavin varies by age and sex. The current RDAs for riboflavin, as established by the Food and Nutrition Board of the Institute of Medicine, are as follows (National Institutes of Health, 2022):

  • Infants 0-6 months: 0.3 mg/day (Adequate Intake [AI])
  • Infants 7-12 months: 0.4 mg/day (AI)
  • Children 1-3 years: 0.5 mg/day
  • Children 4-8 years: 0.6 mg/day
  • Children 9-13 years: 0.9 mg/day
  • Adolescents 14-18 years: 1.3 mg/day (males), 1.0 mg/day (females)
  • Adults 19+ years: 1.3 mg/day (males), 1.1 mg/day (females)
  • Pregnancy: 1.4 mg/day
  • Lactation: 1.6 mg/day

Riboflavin is widely distributed in foods, with some of the best sources being milk, meat, eggs, green vegetables, and fortified grains. Here are some common food sources of riboflavin and their approximate riboflavin content per serving (National Institutes of Health, 2022):

  • Beef liver, pan-fried (3 oz): 2.9 mg
  • Fortified breakfast cereal (1 cup): 1.7 mg
  • Yoghurt, plain, fat-free (1 cup): 0.6 mg
  • Milk, 2% fat (1 cup): 0.5 mg

Key Highlights and Actionable Tips

  • Riboflavin (vitamin B2) is essential for cellular functions, growth, energy production, and metabolism of fats, drugs, and steroids.
  • Riboflavin has potent antioxidant, anti-ageing, anti-inflammatory, antinociceptive, and anti-cancer properties, attributed to its ability to reduce oxidative stress and inflammation in various diseases.
  • Daily supplementation with 400 mg of riboflavin for three months has been shown to significantly reduce the frequency and intensity of migraine attacks in adults, children, and adolescents.
  • Higher riboflavin intake has been associated with a decreased risk of nuclear cataracts and may have potential therapeutic applications in managing glaucoma.
  • Riboflavin plays a crucial role in iron absorption and the prevention of anaemia by promoting the activity of the enzyme ferric reductase, which reduces ferric iron to ferrous iron for absorption in the small intestine.

Frequently Asked Questions

What are the best dietary sources of riboflavin?

Some of the best dietary sources of riboflavin include milk, meat, eggs, green vegetables, and fortified grains. For example, a 3-ounce serving of pan-fried beef liver contains 2.9 mg of riboflavin, while 1 cup of fortified breakfast cereal provides 1.7 mg. Other good sources include yoghurt, milk, and mushrooms.

How much riboflavin do I need daily, and does it vary by age and sex?

The recommended dietary allowance (RDA) for riboflavin varies by age and sex. For adults aged 19 years and older, the RDA is 1.3 mg/day for males and 1.1 mg/day for females. During pregnancy, the RDA increases to 1.4 mg/day, and during lactation, it rises to 1.6 mg/day. Children and adolescents have lower RDAs, ranging from 0.5 mg/day for ages 1-3 years to 0.9-1.3 mg/day for ages 9-18 years.

Can riboflavin supplements interact with medications?

Yes, riboflavin supplements can interact with certain medications. For example, riboflavin may reduce the effectiveness of anticholinergic drugs, phenothiazines (antipsychotic medications), and tetracycline antibiotics. It is essential to consult a healthcare professional before starting any new supplement regimen, especially if you are taking medications, to avoid potential interactions.

Are there any side effects associated with high riboflavin intake?

Riboflavin is generally well-tolerated, and no serious adverse effects have been reported with high intakes from food or supplements. However, consuming very high doses of riboflavin (400 mg or more per day) can cause your urine to turn a bright yellow colour, which is harmless but may be alarming if you are not aware of this effect.

How can I ensure I’m getting enough riboflavin in my diet?

To ensure you are getting enough riboflavin in your diet, consume a variety of riboflavin-rich foods, such as milk, meat, eggs, green vegetables, and fortified grains. If you follow a vegetarian or vegan diet, pay extra attention to including riboflavin-fortified foods and consider taking a B-complex supplement to meet your daily requirements. Consult a healthcare professional or registered dietitian for personalised advice on meeting your riboflavin needs.

References

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Boehnke, C., Reuter, U., Flach, U., Schuh-Hofer, S., Einhäupl, K. M., & Arnold, G. (2004). High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. European Journal of Neurology, 11(7), 475-477. https://doi.org/10.1111/j.1468-1331.2004.00813.x

Cardoso, D. R., Libardi, S. H., & Skibsted, L. H. (2012). Riboflavin as a photosensitizer. Effects on human health and food quality. Food & Function, 3(5), 487-502. https://doi.org/10.1039/c2fo10246c

Cheung, I. M. Y., Mcghee, C. N. J., & Sherwin, T. (2014). Beneficial effect of the antioxidant riboflavin on gene expression of extracellular matrix elements, antioxidants and oxidases in keratoconic stromal cells. Clinical and Experimental Optometry, 97(4), 349-355. https://doi.org/10.1111/cxo.12139

Condó, M., Posar, A., Arbizzani, A., & Parmeggiani, A. (2009). Riboflavin prophylaxis in pediatric and adolescent migraine. The Journal of Headache and Pain, 10(5), 361-365. https://doi.org/10.1007/s10194-009-0142-2

Geyik, S., Altunısık, E., Neyal, A. M., & Taysi, S. (2016). Oxidative stress and DNA damage in patients with migraine. The Journal of Headache and Pain, 17(1), 10. https://doi.org/10.1186/s10194-016-0606-0

Holland, S., Silberstein, S. D., Freitag, F., Dodick, D. W., Argoff, C., & Ashman, E. (2012). Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology, 78(17), 1346-1353. https://doi.org/10.1212/wnl.0b013e3182535d0c

Jacques, P. F., Chylack Jr, L. T., Hankinson, S. E., Khu, P. M., Rogers, G., Friend, J., … & Taylor, A. (2001). Long-term nutrient intake and early age-related nuclear lens opacities. Archives of Ophthalmology, 119(7), 1009-1019. https://doi.org/10.1001/archopht.119.7.1009

Kabat, G. C., Miller, A. B., Jain, M., & Rohan, T. E. (2008). Dietary intake of selected B vitamins in relation to risk of major cancers in women. British Journal of Cancer, 99(5), 816-821. https://doi.org/10.1038/sj.bjc.6604540

Liu, Y., Yu, Q., Zhu, Z., Zhang, J., Chen, M., Tang, P., & Li, K. (2015). Vitamin and multiple-vitamin supplement intake and incidence of colorectal cancer: a meta-analysis of cohort studies. Medical Oncology, 32(1), 434. https://doi.org/10.1007/s12032-014-0434-5

Ma, A. G., Schouten, E. G., Zhang, F. Z., Kok, F. J., Yang, F., Jiang, D. C., … & Sun, Y. Y. (2008). Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic acid supplements. The Journal of Nutrition, 138(10), 1946-1950. https://doi.org/10.1093/jn/138.10.1946

Manthey, K. C., Rodriguez-Melendez, R., Hoi, J. T., & Zempleni, J. (2005). Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering arrest in G1 phase of the cell cycle. The Journal of Nutritional Biochemistry, 17(4), 250-256. https://doi.org/10.1016/j.jnutbio.2005.05.005

Marashly, E. T., & Bohlega, S. A. (2017). Riboflavin has neuroprotective potential: focus on Parkinson’s disease and migraine. Frontiers in Neurology, 8, 333. https://doi.org/10.3389/fneur.2017.00333

Mazur-Bialy, A. I., Buchala, B., & Plytycz, B. (2017). Riboflavin deprivation inhibits macrophage viability and activity – a study on the RAW 264.7 cell line. British Journal of Nutrition, 118(7), 509-514. https://doi.org/10.1017/S0007114517002434

National Institutes of Health. (2022). Riboflavin: Fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/

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Powers, H. J., Hill, M. H., Mushtaq, S., Dainty, J. R., Majsak-Newman, G., & Williams, E. A. (2011). Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). The American Journal of Clinical Nutrition, 93(6), 1274-1284. https://doi.org/10.3945/ajcn.110.008409

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Subramanian, V. S., Kapadia, R., Ghosal, A., & Said, H. M. (2016). Identification of residues/sequences in the human riboflavin transporter-2 that is important for function and cell biology. Nutrition & Metabolism, 13(1), 89. https://doi.org/10.1186/s12986-016-0148-0

Suwannasom, N., Kao, I., Pruß, A., Georgieva, R., & Bäumler, H. (2020). Riboflavin: The health benefits of a forgotten natural vitamin. International Journal of Molecular Sciences, 21(3), 950. https://doi.org/10.3390/ijms21030950

Takata, Y., Cai, Q., Beeghly-Fadiel, A., Li, H., Shrubsole, M. J., Ji, B. T., … & Shu, X. O. (2012). Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China. Cancer Causes & Control, 23(12), 1965-1975. https://doi.org/10.1007/s10552-012-0074-z

Thiagarajan, R., & Manikandan, R. (2013). Antioxidants and cataract. Free Radical Research, 47(5), 337-345. https://doi.org/10.3109/10715762.2013.777155

Wang, X., Shen, M., Zhu, X., Xu, Y., Xu, X., & Shi, X. (2015). Protective effect of riboflavin on retinal oxidative damage via activating the Nrf2/HO-1 pathway in vivo and in vitro. The Journal of Nutritional Biochemistry, 26(12), 1526-1536. https://doi.org/10.1016/j.jnutbio.2015.07.022

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Zou, Y. X., Ruan, M. H., Luan, J., Feng, X., Chen, S., & Chu, Z. Y. (2017). Anti-aging effect of riboflavin via endogenous antioxidant in fruit fly Drosophila melanogaster. Journal of Nutrition Health & Aging, 21(3), 314-319. https://doi.org/10.1007/s12603-016-0752-8

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