Vitamin B2

Vitamin B2 (riboflavin) helps convert food into energy and supports healthy skin, eyes, and nerves. Found in milk, eggs, meat, almonds, and mushrooms, most adults need 1.1-1.3 mg daily. Higher doses (400 mg) can effectively prevent migraines, reducing frequency by up to 50%. Riboflavin is especially beneficial for people with the MTHFR genetic variant. Deficiency causes cracks at the corners of the mouth, sore throat, and skin problems. Riboflavin is extremely safe with no known toxicity, though it turns urine bright yellow. This water-soluble vitamin is sensitive to light, so supplements should be stored in opaque containers.

Alternative Names: Riboflavin, Riboflavin-5-phosphate, Flavin mononucleotide (FMN), Flavin adenine dinucleotide (FAD)

Categories: Essential vitamin, B-complex vitamin, Water-soluble vitamin

Primary Longevity Benefits


  • Energy metabolism
  • Antioxidant protection
  • Cellular repair
  • Mitochondrial function

Secondary Benefits


  • Eye health
  • Skin health
  • Migraine prevention
  • Nerve function
  • Red blood cell formation
  • Detoxification support

Mechanism of Action


Vitamin B2 (riboflavin) serves as a crucial precursor to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential for numerous redox reactions in the body. These flavocoenzymes participate in the electron transport chain within mitochondria, playing a vital role in cellular energy production through ATP synthesis. Riboflavin-dependent enzymes are involved in the metabolism of carbohydrates, fats, and proteins, as well as in the conversion of other B vitamins (folate, niacin, vitamin B6) to their active forms. Riboflavin also contributes to antioxidant protection by supporting glutathione reductase, which regenerates reduced glutathione, a major cellular antioxidant.

Additionally, riboflavin is involved in the metabolism of medications and toxins through its role in the cytochrome P450 system. It supports methylation processes, iron metabolism, and the maintenance of homocysteine at healthy levels. In the nervous system, riboflavin is essential for myelin formation and maintenance. Its role in cellular energy production is particularly important for tissues with high energy demands, such as the heart, brain, and muscles.

Riboflavin also supports the conversion of tryptophan to niacin and the activation of vitamin B6, demonstrating its interconnected role within the B-vitamin complex.

Optimal Dosage


Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.

The Recommended Dietary Allowance (RDA) for riboflavin is 1.1-1.3 mg per day for adults, with slightly higher needs during pregnancy and lactation.

However , for optimal health benefits beyond preventing deficiency, many practitioners suggest higher intakes of 5-100 mg per day, particularly for specific health conditions or for individuals with genetic variations affecting riboflavin metabolism. Therapeutic doses for specific conditions may range from 25 mg to 400 mg daily, with the higher doses typically used for conditions like migraine prevention.

By Condition

Condition Dosage Notes
general health maintenance 1.3-5 mg/day Slightly above RDA for optimal cellular function
migraine prevention 200-400 mg/day Higher doses have shown effectiveness in reducing migraine frequency in clinical trials
MTHFR gene mutations 10-100 mg/day May support methylation pathways in those with certain genetic variations
eye health/cataracts 10-50 mg/day May help protect against oxidative damage to the lens
mitochondrial disorders 50-400 mg/day Higher doses may support energy production in certain mitochondrial conditions
glutathione support 10-50 mg/day Supports glutathione reductase activity for antioxidant protection

By Age Group

Age Group Dosage Notes
infants (0-12 months) 0.3-0.4 mg/day Through breast milk or formula; supplementation rarely needed
children (1-8 years) 0.5-0.6 mg/day RDA values; optimal intake may be higher
children (9-13 years) 0.9 mg/day RDA value; optimal intake may be higher
adolescents (14-18 years) 1.0-1.3 mg/day RDA values; higher end for males
adults (19-50 years) 1.1-1.3 mg/day (RDA); 5-25 mg/day (optimal) Higher end for men, lower end for women
older adults (50+ years) 1.1-1.3 mg/day (RDA); 5-50 mg/day (optimal) May benefit from higher doses due to decreased absorption efficiency and increased oxidative stress
pregnant women 1.4 mg/day Increased requirements during pregnancy
breastfeeding women 1.6 mg/day Increased requirements during lactation

Dosing Strategies

Migraine Prevention

  • 100 mg/day
  • Increase by 100 mg weekly until reaching 400 mg/day
  • 400 mg/day, typically for at least 3 months to assess effectiveness
  • Can be taken as a single daily dose or divided into two doses
  • Ongoing for as long as benefit is observed; may require 1-3 months to see full effect

MTHFR Support

  • 10-25 mg/day
  • May increase based on homocysteine levels and clinical response
  • 25-100 mg/day depending on individual response
  • Best absorbed with meals
  • Ongoing for genetic conditions; periodic assessment of homocysteine levels recommended

Mitochondrial Support

  • 50 mg/day
  • May increase gradually based on clinical response
  • 100-400 mg/day depending on condition and response
  • Divided doses with meals may improve tolerance
  • Typically ongoing for genetic mitochondrial disorders; periodic reassessment recommended

Special Populations

Athletes

  • Higher energy expenditure may increase riboflavin requirements
  • 5-25 mg/day
  • Particularly important during high-intensity training periods

Elderly

  • Decreased absorption efficiency; increased oxidative stress; medication interactions
  • 5-50 mg/day
  • Higher doses may be beneficial for those with multiple medications or chronic conditions

Vegetarians Vegans

  • Lower intake from food sources; may have higher requirements
  • 2-10 mg/day
  • Nutritional yeast is an excellent plant-based source

Alcohol Users

  • Alcohol may impair absorption and increase requirements
  • 5-25 mg/day
  • Higher end of range for heavy or chronic alcohol use

Genetic Variations

  • MTHFR C677T polymorphism increases riboflavin requirements
  • 10-100 mg/day
  • Higher doses may help normalize enzyme function in affected individuals

Bioavailability


Absorption Rate

Riboflavin absorption occurs primarily in the proximal small intestine through a carrier-mediated transport process. At typical dietary intake levels (1-2 mg), absorption efficiency is approximately 50-60%. This efficiency decreases as intake increases, with absorption dropping to around 15-20% at doses of 25 mg or higher. Once absorbed, riboflavin is converted to its coenzyme forms (FMN and FAD) in the intestinal mucosa and liver.

Unlike some other B vitamins, riboflavin has limited storage in the body, with small amounts primarily found in the liver, kidneys, and heart. Excess riboflavin is excreted in the urine, giving it a characteristic bright yellow color.

Absorption Mechanism

Primary Pathway: Carrier-mediated transport in the proximal small intestine

Transporters: Riboflavin transporters (RFVTs), particularly RFVT1, RFVT2, and RFVT3

Saturation Point: Absorption mechanism becomes saturated at doses above 25-30 mg, limiting efficiency at higher doses

Passive Diffusion: Limited passive diffusion occurs at higher doses, but is much less efficient than active transport

Factors Affecting Absorption

Enhancement Methods

Taking with food enhances absorption, Riboflavin-5-phosphate (activated form) may have better bioavailability than standard riboflavin, Dividing larger doses throughout the day improves overall absorption, Avoiding certain medications that interfere with absorption (antacids, phenobarbital, probenecid), Maintaining adequate thyroid function, as hypothyroidism can reduce conversion to active forms, Combining with other B vitamins for synergistic effects, Liposomal formulations may enhance cellular delivery (though limited research exists)

Timing Recommendations

Riboflavin is best absorbed when taken with meals, which stimulates the production of digestive enzymes and bile that aid in absorption. For general supplementation, dividing the daily dose and taking it with breakfast and lunch may optimize absorption and utilization. For those taking higher therapeutic doses (such as for migraine prevention), splitting into 2-3 doses throughout the day is recommended to maximize absorption. Since riboflavin can have a mild energizing effect through its role in energy metabolism, some individuals prefer to avoid taking it in the evening.

However, there is no strong evidence that timing significantly affects its efficacy for most people. Consistency in daily supplementation is generally more important than specific timing.

Form Comparison

Riboflavin

  • Moderate
  • 50-60% at low doses, 15-20% at high doses
  • Must be converted to FMN and FAD in the body
  • General supplementation, cost-effective approach

Riboflavin 5 Phosphate

  • Moderate to high
  • Potentially higher than standard riboflavin, especially in certain conditions
  • Pre-phosphorylated form (FMN) requiring fewer conversion steps
  • Those with conversion issues, certain genetic variations, or absorption challenges

Liposomal Riboflavin

  • Potentially high
  • Theoretical improvement in cellular delivery
  • Still requires conversion to active forms
  • Those seeking enhanced cellular delivery; limited research available

Metabolism And Excretion

Activation Process: Conversion to FMN by riboflavin kinase, then to FAD by FAD synthetase, primarily in intestinal cells and liver

Tissue Distribution: Highest concentrations in liver, kidneys, and heart; limited storage capacity

Half Life: Approximately 66-84 hours for body stores

Excretion: Primarily via urine as riboflavin and metabolites; gives urine characteristic bright yellow color

Recycling: Some salvage of riboflavin from degraded flavoproteins occurs

Special Populations

Elderly

  • May have reduced absorption efficiency
  • May benefit from riboflavin-5-phosphate form; taking with meals particularly important

Pregnant Women

  • Increased requirements but normal absorption mechanisms
  • Higher doses recommended (1.4 mg/day RDA)

Genetic Variations

  • MTHFR C677T polymorphism increases riboflavin requirements
  • Higher doses (10-100 mg/day) may be beneficial; riboflavin-5-phosphate may offer advantages

Gastrointestinal Disorders

  • Reduced absorption in conditions affecting small intestine
  • May require higher doses or riboflavin-5-phosphate form; monitoring for deficiency advised

Practical Recommendations

Take riboflavin supplements with meals for optimal absorption, For doses above 25-30 mg, divide into 2-3 doses throughout the day, Consider riboflavin-5-phosphate form if you have absorption issues or certain genetic variations, Be aware that high-dose supplementation will cause bright yellow urine (harmless), Store riboflavin supplements in opaque containers away from light to prevent degradation, If taking for migraine prevention, be consistent with daily intake and allow 1-3 months to assess effectiveness, Combining with other B vitamins may enhance overall effectiveness through synergistic actions

Safety Profile


Safety Rating i

5Very High Safety

Overview

Riboflavin (vitamin B2) has an excellent safety profile with minimal risk of adverse effects, even at doses substantially higher than the RDA. No Tolerable Upper Intake Level (UL) has been established because adverse effects have not been observed even at high intakes. The body efficiently eliminates excess riboflavin through the kidneys, resulting in bright yellow urine. While generally very safe, some individuals may experience mild side effects, particularly at higher doses.

Side Effects

Effect Severity Frequency Mechanism Management
Bright yellow urine Harmless Very common Excretion of excess riboflavin and metabolites Normal and expected; no management needed
Gastrointestinal discomfort Mild Rare Direct irritation at very high doses Taking with food; reducing dose; dividing into smaller doses
Itching or tingling sensation Mild Rare Unknown; possibly mild histamine release Reducing dose; dividing into smaller doses
Photosensitivity Mild to moderate Very rare Riboflavin can act as a photosensitizer at high doses Sun protection; reducing dose if problematic
Allergic reactions Mild to severe Extremely rare True allergy to riboflavin or excipients Discontinuation; medical attention for severe reactions

Contraindications

Condition Severity Evidence Notes
Known hypersensitivity to riboflavin Absolute contraindication Case reports of rare allergic reactions True riboflavin allergy is extremely rare
Pregnancy and breastfeeding at doses significantly above RDA Relative contraindication/caution Limited safety data for very high doses RDA doses (1.4-1.6 mg) are safe and recommended; moderate therapeutic doses likely safe but less studied
Rare riboflavin metabolism disorders Relative contraindication/caution Theoretical concern based on metabolic pathways Consult healthcare provider; may require specialized management

Drug Interactions

Medication Interaction Type Severity Mechanism Management
Antidepressants (tricyclics, MAOIs) Decreased riboflavin absorption/effectiveness Minor May interfere with riboflavin absorption or metabolism Monitor for riboflavin deficiency; may need increased supplementation
Phenobarbital and other anticonvulsants Increased riboflavin requirements Minor to moderate Enhance metabolism and excretion of riboflavin May need increased riboflavin supplementation
Probenecid Decreased riboflavin absorption Minor Interferes with renal tubular transport May need increased riboflavin supplementation
Antacids Decreased riboflavin absorption Minor Reduced absorption in less acidic environment Separate administration by at least 2 hours
Doxorubicin (chemotherapy drug) Increased riboflavin depletion Moderate Increased utilization or excretion Monitor for deficiency; consider supplementation
Chlorpromazine and other phenothiazines Increased riboflavin requirements Minor May interfere with riboflavin metabolism Monitor for deficiency; consider supplementation
Oral contraceptives Reduced riboflavin levels Minor Altered metabolism or increased requirements Consider supplementation, especially if low dietary intake

Upper Limit

No Tolerable Upper Intake Level (UL) has been established for riboflavin, as no adverse effects have been associated with high oral intakes from food or supplements. Doses of several hundred milligrams per day have been used in clinical studies for migraine prevention without significant adverse effects. The body efficiently eliminates excess riboflavin through the kidneys, resulting in bright yellow urine. As with any supplement,

it ‘s prudent to use the lowest effective dose for the intended purpose.

Safety In Special Populations

Children:

  • Excellent
  • Adjust dosing based on age and weight; bright yellow urine may cause concern if parents are not informed
  • Limited studies but no reported adverse effects at appropriate doses

Elderly:

  • Excellent
  • May have altered absorption or increased requirements; potential for more medication interactions
  • Well-tolerated in studies involving older adults

Pregnant Women:

  • Excellent at RDA doses
  • RDA is 1.4 mg/day; limited data on very high doses
  • No evidence of harm at RDA or moderately above; included in prenatal vitamins

Breastfeeding Women:

  • Excellent at RDA doses
  • RDA is 1.6 mg/day; passes into breast milk but beneficial for infant
  • No evidence of harm at RDA or moderately above; included in postnatal vitamins

Renal Impairment:

  • Generally good
  • Primarily excreted through kidneys; theoretical concern for accumulation in severe impairment
  • Limited studies but no reported significant issues

Hepatic Impairment:

  • Good
  • Liver involved in conversion to active forms; severe impairment might affect metabolism
  • Limited studies but no reported significant issues

Overdose Information

Acute Toxicity: No known cases of serious acute toxicity from oral riboflavin

Symptoms Of Excessive Intake: Primarily bright yellow urine; rarely mild gastrointestinal discomfort

Management: Discontinuation of high doses typically sufficient; supportive care for any symptoms

Antidote: None required; elimination occurs naturally through kidneys

Long Term Safety

Chronic High Dose Effects: No known adverse effects from long-term high-dose supplementation

Monitoring Recommendations: No specific monitoring required for most individuals; those with rare metabolic disorders may need specialized monitoring

Evidence From Clinical Trials: Studies using 400 mg daily for migraine prevention for 3-6 months showed excellent safety profile

Form Specific Safety

Riboflavin:

  • None significant
  • Excellent safety profile

Riboflavin 5 Phosphate:

  • None significant; potentially better tolerated in some individuals
  • Excellent safety profile; possibly advantageous for those with conversion issues

Practical Safety Recommendations

Practical Safety Recommendations

Start with lower doses and increase gradually if taking for therapeutic purposes, Be aware that bright yellow urine is normal and expected, Take with food to minimize potential for gastrointestinal discomfort, Inform healthcare providers about supplementation, especially if taking medications, For very high doses (200-400 mg for migraine prevention), consider medical supervision, Store properly away from light to maintain potency, Use reputable brands with quality testing to avoid contaminants

Synergistic Compounds


Compound: Other B vitamins (particularly B1, B3, B6, folate, B12)
Synergy Mechanism: B vitamins work together in many metabolic processes. Riboflavin is needed to activate other B vitamins, including conversion of B6 to its active form (PLP) and folate metabolism. Riboflavin also supports the conversion of tryptophan to niacin (B3). These interconnected pathways enhance the effectiveness of all B vitamins when administered together.
Evidence Rating: 5 – Extensive high-quality evidence
Clinical Evidence: Biochemical studies confirm the interdependence of B vitamins in metabolic pathways. Clinical evidence shows that B-complex supplementation often produces better outcomes than isolated B vitamins for conditions like homocysteine reduction and energy metabolism. Deficiency of one B vitamin frequently affects the function of others.
Optimal Ratio: No fixed optimal ratio established, but balanced B-complex formulations typically provide B vitamins in proportions that reflect their relative requirements. Therapeutic applications may require additional riboflavin beyond standard B-complex ratios.
Practical Applications: B-complex supplementation for general health maintenance; combined B vitamin therapy for homocysteine management; comprehensive B vitamin repletion in deficiency states.
Precautions: Generally very safe combination with minimal concerns; very high doses of individual B vitamins may theoretically create imbalances, but this is rarely observed clinically.

Compound: Magnesium
Synergy Mechanism: Riboflavin and magnesium work synergistically in energy metabolism and nervous system function. Magnesium is required for the activation of many enzymes that use riboflavin coenzymes (FAD and FMN). Both nutrients have been independently shown to help prevent migraines, and their combination may offer enhanced benefits through complementary mechanisms.
Evidence Rating: 4 – Strong evidence
Clinical Evidence: Biochemical studies confirm the cooperative roles of magnesium and riboflavin in enzymatic reactions. Clinical trials have shown benefit for both nutrients individually in migraine prevention. Some studies and clinical protocols combine them for enhanced effect, though direct comparative studies of the combination versus individual nutrients are limited.
Optimal Ratio: No established optimal ratio, but typical therapeutic combinations include 400 mg riboflavin with 300-600 mg magnesium daily for migraine prevention.
Practical Applications: Combined supplementation for migraine prevention; energy metabolism support; enhanced mitochondrial function.
Precautions: High-dose magnesium supplements can cause diarrhea; reduced doses needed in kidney disease; may interact with certain medications.

Compound: Coenzyme Q10
Synergy Mechanism: Both riboflavin and CoQ10 are essential for mitochondrial energy production, acting at different points in the electron transport chain. Riboflavin-dependent enzymes (through FAD) are involved in the early stages of the chain, while CoQ10 serves as an electron carrier in later stages. This combination provides comprehensive support for cellular energy production, particularly in high-energy demand tissues.
Evidence Rating: 3 – Moderate evidence
Clinical Evidence: Both nutrients independently show benefit for migraine prevention in clinical trials. Some studies and clinical protocols combine them for potentially enhanced effect. Mechanistic evidence strongly supports their complementary roles in mitochondrial function.
Optimal Ratio: No established optimal ratio, but typical therapeutic combinations include 400 mg riboflavin with 100-300 mg CoQ10 daily for migraine prevention or mitochondrial support.
Practical Applications: Combined approach for migraine prevention; mitochondrial support in fatigue conditions; potential benefits for cardiovascular health.
Precautions: CoQ10 may interact with blood thinners and reduce the effectiveness of some chemotherapy drugs; generally very safe combination.

Compound: Alpha-Lipoic Acid
Synergy Mechanism: Riboflavin and alpha-lipoic acid both support mitochondrial energy production and provide antioxidant protection through different mechanisms. Riboflavin supports glutathione regeneration through glutathione reductase, while alpha-lipoic acid directly regenerates glutathione and other antioxidants. This combination may provide enhanced protection against oxidative stress while supporting energy metabolism.
Evidence Rating: 3 – Moderate evidence
Clinical Evidence: Limited direct studies on the combination, but mechanistic evidence supports complementary roles in antioxidant protection and energy metabolism. Both have shown benefit in certain neurological conditions and diabetic complications individually.
Optimal Ratio: No established optimal ratio, but typical therapeutic combinations might include 100-400 mg riboflavin with 300-600 mg alpha-lipoic acid daily.
Practical Applications: Antioxidant support; mitochondrial function enhancement; potential benefits for diabetic neuropathy and other neurological conditions.
Precautions: Alpha-lipoic acid may lower blood sugar levels; monitoring recommended in diabetes. May interact with certain chemotherapy drugs.

Compound: Iron
Synergy Mechanism: Riboflavin is involved in iron metabolism, particularly in the mobilization of iron from storage. Riboflavin deficiency can impair iron utilization, potentially contributing to anemia even when iron intake is adequate. Conversely, iron is needed for certain flavoenzymes, creating a bidirectional relationship.
Evidence Rating: 3 – Moderate evidence
Clinical Evidence: Studies show that riboflavin supplementation can improve response to iron therapy in certain populations. Observational studies have found associations between riboflavin status and iron status markers.
Optimal Ratio: No established optimal ratio, but typical therapeutic combinations might include 5-25 mg riboflavin with 15-60 mg iron daily for deficiency states.
Practical Applications: Combined approach for certain types of anemia; comprehensive nutritional support during pregnancy; enhanced iron utilization in malabsorption conditions.
Precautions: Iron supplements can cause gastrointestinal side effects and should be properly dosed to avoid excess; separate from certain medications.

Stability Information


Overview

Riboflavin (vitamin B2) has moderate stability in dry form but is notably sensitive to light, which causes rapid degradation. Its stability is also affected by pH, temperature, and certain minerals. Understanding

these factors is crucial for proper storage, food preparation, and supplement formulation to ensure optimal potency and effectiveness. The distinctive bright yellow color of riboflavin makes its degradation visually apparent in many cases, as the color fades

when the vitamin breaks down.

Shelf Life

Typical Shelf Life: 2-3 years for most riboflavin supplements in solid form when properly stored in opaque containers

Form Specific Considerations: Generally stable in dry form when protected from light; typical shelf life of 2-3 years, Similar stability to standard riboflavin when protected from light, Shorter shelf life (1-2 years) due to potential hydrolysis in solution and increased susceptibility to photodegradation

Expiration Date Significance: Indicates manufacturer’s guarantee of potency, safety, and quality; gradual potency loss rather than sudden degradation typically occurs after expiration

Post Expiration Considerations: Riboflavin does not become toxic after expiration but may gradually lose potency; storage conditions (especially light exposure) have greater impact on actual stability than time alone

Storage Recommendations

General Guidelines: Store in opaque containers; protect from all light sources, especially sunlight and fluorescent lighting, Store at room temperature (59-77°F or 15-25°C); avoid high temperatures, Keep in dry place; moisture can accelerate degradation of solid forms, Keep in original opaque container; ensure tight closure after each use

Form Specific Recommendations: Store in original opaque container in cool, dry place; avoid bathroom medicine cabinets due to humidity and light exposure, Require strict protection from light; some may require refrigeration after opening; check label instructions, Highly susceptible to light degradation; store in opaque, airtight containers

Travel Considerations: For short trips, original containers preferred; for longer travel, consider solid forms in opaque, moisture-proof containers; avoid exposure to sunlight and heat

Degradation Factors

Factor: Light
Impact: Primary degradation factor; riboflavin is highly photosensitive
Mechanism: Light energy causes cleavage of the ribityl side chain and breakdown of the isoalloxazine ring structure
Practical Implications: Significant losses can occur in transparent containers or during food preparation in bright light
Prevention: Use opaque containers; minimize light exposure during processing and storage; amber or opaque packaging essential

Factor: pH
Impact: Riboflavin is most stable at pH 5-6 and becomes increasingly unstable in alkaline conditions
Mechanism: Alkaline conditions promote hydrolysis of the ribityl side chain and degradation of the isoalloxazine ring
Practical Implications: Riboflavin is relatively stable in acidic foods but may be rapidly lost in alkaline cooking conditions
Prevention: Avoid combining riboflavin supplements with alkaline substances; acidic food preparation methods better preserve riboflavin

Factor: Temperature
Impact: Heat accelerates riboflavin degradation, particularly in solution and when combined with light exposure
Mechanism: Thermal energy increases reaction rates for hydrolysis and oxidation
Practical Implications: Cooking, particularly with water (boiling, blanching), can cause significant riboflavin losses (20-40%)
Prevention: Minimize cooking time and water use; microwave cooking and steaming generally preserve more riboflavin than boiling

Factor: Oxygen
Impact: Oxygen contributes to riboflavin degradation, especially in solution and when exposed to light
Mechanism: Oxidation reactions affecting the isoalloxazine ring structure
Practical Implications: Aeration during food processing and storage can reduce riboflavin content
Prevention: Airtight packaging; minimize headspace in containers

Factor: Certain minerals
Impact: Some minerals, particularly iron and copper, can catalyze riboflavin degradation
Mechanism: Metal-catalyzed oxidation reactions
Practical Implications: Multivitamin/mineral formulations require careful formulation to prevent interactions
Prevention: Proper formulation with stabilizers; separate mineral and riboflavin supplementation if necessary

Factor: Reducing agents
Impact: Strong reducing agents can degrade riboflavin
Mechanism: Reduction of the isoalloxazine ring structure
Practical Implications: Certain food components or other supplements with reducing properties may affect stability
Prevention: Appropriate formulation; awareness of potential interactions

Stability Differences By Form

Riboflavin

  • Moderately stable in dry form when protected from light; highly unstable when exposed to light
  • Light exposure; packaging quality; humidity
  • Yellow color fades visibly when degradation occurs

Riboflavin 5 Phosphate

  • Similar light sensitivity to standard riboflavin; slightly more stable in certain pH conditions
  • Light exposure; packaging quality; formulation pH
  • More water-soluble than standard riboflavin

Liquid Formulations

  • Less stable than solid forms due to increased reactivity in solution
  • Light exposure; oxygen exposure; temperature; preservatives
  • Require strict light protection; may need refrigeration after opening

Packaging Considerations

Primary Packaging Types

Opaque Hdpe Bottles:
  • High-density polyethylene plastic bottles with light-blocking properties
  • Good light protection; moisture barrier; lightweight; durable; recyclable
  • Not completely impermeable to moisture or oxygen
  • Tablets, capsules, and most solid forms
Amber Glass Bottles:
  • Brown-tinted glass containers that block UV and most visible light
  • Excellent light protection; inert material; good barrier properties
  • Heavy; breakable; more expensive
  • Liquid formulations; premium products
Blister Packs:
  • Individual tablet/capsule cavities with foil or plastic backing
  • Protects unused units when some are consumed; convenient for travel; tamper-evident
  • Often insufficient light protection unless specifically designed with opaque materials
  • Unit-dose applications with appropriate light-blocking materials
Opaque Foil Pouches:
  • Sealed foil packets for powder or individual doses
  • Excellent light, moisture, and oxygen protection
  • Single use; more packaging material
  • Powder forms; products requiring maximum protection

Protective Features

Light Protection:
  • Opaque or amber containers that block UV and visible light
  • Critical for riboflavin stability
  • Store in original container; keep away from all light sources
Desiccants:
  • Moisture-absorbing packets or canisters included in containers
  • Helps maintain stability of solid forms
  • Leave in container; replace cap promptly after use
Oxygen Absorbers:
  • Packets that remove oxygen from container headspace
  • May help prevent oxidative degradation
  • Leave in container; replace cap promptly after use
Nitrogen Flushing:
  • Replacement of oxygen with nitrogen during packaging
  • Reduces oxidative degradation
  • Used in some premium supplements and liquid formulations

Stability Testing Methods

Stability In Food Processing

Stability Indicators For Consumers

Visual Indicators

Color Changes:
  • Fading of yellow color in riboflavin products
  • Indicates photodegradation
  • Replace if significant color change observed
Physical Changes:
  • Crumbling, excessive powder, spots, stickiness
  • May indicate moisture exposure or physical degradation
  • Replace if significant changes observed
Packaging Integrity:
  • Broken seals, punctures, improperly closed containers
  • Compromises protection from environmental factors, especially light
  • Replace if packaging integrity is compromised

Dissolution Changes

  • Tablets that fail to dissolve properly in water
  • May indicate reduced bioavailability
  • Place tablet in warm water; should show significant dissolution within 30 minutes
  • Not applicable to enteric-coated products; not a perfect predictor of in-vivo dissolution

Special Stability Considerations

Combination Products

B Complex Vitamins:
  • Generally compatible; riboflavin may sensitize other components to photodegradation
  • Strict protection from light; standard storage conditions sufficient
  • B vitamins work synergistically; minor losses may not significantly impact efficacy
Multivitamin Formulations:
  • Complex interactions possible; minerals may affect riboflavin stability
  • Follow package directions carefully; keep tightly closed and protected from light
  • Properly formulated products include stabilizers to minimize interactions
Riboflavin With Minerals:
  • Iron and copper can catalyze riboflavin degradation
  • Standard conditions; minimize light and moisture exposure
  • Properly formulated products include chelated minerals or separating agents

Enhanced Forms

Riboflavin 5 Phosphate:
  • Similar light sensitivity to standard riboflavin; slightly different pH stability profile
  • More water-soluble than standard riboflavin; may be more reactive in certain formulations
  • Standard storage conditions with strict light protection
Liposomal Forms:
  • Liposome integrity affected by temperature fluctuations and shear forces
  • May require refrigeration; avoid freezing or excessive heat
  • Follow specific storage instructions; protect from light

Practical Recommendations

Store riboflavin supplements in their original opaque containers, Keep containers tightly closed after each use, Store in cool, dry place away from all light sources, especially sunlight and fluorescent lighting, Avoid bathroom medicine cabinets due to humidity and light exposure, Check expiration dates before purchase and use, Be aware that fading of the yellow color indicates degradation, For travel, consider solid forms in opaque, moisture-resistant containers, If transferring to pill organizers, use opaque organizers and fill only 1-2 weeks at a time, To maximize riboflavin in cooking, use minimal water and shorter cooking times, Consider consuming cooking liquids (e.g., in soups or sauces) to recover leached riboflavin, Choose whole grains over refined grains to maximize riboflavin content, Store milk and dairy products in opaque containers and away from light, When in doubt about a product’s integrity, replacement is the safest option

Sourcing


Synthesis Methods

Industrial Synthesis Key Steps Quality Considerations Description Organisms Used Advantages Commercial Status
Typically synthesized through chemical processes involving condensation of barbituric acid derivatives with appropriate precursors
  • Synthesis of appropriate precursors
  • Condensation reactions to form the isoalloxazine ring structure
  • Purification and crystallization
Purity of starting materials; complete reaction; removal of synthesis byproducts; consistent crystallization
Some riboflavin production utilizes microbial fermentation processes Genetically modified bacteria (Bacillus subtilis), fungi (Ashbya gossypii), or yeast strains More environmentally sustainable; potentially more cost-effective for large-scale production Significant portion of global riboflavin production uses fermentation methods

Natural Sources

Animal Sources:

Food Serving Size Riboflavin Content Notes
Liver (beef, lamb) 100g 2.5-3.5 mg One of the richest natural sources; also high in other B vitamins
Kidney 100g 1.8-2.5 mg Excellent source but less commonly consumed
Eggs 1 large egg 0.2-0.3 mg Moderate source; riboflavin primarily in the white portion
Milk 1 cup (240ml) 0.3-0.4 mg Good source; light exposure can reduce content
Yogurt 1 cup (245g) 0.3-0.5 mg Good source; Greek yogurt may have slightly less due to whey removal
Cheese 100g 0.3-0.9 mg Content varies by type; aged cheeses typically higher
Plant Sources:

Food Serving Size Riboflavin Content Notes
Almonds 100g 0.8-1.0 mg One of the best plant sources
Mushrooms 100g 0.3-0.5 mg Content varies by variety; cremini and portobello higher
Spinach 100g cooked 0.2-0.3 mg Good plant source; cooking reduces volume significantly
Avocado 1 medium 0.1-0.2 mg Moderate source with healthy fats
Broccoli 100g cooked 0.1-0.2 mg Moderate source; light cooking preserves content
Whole grains 100g 0.1-0.3 mg Content varies by grain type; processing reduces content
Fortified Sources:

Food Serving Size Riboflavin Content Notes
Breakfast cereals 1 cup 0.4-1.7 mg Often fortified at 25-100% of daily value
Plant-based milks 1 cup (240ml) 0.3-0.5 mg Often fortified to match cow’s milk levels
Enriched bread 2 slices 0.2-0.3 mg Enrichment replaces some losses from refining
Energy bars 1 bar 0.2-1.7 mg Highly variable; check nutrition facts
Specialty Sources:

Food Serving Size Riboflavin Content Notes
Nutritional yeast 1 tablespoon 1.0-4.0 mg Excellent source; often fortified with additional B vitamins
Brewer’s yeast 1 tablespoon 0.3-0.7 mg Natural source with other B vitamins
Spirulina 1 tablespoon 0.2-0.3 mg Good plant-based source with other nutrients

Supplement Forms

The standard form of vitamin B2 used in most supplements
Advantages:

  • Cost-effective
  • Extensively studied
  • Widely available
  • Good stability in tablet form
Disadvantages:

  • Absorption efficiency decreases at higher doses
  • Requires conversion to active forms in the body
  • May cause bright yellow urine (harmless but can be concerning to some)
Best For: General health maintenance; prevention and treatment of deficiency in most cases; cost-conscious consumers; migraine prevention (at higher doses)
Typical Products: Most standard B-complex supplements; single B2 supplements; multivitamins
The phosphorylated form of riboflavin, also known as flavin mononucleotide (FMN), which is one of the active coenzyme forms
Advantages:

  • Pre-phosphorylated form requiring one less conversion step in the body
  • May have better absorption and utilization in certain conditions
  • Potentially more effective for individuals with conversion challenges
  • May be better utilized in certain genetic variations
Disadvantages:

  • More expensive than standard riboflavin
  • Less extensively studied for some applications
  • Still causes yellow urine
Best For: Individuals with absorption or conversion issues; those with certain genetic polymorphisms; those who haven’t responded to standard riboflavin
Typical Products: Professional-grade supplements; specialized formulations; some migraine formulas
Riboflavin encapsulated in liposomes (phospholipid spheres) for potentially enhanced delivery
Advantages:

  • Theoretical improvement in cellular delivery
  • May enhance absorption and bioavailability
  • Potentially reduced gastrointestinal side effects
Disadvantages:

  • Significantly more expensive than standard forms
  • Limited clinical research specifically on liposomal riboflavin
  • Variable quality among products
Best For: Those seeking enhanced absorption; individuals with sensitive digestive systems; those who haven’t responded to standard forms
Typical Products: Specialty supplements; premium formulations

Delivery Formats

Description Advantages Disadvantages Considerations
The most common form of riboflavin supplements
  • Cost-effective
  • Precise dosing
  • Good stability
  • Wide variety of dosages available
  • May be difficult to swallow for some
  • Some tablets may not disintegrate properly
  • Often contain binders and fillers
Look for products with demonstrated disintegration/dissolution properties; some tablets can be broken if swallowing is difficult
Riboflavin powder enclosed in a gelatin or vegetarian capsule
  • Easier to swallow than tablets for many people
  • Generally good disintegration
  • Often contain fewer additives
  • Usually more expensive than tablets
  • May contain gelatin (not suitable for vegetarians/vegans unless specified)
Vegetarian capsules (typically made from cellulose) are available for those avoiding animal products
Designed to dissolve under the tongue for direct absorption into the bloodstream
  • Bypasses first-pass metabolism
  • May be beneficial for those with absorption issues
  • Convenient for those with difficulty swallowing
  • More expensive than standard tablets
  • Limited evidence for superior bioavailability compared to regular oral forms for riboflavin
  • May have taste issues
May be worth considering for those with significant malabsorption issues
Riboflavin in solution form
  • Easy to swallow
  • Flexible dosing
  • Good option for those with swallowing difficulties
  • May have faster absorption
  • Often more expensive
  • May have shorter shelf life
  • Light sensitive – requires opaque container
  • May contain preservatives
  • Taste may be unpleasant
Particularly useful for elderly, children, or those with swallowing difficulties; must be protected from light
Loose powder for flexible dosing
  • Highly flexible dosing
  • Can be mixed with foods or beverages
  • Often fewer additives
  • May stain surfaces and skin yellow
  • Requires measuring
  • Taste may be unpleasant
  • Light sensitive
Store in opaque container; use measuring tools; be aware of staining potential

Quality Considerations

Item 1
Pharmacopeial Standards:

  • Official standards for identity, strength, quality, and purity
  • United States Pharmacopeia (USP), European Pharmacopoeia (Ph.Eur.), Japanese Pharmacopoeia (JP)
  • Ensures consistent quality and potency
Testing Methods:

  • HPLC, spectroscopic methods, fluorescence detection
  • Chromatographic methods to detect impurities
  • Quantitative analysis to confirm labeled amount
  • Ensures absence of harmful microorganisms
Third Party Certification:

  • Independent verification of quality and label claims
  • USP Verified, NSF Certified, ConsumerLab tested
  • Provides additional assurance of quality beyond manufacturer claims
Item 1
Factors Affecting Stability:

  • Light exposure (riboflavin is highly photosensitive)
  • Alkaline conditions (most stable at pH 5-6)
  • Heat (accelerates degradation, especially in solution)
  • Moisture (can accelerate degradation in solid forms)
Packaging Considerations: Opaque containers essential for light protection; moisture-resistant packaging for solid forms
Shelf Life Determinants: Storage conditions (especially light exposure); formulation; packaging quality
Item 1
Standard Riboflavin:

  • Purity; consistent potency; proper dissolution properties; light protection
  • Photodegradation; poor tablet disintegration; inconsistent potency
Riboflavin 5 Phosphate:

  • Verified identity of the phosphorylated form; stability; consistent potency
  • Mislabeling of form; higher cost not always reflecting higher quality
Liposomal Forms:

  • Liposome integrity; size consistency; encapsulation efficiency
  • Poor liposome formation; false claims of liposomal delivery; stability issues
Item 1
Manufacturer Considerations:

  • Reputation and history
  • Transparency about sourcing and testing
  • Good Manufacturing Practices (GMP) certification
  • Quality control procedures
Product Features:

  • Third-party testing or certification
  • Clear labeling of riboflavin form and amount
  • Appropriate packaging for stability (opaque containers)
  • Reasonable expiration dating
Red Flags:

  • Exaggerated claims
  • Unusually low prices for premium forms
  • Lack of transparency about manufacturing
  • Missing or vague supplement facts panel
  • Clear packaging that exposes riboflavin to light

Testing Methods

Erythrocyte Glutathione Reductase Activity Coefficient (EGRAC)
Description: Functional test measuring the activity of riboflavin-dependent enzyme glutathione reductase
Applications: Assessment of riboflavin status in clinical and research settings
Advantages: Reflects functional riboflavin status rather than just levels; considered gold standard
Limitations: Specialized test with limited availability in routine clinical practice
High-Performance Liquid Chromatography (HPLC)
Description: Separates and quantifies riboflavin and its metabolites
Applications: Determination of riboflavin content in supplements, foods, and biological samples
Advantages: High specificity and sensitivity; can distinguish between different forms
Limitations: Requires specialized equipment and trained personnel
Fluorometric Methods
Description: Utilizes riboflavin’s natural fluorescence properties
Applications: Quantification of riboflavin in various matrices
Advantages: High sensitivity; established methodology
Limitations: Potential interference from other compounds; requires careful sample preparation
Urinary Riboflavin Excretion
Description: Measures riboflavin and metabolites in urine
Applications: Assessment of recent riboflavin intake
Advantages: Non-invasive; relatively simple
Limitations: Reflects recent intake rather than tissue status; affected by kidney function
Mass Spectrometry
Description: Identifies and quantifies riboflavin based on mass-to-charge ratio
Applications: Research applications; advanced clinical testing
Advantages: Extremely high specificity and sensitivity; can identify metabolites
Limitations: Very expensive equipment; requires highly trained operators

Scientific Evidence


Evidence Rating i

4Evidence Rating: High Evidence – Multiple well-designed studies with consistent results

Overview

Riboflavin (vitamin B2) has strong scientific evidence supporting its essential role in human metabolism and the prevention and treatment of deficiency conditions. There is also substantial evidence for specific therapeutic applications beyond basic deficiency, particularly for migraine prevention and in individuals with the MTHFR C677T genetic polymorphism. Research continues to explore riboflavin’s potential benefits in eye health, cardiovascular protection, and mitochondrial disorders.

Key Studies

Study Title: High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre
Authors: Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G
Publication: European Journal of Neurology
Year: 2004
Doi: 10.1111/j.1468-1331.2004.00813.x
Url: https://pubmed.ncbi.nlm.nih.gov/15009163/
Study Type: Open-label clinical trial
Population: 23 patients with migraine
Findings: High-dose riboflavin (400 mg/day for 3 months) reduced migraine frequency from 4 days/month to 2 days/month and reduced migraine duration from 25.8 hours to 21.0 hours. Over half of the patients experienced a reduction in migraine frequency of at least 50%.
Limitations: Open-label design without placebo control; small sample size
Significance: Supports the use of high-dose riboflavin for migraine prevention; consistent with other studies showing benefit

Study Title: Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial
Authors: Schoenen J, Jacquy J, Lenaerts M
Publication: Neurology
Year: 1998
Doi: 10.1212/wnl.50.2.466
Url: https://pubmed.ncbi.nlm.nih.gov/9484373/
Study Type: Randomized, placebo-controlled trial
Population: 55 patients with migraine
Findings: High-dose riboflavin (400 mg/day for 3 months) was significantly superior to placebo in reducing migraine frequency and headache days. The proportion of patients who improved by at least 50% was 59% for riboflavin and 15% for placebo.
Limitations: Moderate sample size; single center study
Significance: One of the key placebo-controlled trials establishing riboflavin’s efficacy for migraine prevention

Study Title: Riboflavin supplementation and biomarkers of cardiovascular disease in the elderly
Authors: Hustad S, McKinley MC, McNulty H, Schneede J, Strain JJ, Scott JM, Ueland PM
Publication: Nutrition, Metabolism and Cardiovascular Diseases
Year: 2002
Doi: 10.1016/S0939-4753(02)80002-1
Url: https://pubmed.ncbi.nlm.nih.gov/12189908/
Study Type: Randomized controlled trial
Population: 79 healthy elderly individuals
Findings: Riboflavin supplementation (1.6 mg/day for 12 weeks) significantly improved riboflavin status and reduced plasma homocysteine levels, particularly in individuals with the MTHFR 677TT genotype, suggesting a role in cardiovascular health.
Limitations: Focus on biomarkers rather than clinical outcomes
Significance: Demonstrates riboflavin’s importance for homocysteine metabolism, particularly in genetically susceptible individuals

Study Title: Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C→T polymorphism in MTHFR
Authors: Horigan G, McNulty H, Ward M, Strain JJ, Purvis J, Scott JM
Publication: Journal of Hypertension
Year: 2010
Doi: 10.1097/HJH.0b013e32833a1f1b
Url: https://pubmed.ncbi.nlm.nih.gov/20027040/
Study Type: Randomized controlled trial
Population: 181 patients with premature cardiovascular disease
Findings: Riboflavin supplementation (1.6 mg/day for 16 weeks) significantly lowered blood pressure in patients with the MTHFR 677TT genotype but had no effect in those with CC or CT genotypes. This suggests a targeted role for riboflavin in managing hypertension in genetically at-risk individuals.
Limitations: Limited to specific genetic subgroup
Significance: Demonstrates personalized nutritional approach based on genetic factors; important for precision nutrition

Study Title: Riboflavin offers protection against oxidative stress, atherosclerosis and ischemia in diabetic rats
Authors: Alam MM, Iqbal S, Naseem I
Publication: Molecular and Cellular Biochemistry
Year: 2015
Doi: 10.1007/s11010-015-2404-4
Url: https://pubmed.ncbi.nlm.nih.gov/25929582/
Study Type: Animal study
Population: Diabetic rats
Findings: Riboflavin supplementation significantly reduced oxidative stress markers, improved antioxidant enzyme activities, and protected against atherosclerosis and ischemic damage in diabetic rats. The study suggests riboflavin may have protective effects against diabetic complications.
Limitations: Animal study; may not directly translate to humans
Significance: Provides mechanistic insights into riboflavin’s antioxidant and vascular protective effects

Meta Analyses

Title: Riboflavin (vitamin B2) and health
Authors: Powers HJ
Publication: American Journal of Clinical Nutrition
Year: 2003
Doi: 10.1093/ajcn/77.6.1352
Url: https://pubmed.ncbi.nlm.nih.gov/12791609/
Findings: Comprehensive review highlighting riboflavin’s roles in energy metabolism, antioxidant protection, and homocysteine metabolism. The review emphasizes riboflavin’s importance for cardiovascular health, particularly in individuals with the MTHFR 677TT genotype.
Included Studies: Broad review of clinical and mechanistic studies
Significance: Authoritative review establishing riboflavin’s diverse roles beyond basic deficiency

Title: Efficacy of vitamin B2 (riboflavin) in migraine prophylaxis: A systematic review
Authors: Thompson DF, Saluja HS
Publication: Journal of Clinical Pharmacy and Therapeutics
Year: 2017
Doi: 10.1111/jcpt.12548
Url: https://pubmed.ncbi.nlm.nih.gov/28485121/
Findings: Systematic review of 11 clinical trials found that high-dose riboflavin (typically 400 mg/day) was effective for migraine prophylaxis with minimal adverse effects. The number needed to treat was 2-3 patients to prevent one additional migraine attack.
Included Studies: 11 clinical trials of varying designs
Significance: Confirms riboflavin’s efficacy for migraine prevention across multiple studies

Title: B-vitamins and homocysteine metabolism: an update
Authors: Stover PJ
Publication: Nutrition Reviews
Year: 2010
Doi: 10.1111/j.1753-4887.2010.00340.x
Url: https://pubmed.ncbi.nlm.nih.gov/21091944/
Findings: Review highlighting the interconnected roles of B vitamins, including riboflavin, in homocysteine metabolism. Riboflavin is particularly important for individuals with the MTHFR 677TT genotype, as it stabilizes the enzyme and improves its function.
Included Studies: Mechanistic and clinical studies on B vitamins and homocysteine
Significance: Establishes riboflavin’s role in methylation pathways and genetic interactions

Evidence By Application

Deficiency Prevention And Treatment

  • 5 – Extensive high-quality evidence
  • Riboflavin is essential for human metabolism; deficiency leads to well-characterized conditions including angular stomatitis, cheilosis, and certain types of anemia; supplementation effectively prevents and treats these conditions
  • Supplementation indicated for high-risk populations (alcoholics, elderly, those with malabsorption conditions)

Migraine Prevention

  • 4 – Strong evidence
  • Multiple clinical trials show high-dose riboflavin (400 mg/day) reduces migraine frequency by approximately 50% in responders; effect typically takes 1-3 months to develop
  • Consider as first-line prophylactic option due to excellent safety profile; may be particularly suitable for patients who cannot tolerate pharmaceutical preventives

Genetic Polymorphisms

  • 4 – Strong evidence
  • Riboflavin supplementation significantly improves MTHFR enzyme function in individuals with the C677T polymorphism; reduces homocysteine levels and blood pressure in this genetic subgroup
  • Consider riboflavin supplementation for individuals with known MTHFR C677T genotype, particularly the TT genotype

Eye Health

  • 3 – Moderate evidence
  • Observational studies suggest associations between riboflavin status and reduced risk of cataracts and certain other eye conditions; limited intervention trials
  • May be considered as part of comprehensive eye health approach; more research needed

Mitochondrial Disorders

  • 3 – Moderate evidence
  • Case reports and small trials suggest benefit in certain mitochondrial disorders, particularly those affecting flavin-dependent enzymes; mechanistic plausibility based on role in electron transport chain
  • Consider as adjunctive therapy in specific mitochondrial disorders; individualized approach needed

Antioxidant Protection

  • 3 – Moderate evidence
  • Riboflavin supports glutathione reductase activity, enhancing antioxidant protection; animal and limited human studies show reduced oxidative stress markers with supplementation
  • May contribute to overall antioxidant strategy; particularly relevant in conditions with increased oxidative stress

Ongoing Research Areas

Area Current Status Key Hypotheses Notable Developments
Personalized nutrition based on genetic factors Active research area with promising findings for MTHFR polymorphisms Genetic variations affecting riboflavin-dependent enzymes may create higher requirements for optimal function Multiple studies confirming benefit in MTHFR C677T genotype; exploration of other relevant polymorphisms
Mitochondrial disorders and energy metabolism Emerging area with mechanistic rationale and preliminary clinical findings Riboflavin supplementation may support compromised mitochondrial function in various disorders Case reports of benefit in specific disorders; ongoing trials in broader populations
Neuroprotection and cognitive function Early-stage research with limited clinical data Riboflavin’s roles in energy metabolism, myelin formation, and antioxidant protection may benefit neurological health Animal studies showing neuroprotective effects; limited human trials underway
Metabolic health and diabetes complications Promising animal studies with limited human data Riboflavin may protect against diabetes complications through antioxidant effects and support of compromised metabolic pathways Animal studies showing protection against diabetic complications; human trials in planning stages

Ongoing Trials

Title: Riboflavin supplementation for prevention of migraine in children and adolescents
Status: Recruiting
Identifier: NCT04123366
Sponsor: Children’s Hospital of Philadelphia
Estimated Completion: 2023
Intervention: Riboflavin 200-400 mg daily based on weight
Primary Outcome: Reduction in migraine frequency

Title: High-dose riboflavin for treatment of multiple acyl-CoA dehydrogenase deficiency
Status: Active, not recruiting
Identifier: NCT03726346
Sponsor: University Hospital, Ghent
Estimated Completion: 2023
Intervention: Riboflavin 100-400 mg daily
Primary Outcome: Changes in acylcarnitine profile and clinical symptoms

Title: Riboflavin supplementation for blood pressure control in individuals with MTHFR gene variants
Status: Recruiting
Identifier: NCT04176016
Sponsor: Ulster University
Estimated Completion: 2024
Intervention: Riboflavin 10 mg daily
Primary Outcome: Blood pressure reduction in MTHFR 677TT genotype

Title: Riboflavin’s effects on oxidative stress markers in patients with diabetes
Status: Not yet recruiting
Identifier: NCT04209868
Sponsor: Cairo University
Estimated Completion: 2024
Intervention: Riboflavin 50 mg daily
Primary Outcome: Changes in oxidative stress biomarkers

Title: Combination of riboflavin, magnesium, and CoQ10 for migraine prevention
Status: Recruiting
Identifier: NCT03756896
Sponsor: Thomas Jefferson University
Estimated Completion: 2023
Intervention: Riboflavin 400 mg + magnesium 500 mg + CoQ10 150 mg daily
Primary Outcome: Reduction in migraine frequency compared to single agents

Title: Riboflavin supplementation for mitochondrial disorders
Status: Active, not recruiting
Identifier: NCT03647774
Sponsor: Children’s Hospital of Philadelphia
Estimated Completion: 2023
Intervention: Riboflavin 100-400 mg daily based on weight
Primary Outcome: Changes in mitochondrial function biomarkers

Evidence Quality Considerations

Strengths

  • Essential role in human metabolism firmly established
  • Clear deficiency syndromes with well-documented response to supplementation
  • Multiple randomized controlled trials for specific applications like migraine prevention
  • Strong mechanistic understanding of biochemical functions
  • Excellent safety profile allowing ethical studies with minimal risk

Limitations

  • Many studies have small sample sizes
  • Limited long-term follow-up data for many applications
  • Heterogeneity in dosing and outcome measures across studies
  • Publication bias may favor positive results
  • Optimal dosing not established for many applications
  • Limited biomarkers for assessing riboflavin status

Research Gaps

  • Optimal dosing strategies for various conditions
  • Long-term outcomes for preventive applications
  • Identification of additional genetic factors affecting requirements
  • Comparative effectiveness versus pharmaceutical alternatives
  • Potential synergies with other nutrients or medications
  • Effects in special populations (elderly, children, pregnant women)

Practical Evidence Interpretation

Strong evidence supports high-dose riboflavin (400 mg/day) for migraine prevention, Consider riboflavin supplementation for individuals with MTHFR C677T genotype, particularly TT homozygotes, Evidence for eye health, mitochondrial support, and antioxidant protection is promising but preliminary, The excellent safety profile of riboflavin means that therapeutic trials in individuals may be reasonable even where population-level evidence is still developing, Allow 1-3 months to assess effectiveness for migraine prevention, Consider riboflavin-5-phosphate form for individuals with absorption or conversion challenges, Combining with other nutrients (magnesium, CoQ10) may enhance effectiveness for certain applications, Cost-effectiveness is excellent compared to pharmaceutical alternatives for migraine prevention

Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.

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