Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections

Discussion in 'Scientific Studies' started by haidut, Apr 18, 2016.

  1. haidut

    haidut Member

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    Peat said in one of his interviews that vitamin B2, together with vitamin B1, selenium, vitamin K and CoQ10 are the most important substances for optimal mitochondrial function. I have been researching vitamin B2 and continue to be amazed at how underestimated this nutrient is both in mainstream medicine and in the blogosphere. As many people on the forum know, endotoxin is one of the most important factors involved in suppressing oxidative metabolism and suppressing its production or effects has a host of beneficial effects on overall health and even maximum lifespan. While drugs like methylene blue, mianserin, cyproheptadine, emodin, etc all have their place in the treatment of endotoxemia, vitamin B2 is unique among this group of substances due to its lack of any known side effects. In fact, its safety has earned it a status of food coloring agent that can be used in pretty much any dose the food vendor desires.
    These studies below show that vitamin B2, and especially its activated form riboflavin '5 phosphate (R5P), is remarkably effective in inhibiting the systemic effects of endotoxin, including the development of sepsis, as well as other bacterial infections with gram-negative and gram-positive pathogens EVEN after sepsis had already started. In addition, R5P was highly effective in lowering excessive NO production triggered by endotoxin and it seems that adding the amino acid valine greatly enhances the effectiveness of R5P and allows for lower doses to be used to achieve the same effects. Given that riboflavin is a cofactor of the enzyme MAO-A, and that enzyme is inhibited by methylene bue, it looks like the combination of riboflavin and methylene blue can be highly synergistic for issues related to endotoxin and excessive NO synthesis. While the studies did not look into the effects of R5P on serotonin, the role of R5P on MAO-A functionality suggests that some of its beneficial effects on endotoxemia, sepsis and bacterial infections can be at least partly due to its effects of increasing serotonin degradation.
    The human equivalent doses were high and given via the IV route. However, oral R5P is very well absorbed and has 90%+ bioavailability, so oral route is also possible. The minimum effective human equivalent oral doses for the combination of R5P and valine were approximately 0.2mg/kg and 25mg/kg respectively. This assumes bioavailability of 90% and 70% for R5P and valine.

    Enhancement of resistance to bacterial infection in mice by vitamin B2. - PubMed - NCBI
    "...We found that the intramuscular injection of vitamin B2 enhanced host resistance to E. coli infection in a dose-dependent manner (6.25 mg/kg-100 mg/kg). Furthermore, VB2 exhibited the protective activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Actinobacillus pleuropneumoniae. The mechanism of action of VB2 for enhancing resistance in mice may be, at least in part, its ability to stimulate the multiplication of neutrophils and monocytes, and to activate macrophages."

    Potentiation by amino acid of the therapeutic effect of highly purified vitamin B2 in mice with lipopolysaccharide-induced shock. - PubMed - NCBI
    "...Although aminolevane solution showed no improvement in the lipopolysaccharide-induced mortality, the therapeutic effect of vitamin B2 on endotoxin-induced shock was significantly enhanced by this amino acid supplement. Among the amino acid constituents of aminolevane solution, valine was the most effective in combination therapy of vitamin B2. Vitamin B2 diminished the elevations of interleukin-6 and lactic acid, and ameliorated the increased glucose consumption in lipopolysaccharide-stimulated mouse peritoneal macrophages. The rate of glucose utilization in peritoneal macrophages has been used as an index of lipopolysaccharide-induced activation (Ryan et al., 1979). We speculated that vitamin B2 could play a role in normalizing the energy production of macrophages. Lactic acidosis was reported to increase TNF-a production by rat peritoneal macrophages (Jensen et al., 1990). Further, TNF-a-induced excessive interleukin-6 production is well-known to occur, so lactic acidosis might have induced the excessive produc- tion of interleukin-6 observed in our experiment. The survivors had significantly lower initial lactate levels than nonsurvivors, and were able to significantly decrease their lactate levels over the course of their treatment (Morgan and Machiedo, 2002)."

    Highly purified vitamin B2 presents a promising therapeutic strategy for sepsis and septic shock. - PubMed - NCBI
    "...Vitamin B2 was administered with a bolus injection 6 h after LPS injection. The survival rate of the control group was 10% (2 of 20). At doses of vitamin B2 of 2.5, 5, 10, and 20 mg/kg of body weight, survival levels were 35% (7 of 20), 65% (13 of 20 [P < 0.05]), 90% (18 of 20 [P < 0.05]), and 95% (19 of 20 [P < 0.05]), respectively (Fig. (Fig.1A).1A). Moreover, treatment with vitamin B2 at 20 mg/kg 6 h after LPS injection not only lowered levels of excessive plasma proinflammatory cytokines, including tumor necrosis factor alpha (Fig. (Fig.2A),2A), interleukin-1 beta (IL-1β) (Fig. (Fig.2B),2B), IL-6 (Fig. (Fig.2C),2C), gamma interferon (Fig. (Fig.2D),2D), monocyte chemotactic protein 1 (Fig. (Fig.2E),2E), and macrophage inflammatory protein 2 (Fig. (Fig.2F),2F), but also decreased NO levels (Fig. (Fig.2G2G)"

    "...At 6 h after injection of SEB-d-galactosamine, vitamin B2 was administered with a bolus injection. The survival rate of the control group was 0% (0 of 30). The survival rates of the groups treated with vitamin B2 at 2.5, 5, 10, and 20 mg/kg were 3% (1 of 30), 10% (3 of 30), 27% (8 of 30 [P < 0.05]), and 43% (13 of 30 [P < 0.05]), respectively (Fig. (Fig.1B1B). Vitamin B2 was given 24 h before E. coli inoculation (2.07 × 108 CFU). The survival rate of the control group was 8% (2 of 25). The survival rates of the groups treated with vitamin B2 at 2.5, 5, 10, and 20 mg/kg were 20% (5 of 25), 60% (15 of 25 [P < 0.05]), 76% (19 of 25 [P < 0.05]), and 88% (22 of 25 [P < 0.05]), respectively (Fig. (Fig.1C).1C). In addition, vitamin B2 administered at 20 mg/kg 24 h before E. coli inoculation significantly reduced levels of the bacteria in the blood (Fig. (Fig.33)"

    "...Vitamin B2 was given with a bolus injection immediately and 1 and 2 days after S. aureus inoculation (1.69 × 108 CFU). The survival rate of the control group was 0% (0 of 30). The survival rates of the groups treated with vitamin B2 at 2.5, 5, 10, and 20 mg/kg were 0% (0 of 29), 30% (9 of 30 [P < 0.05]), 53% (16 of 30 [P < 0.05]), and 50% (15 of 30 [P < 0.05]), respectively (Fig. (Fig.1D1D). Furthermore, we investigated the therapeutic effect of vitamin B2 in long-term intravenous treatment by infusion using an infusion pump (Natsume, Tokyo, Japan). Infusion of vitamin B2 for 6 h (E. coli infection) or 12 h (S. aureus infection) was begun 1 h after inoculation with bacteria. In the E. coli infection experiments, the survival rate of the control group was 0% (0 of 30). Survival rates of the groups treated with vitamin B2 at 5, 10, 20, and 40 mg/kg/6 h were 20% (2 of 10), 30% (3 of 10 [P < 0.05]), 55% (11 of 20 [P < 0.05]), and 70% (7 of 10 [P < 0.05]), respectively (Fig. (Fig.4A).4A). In the S. aureus infection experiments, the survival rate of the control group was 0% (0 of 10) and the survival rates of the groups treated with vitamin B2 at 20, 40, and 80 mg/kg/12 h were 20% (2 of 10), 50% (5 of 10 [P < 0.05]), and 70% (7 of 10 [P < 0.05]), respectively (Fig. (Fig.4B4B)."

    "...Infusion of vitamin B2 with or without APC for 6 h was commenced 6 h after LPS or SEB injection. The survival rate of the control group was 0% (0 of 10) for LPS-treated mice. The survival rates of the groups treated with vitamin B2 (10 mg/kg/6 h), APC (75 units/kg/6 h), and vitamin B2 plus APC were 50% (5 of 10 [P < 0.05]), 30% (3 of 10), and 90% (9 of 10 [P < 0.05]), respectively (Fig. (Fig.4C).4C). In SEB-treated mice, the survival rates of the control group and the groups treated with vitamin B2 (20 mg/kg/6 h), APC (300 units/kg/6 h), and vitamin B2 plus APC were 0% (0 of 10), 60% (6 of 10 [P < 0.05]), 40% (4 of 10), and 90% (9 of 10 [P < 0.05]), respectively (Fig. (Fig.4D4D)."

    "...Treatment with vitamin B2 lowered the levels of cytokines (4, 10, 11) and NO (12) that are implicated in the pathogenesis of sepsis and likely enhanced the eradication of bacteria. Thus, vitamin B2 may provide an approach for immunotherapy in the treatment of many inflammatory diseases (including systemic inflammatory response syndrome, cachexia, chronic rheumatism, and nephritis) without excessive suppression of the host defense system. Simultaneous administration of vitamin B2 with APC reduced the mortality of endotoxin- and exotoxin-induced shock, suggesting that therapy with vitamin B2 combined with agents having other properties could be an effective approach to treat sepsis. In conclusion, treatment with highly purified vitamin B2 (riboflavin 5′-sodium phosphate; purity > 97%) reduced levels of mortality in mice with septic shock and may be useful for the treatment of patients with sepsis."
     
  2. schultz

    schultz Member

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    This is amazing! Thanks for sharing.
     
  3. Tarmander

    Tarmander Member

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    Nice post. I actually was just thinking about this, we must be on the same wavelength. I have had some issues with restless leg, which I attributed to endotoxin. My basic protocol, from reading your previous posts, was 1mg MB, 400mg Riboflavin, and a "crap ton" of coconut oil. Works FANTASTICALLY.

    I have had trouble sourcing R5P by itself. I found it in capsules, but the R5P is basically in such a small amount, you are taking a bunch of fillers (10mg R5P, 990mg cellulose bollix). Despite this, I tried the capsule version (Douglas Labs I believe), but I got a sore throat, and bloating which I associate with endotoxin. I switched to a plain Riboflavin powder and these issues went away. So what I really need is a powder version of R5P.
     
  4. Amazoniac

    Amazoniac Member

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    Thank you for this great post. B vits are dear to your heart, aren't they?
     
  5. milk_lover

    milk_lover Member

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    I have a role for myself.. taking the small B vitamins (B1,B2,B3) daily and taking the large B vitamins (B6, B7) biweekly. This has worked best for me. God I get excited when I see a new post by haidut, I always learn new stuff. Thanks for all your effort, man!
     
  6. DaveFoster

    DaveFoster Member

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    Why not B7 daily as well?
     
  7. Elephanto

    Elephanto Member

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    B2 is one of the only vitamin consistently correlated with prostate cancer. I find it interesting that it's a coenzyme for Mao-a since I already posted a study showing mao-a to promote prostate cancer growth, but I didn't know about the link with B2.

    One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. - PubMed - NCBI
    Choline and B2 are significantly associated with prostate cancer

    Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration. - PubMed - NCBI
    High dose B2 promotes lung cancer
     
  8. jyb

    jyb Member

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    Anyone actually tried B2? I never really noticed much from supplementing the B vits (except possibly B3), but I haven't tried them all.
     
  9. lindsay

    lindsay Member

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    I bought a B2 supplement lately. It looks like Turmeric powder. I have heard from a friend, however, that she tried supplementing B2 last summer because she heard it helps with deterring mosquitos. It gave her a terrible migraine and nausea. So I think taking small doses is super important. Didn't RP say something in one of his interviews like 10 to 15 mg per day for someone who is deficient?
     
  10. 800mRepeats

    800mRepeats Member

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    Is Pure Bulk an option for you?
    Riboflavin 5 Phosphate - Pure Bulk Supplements
     
  11. lindsay

    lindsay Member

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    I have taken it in small doses and in my espresso (which apparently has a decent amount of Riboflavin and a lot more Niacin than regular coffee - probably one of the reasons it's good for the liver). I haven't really noticed much of a difference, but I'm also not super fond of MB, though I've only used a drop of it when my tummy is upset. Ginger oil is way more powerful IMO. In fact, I was trying to find studies today because I read in quite a few places that ginger inhibits serotonin uptake in the gut (aka, serotonin "receptors"), which is why it's so powerful against nausea. I love the stuff.
     
  12. jaa

    jaa Member

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    Damn Purebulk's R5P is not cheap. Close to $0.50/gram!
     
  13. moss

    moss Member

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    Supplements aside - mushrooms are a great source of B2 as well.
     
  14. Tarmander

    Tarmander Member

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  15. ecstatichamster

    ecstatichamster Member

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    But normally you don't need more than 10 milligrams or so. And if u are sick then the cost isn't that important because 50 cents a gram would mean it costs a few bucks to recover instead of costly and potentially harmful antibiotics
     
  16. Giraffe

    Giraffe Member

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    The cell culture study found that "Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines." This is 5,000 times the highest concentration they found is the blood plasma in that observational human study.

    Regarding that observational study, it is very mysterious how they came to their conclusions. I couldn't find a single hint.
     
  17. robknob

    robknob Member

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    Cronometer has egg whites at about 1mg riboflavin per cup, and with dairy I can get about 6-7 mg from food a day. The b2 supplement I have doesn't have any noticeable effect on me, and it seems to pass through my urine within about 18 hours. I don't think it gets absorbed at all...
     
  18. jaa

    jaa Member

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    True. My internal calculator wasn't working well last night :D.
     
  19. milk_lover

    milk_lover Member

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    I tend to take my B vitamins with lunch that barely has enough sugar (coke or two with a lot of meat, which might not be that healthy) and If I take huge amounts of biotin (5 mg) I get hypoglycemia symptoms. It's very powerful in reducing blood sugar. When I had the 300 mcg pills, I was taking biotin almost everyday.
     
  20. OP
    haidut

    haidut Member

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    Yep, I think for people without access to thyroid supplement the B vitamins is one of the few safe alternatives. Given the recent blockbuster performance of biotin in human trials of MS it would not be long before FDA requires a prescription for all of them.
     
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