Bioavailability of riboflavin for photodynamic laser therapy

We have a blue and UV laser in our Weber laser system, both of which we use consecutively intravascularly as a hemolaser with photodynamic substances for tumor patients and those with chronic persistent viral reactivation, based on the concept of Dr. Ruth Poglitsch and Dr. Michael Weber.

We use our extremely powerful 400mW red laser and the green laser primarily for mitochondrial diseases.

Riboflavin as a cheap photodynamic substance

Since there have been some discussions among colleagues about the optimal use of riboflavin, its application, and dosage, I have finally researched it for myself:

with our Weber laser system (100 mW Bluelaser at 441 nm and a UV-Laser 40 mW at 380 nm), you definitely have a photodynamic effect with riboflavin as a photosensitizer – even in two ideal wavelength ranges.

1. Riboflavin – Absorption Behavior
Riboflavin (vitamin B2) has two striking absorption maxima:

Approx. 375–380 nm (UV-A) → 380 nm UV laser is a perfect fit

Approx. 445 nm (blue light) → 441 nm blue light laser is also optimal

Both wavelengths efficiently activate riboflavin to form reactive oxygen species (ROS), particularly singlet oxygen (1O₂) and superoxide radicals, which is the basis of the photodynamic effect.

2. Efficacy of the laser system with riboflavin

• both colors are perfectly in the absorption spectrum of riboflavin.

3. Applications with Riboflavin + Weber System
The following PDT targets are possible in principle:

• Tumor cells (skin, mucous membranes, possibly subcutaneous, haemolaser)
  
• Bacterial biofilms, e.g., in cases of impaired wound healing or gum treatment – local
• Viral pathogens (herpes, HPV) with local application and as haemolaser
• Immunomodulation via ROS-induced danger signals (experimental: haemolaser)

Can riboflavin be administered orally for PDT, e.g., 1000 mg?

The oral bioavailability of riboflavin (vitamin B2) is dose-dependently limited. Here are the most important facts:

Riboflavin absorption limit – saturated transport mechanisms

Riboflavin is mainly actively absorbed in the proximal small intestine (duodenum and upper jejunum) via specific transporters (riboflavin transporters RFVTs).

These transporters are saturable – meaning that at higher doses, no more can be absorbed.

Maximum Absorption Rate

• For single doses above 30–50 mg, the active transport mechanism is largely saturated.
• Afterward, only minimal passive diffusion occurs, which is very inefficient.

• Studies show:
  • Up to approximately 30–40 mg: almost complete absorption
  • At 100 mg orally: only approximately 10–15% is absorbed
  • At 1000 mg orally: absorption continues to decline, typically below 5% (i.e., approximately 30–50 mg reach systemic)

Estimated values ​​for 1000mg oral riboflavin

Clinical Relevance

• Riboflavin is very well tolerated, with no known toxicity, as excess is excreted renally.
• At very high doses, the urine turns an intense yellow-orange color (riboflavinuria), which is harmless.
• Multiple doses spread throughout the day (e.g., 4 x 50 mg) are significantly more effective than a single dose of 1000 mg.

Summary

If you administer 1000 mg of riboflavin orally, only about 30–50 mg is actually absorbed. The remaining 950–970 mg is not absorbed and is excreted in the stool or partially in the urine (unchanged).

If you want to achieve a high systemic riboflavin concentration, parenteral administration (e.g., i.m./i.v.) or daily administration (several small doses) would be much more efficient.

Question: Can I optimize bioavailability with piperidine or DMSO?

Neither piperine nor DMSO are currently scientifically proven bioavailability enhancers for riboflavin. If maximum absorption is desired, fractionated administration of small doses or parenteral administration (e.g., infusion with B complex) should be used.

Question: How much riboflavin is needed for photodynamic therapy with blue/UV lasers?

For photodynamic therapy (PDT) with blue light or blue laser (wavelength approx. 400–470 nm) using riboflavin (vitamin B2) as a photosensitizer, the following applies:

Experimental or oncological photodynamics

For systemic PDT (e.g., against tumors, biofilm-forming bacteria, viral load in blood or skin), the following factors are crucial:

Light source

• Riboflavin absorbs strongly at approx. 375 nm (UVA) and 445 nm (Blue)
• Blue laser at 445 nm is optimal for activation

Minimal required riboflavin concentration in tissue/blood

• Studies show effective PDT effect at:
  • Plasma concentrations of 50–200 ng/ml (≈ 0.13–0.5 µmol/l)
• These concentrations can be achieved by:
  • i.v. Administration of 5–50 mg riboflavin
  • or fractionated oral administration of 50–100 mg riboflavin (divided over 1–2 hours)
• Higher oral doses do not lead to higher systemic concentrations, as absorption is limited

Recommended riboflavin dosage for PDT with blue laser

Practical protocol (e.g., skin/tumor/blood irradiation)

• 1 hour before PDT: 50 mg riboflavin orally
• 30 minutes before PDT: another 50 mg
• Irradiation with a 445 nm blue laser; for local treatment, energy density depends on the tissue depth, e.g., 10–40 J/cm²
• For local use (e.g., PDT for basal cell carcinoma): a topical 0.1% riboflavin solution can also be applied directly

Important information

• Riboflavin is light-sensitive – oral solutions should be taken in a light-protected manner.
• Excesses are quickly eliminated renally, therefore, they should be taken promptly before light application.
• DMSO or liposomes could possibly improve riboflavin diffusion into tissue locally, but are not necessary systemically.

Summary of oral riboflavin administration

For photodynamic therapy with a blue laser (445nm), 50–100mg of oral riboflavin is sufficient, divided over approximately 1–2 hours before light application. Alternatively: 10–25 mg i.v.. The goal is a short-term plasma concentration of at least 50 ng/ml to enable effective ROS production. Local applicationns (e.g., skin, cornea) use 0.1% riboflavin solutions directly at the target site.

Colleague uses 3 ampoules of Multivit-B forte

The use of 3 ampoules of Multivit-B® forte i.v. as a riboflavin source before photodynamic therapy (PDT) is feasible in principle, but only moderately effective in achieving the desired riboflavin effect.

Ingredients of 3 ampoules of Multivit-B® forte (total):

• Vitamin B1 (thiamine): 3 × 11mg = 33mg
• Vitamin B2 (riboflavin): 3 × 3.8mg = 11.4mg
• Vitamin B6 (pyridoxine): 3 × 3.8mg = 11.4mg
• Pantothenic acid: 3 × 6mg = 18mg
• Niacin (Nicotinamide): 3 × 110mg = 330mg

Riboflavin Dose Assessment

• The total riboflavin dose is 11.4 mg IV
  → This amount leads to safe, but short-term systemic availability
• Studies on PDT with riboflavin show:
  • Plasma concentrations of approximately 50–150 ng/ml are sufficient for effective ROS generation under laser irradiation
  • An IV dose of 10–25 mg riboflavin reliably achieves these concentrations

→ 11.4 mg IV riboflavin is therefore in the lower therapeutic range – effective, but not maximized.

Advantages of this strategy

• Intravenous: Bypasses limited intestinal absorption
• Rapid onset of action: Maximum plasma levels after a few minutes
• Safety profile: No toxicity, rapid degradation/elimination in case of excess

Disadvantages and Potential for Optimization

• Riboflavin content is low compared to the total injection (only 11.4 mg of approximately 400 mg total substance)
• Contains very high amounts of niacin (330 mg):
  • → Flushing reaction possible
  • → Can dilate vessels, potentially even lowering the local riboflavin concentration
• Possible option: pure riboflavin IV (10–25 mg) or high-dose B complex with ≥ 25 mg riboflavin per ampoule, if available

Summary

3 ampoules of Multivit-B forte IV before PDT deliver approximately 11.4 mg of riboflavin – this is at the lower end of the therapeutically effective range for photodynamic therapy. It is effective, but not ideal, especially if one is aiming for maximum oxidative effect.

Recommendation

• Either increase the dose (e.g., 4–5 ampoules)
• Or switch to preparation-specific riboflavin injections (e.g., 10 mg/ml riboflavin as a single dose)
• Alternatively, combine oral loading doses (e.g., 2 x 50 mg) plus IV booster

Several articles on photodynamic laser therapy

This is the most important one; all common photodynamic substances are examined and presented there, especially the inexpensive ones: riboflavin, curcumin, hypericin, methylene blue…

Photodynamische Therapie mit Laser und Photosensitizer

An older article: After this conference, we bought the Weber system.

Photodynamische Therapie von Krebs mittels Blut-Laserung und biologischer Farbstoffe

A short article also from around this time.

Photodynamische Krebs-Therapie

For psoriasis therapy, we use our Helbo Haemolaser

Psoriasis – mit dem Haemolaser tatsächlich Effekte