Vitamin B2 (riboflavin) Reduces Lipofuscin, May Extend Lifespan

haidut

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There are few reliable treatments of the so-called "age spots" officially known as lipofuscin. Ray has written about the role of iron, PUFA and estrogen in the formation of this skin pigment and has suggested that vitamin E may be one possible treatment. Now we can add vitamin B2 to the list of possible treatments. Interestingly, vitamin B2 also increased levels of catalase, which is one of the enzyme consistently found elevated in centenarians.

Anti-Aging Effect of Riboflavin Via Endogenous Antioxidant in Fruit fly Drosophila Melanogaster. - PubMed - NCBI
"... MEASUREMENTS: The activity of copper-zinc-containing superoxide dismutase (SOD1), manganese containing SOD (SOD2) and catalase (CAT) and lipofuscin (LF) content were determined. RESULTS:
Riboflavin significantly prolonged the lifespan (Log rank χ2=16.677, P<0.001) and increased the reproductive capacity (P<0.01 for day 15; P<0.05 for day 30) of fruit flies by lifelong supplement. The survival time of fruit flies damaged by H2O2 was significantly prolonged (Log rank χ2=15.886, P<0.001), the activity of SOD1 (P<0.01) and CAT (P<0.01) was enhanced, and the accumulation of LF (P<0.01) was inhibited by riboflavin supplement. CONCLUSION: Riboflavin prolonged the lifespan and increased the reproduction of fruit flies through anti-oxidative stress pathway involving enhancing the activity of SOD1 and CAT and inhibiting LF accumulation. Riboflavin deserves more attention for slowing human aging."
 

schultz

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This is incredibly important. It doesn't take long to realize, once you start researching lipofuscin in depth, that is one of the primary, if not the primary, drivers of aging. Take this sentence from the study...

"LF accumulation has been related to age-dependent mortality (31), and thus is deemed to be a hallmark of aging (32)."

Lipofuscin can inhibit the proteasome. It's easy to understand why this would be bad for the health and lifespan of organisms.

I'm of the opinion that the Hayflick limit is silly. Lipofuscin in the cell seems to be one of the reasons a cell becomes senescent, yet in many papers it will often say that lipofuscin accumulates in cells that are already senescent. Maybe the cell becomes senescent because of the lipofuscin?

Haidut, maybe I am reading incorrectly, but the paper implies that riboflavin prevents the build-up of lipofuscin rather than the removal from the cell. Is it safe to say that it is preventative rather than curative? Or is there some evidence that riboflavin can help remove lipofuscin that has already deposited itself?

The reason I ask is because I see sentences like the one below in papers...

"Lipofuscin is a non degradable aggregate of oxidized proteins, lipids and metals which accumulates inside the lysosomes of cells that do not replicate."

On the other hand, Ray has mentioned that topical vitamin E might actually help remove lipofuscin (not only prevent it in the first place).

 
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haidut

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This is incredibly important. It doesn't take long to realize, once you start researching lipofuscin in depth, that is one of the primary, if not the primary, drivers of aging. Take this sentence from the study...

"LF accumulation has been related to age-dependent mortality (31), and thus is deemed to be a hallmark of aging (32)."

Lipofuscin can inhibit the proteasome. It's easy to understand why this would be bad for the health and lifespan of organisms.

I'm of the opinion that the Hayflick limit is silly. Lipofuscin in the cell seems to be one of the reasons a cell becomes senescent, yet in many papers it will often say that lipofuscin accumulates in cells that are already senescent. Maybe the cell becomes senescent because of the lipofuscin?

Haidut, maybe I am reading incorrectly, but the paper implies that riboflavin prevents the build-up of lipofuscin rather than the removal from the cell. Is it safe to say that it is preventative rather than curative? Or is there some evidence that riboflavin can help remove lipofuscin that has already deposited itself?

The reason I ask is because I see sentences like the one below in papers...

"Lipofuscin is a non degradable aggregate of oxidized proteins, lipids and metals which accumulates inside the lysosomes of cells that do not replicate."

On the other hand, Ray has mentioned that topical vitamin E might actually help remove lipofuscin (not only prevent it in the first place).

They did not check if riboflavin reduced already established lipofuscin, so we can't really say one way or another. I will send them an email. Btw, in the same study they found something that indicated riboflavin may be anti-eestrogenic or even androgenic.
"...Interestingly, except for the total amount of offspring, riboflavin supplement increased the male proportion of the offspring of fruit flies. No more information about this effect could be obtained till now."

This certainly matches well with the requirements of B1 and B2 in order for the liver to be able to eliminate estrogen but it could also mean riboflavin may act on steroid synthesis or receptors to increase androgenic tone. Aspirin administration, as well as low doses DHEA have been shown to increase proportion of make offspring in humans.
Finally, riboflavin and LP emit/reflect the same frequency of light (500nm - 540nm).
Imaging Living Cells

Even more interestingly, studies show that amount of LP accumulation is a biomarker of immune system (dys)function, and riboflavin potentiates immune system response.
Environmental Pollution

So, riboflavin and LP seem have opposing functions in all organisms tested so far and I would not be surprised if riboflavin can actually remove already accumulated LP. The dose used in the fly study of the original thread used a dose that in humans would correspond to 240mg daily (assuming 2kg average daily food intake). That is not much at all and is without any species conversion factors, which undoubtedly exists since the flies have much faster metabolism than us. My guess is the scaling factor would be about 1/10, so a dose of 20mg - 25mg daily in humans should replicate the design of the study.
 

schultz

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They did not check if riboflavin reduced already established lipofuscin, so we can't really say one way or another. I will send them an email. Btw, in the same study they found something that indicated riboflavin may be anti-eestrogenic or even androgenic.
"...Interestingly, except for the total amount of offspring, riboflavin supplement increased the male proportion of the offspring of fruit flies. No more information about this effect could be obtained till now."

This certainly matches well with the requirements of B1 and B2 in order for the liver to be able to eliminate estrogen but it could also mean riboflavin may act on steroid synthesis or receptors to increase androgenic tone. Aspirin administration, as well as low doses DHEA have been shown to increase proportion of make offspring in humans.
Finally, riboflavin and LP emit/reflect the same frequency of light (500nm - 540nm).
Imaging Living Cells

Even more interestingly, studies show that amount of LP accumulation is a biomarker of immune system (dys)function, and riboflavin potentiates immune system response.
Environmental Pollution

So, riboflavin and LP seem have opposing functions in all organisms tested so far and I would not be surprised if riboflavin can actually remove already accumulated LP. The dose used in the fly study of the original thread used a dose that in humans would correspond to 240mg daily (assuming 2kg average daily food intake). That is not much at all and is without any species conversion factors, which undoubtedly exists since the flies have much faster metabolism than us. My guess is the scaling factor would be about 1/10, so a dose of 20mg - 25mg daily in humans should replicate the design of the study.

Thanks for explaining all that.

I did notice that part about the males, but didn't understand the relevance so I put it in the back of my mind.

In the Ray Peat e-mail advice depository thread, I noticed someone (Dan Wich posted it, but he didn't say he was the one asking the question) asked Ray about creatine and Ray sent him a few studies. One of the studies said that creatine can extend life by inhibiting lipofuscin.

Amino Acids. 2011 May;40(5):1297-303.
Creatine in mouse models of neurodegeneration and aging.

A snippet of the abstract says this...

"The median healthy life span of creatine-fed mice was 9% higher than in their control littermates, and they performed significantly better in neurobehavioral tests. In brains of creatine-treated mice, there was a trend toward a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin."

I was a little unsure how creatine would be protective (the energy system maybe?).

Anyway, I just thought I'd mention it since the thread is partially about lipofuscin (even though it's off topic from B2).

I'm also noticing another thread of yours below in the "Similar Threads" list. Vitamin B2 is an endotoxin LPS / TLR4 antagonist. I have a newfound respect for B2! I have a question regarding this but will ask it on the other thread.
 

haidut

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Thanks for explaining all that.

I did notice that part about the males, but didn't understand the relevance so I put it in the back of my mind.

In the Ray Peat e-mail advice depository thread, I noticed someone (Dan Wich posted it, but he didn't say he was the one asking the question) asked Ray about creatine and Ray sent him a few studies. One of the studies said that creatine can extend life by inhibiting lipofuscin.

Amino Acids. 2011 May;40(5):1297-303.
Creatine in mouse models of neurodegeneration and aging.

A snippet of the abstract says this...

"The median healthy life span of creatine-fed mice was 9% higher than in their control littermates, and they performed significantly better in neurobehavioral tests. In brains of creatine-treated mice, there was a trend toward a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin."

I was a little unsure how creatine would be protective (the energy system maybe?).

Anyway, I just thought I'd mention it since the thread is partially about lipofuscin (even though it's off topic from B2).

I'm also noticing another thread of yours below in the "Similar Threads" list. Vitamin B2 is an endotoxin LPS / TLR4 antagonist. I have a newfound respect for B2! I have a question regarding this but will ask it on the other thread.

I think creatine has multiple life extension mechanisms. Did not know about its ability to reduce LP but its ability to lower serotonin would definitely make it life extending considering the studied on serotonin antagonists I posted showing up to 40% extension with mianserin and cyproheptadine. See below.
Dopamine, Serotonine, Creatine: Creatine Supplementation Modulates Post-Exercise Neurotransmitter Levels in Man - SuppVersity: Nutrition and Exercise Science for Everyone
 

Makaveli

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@haidut have you considered releasing a pure riboflavin supplement? I remember reading here recently that there are no good pure riboflavin supplements out there.
 

Snowman

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@haidut Do you have any advice on how to tolerate taking riboflavin supplements without getting stiffness, back pain, and sciatica? I am deficient in riboflavin, have tolerated it just fine years ago, but cannot tolerate it now and have no idea why. I am not good at navigating forums, so if the answer is elsewhere I'd much appreciate a link or help finding it.
 

haidut

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@haidut have you considered releasing a pure riboflavin supplement? I remember reading here recently that there are no good pure riboflavin supplements out there.

The riboflavin in Energin is pretty pure and it is the activated kind R5P, so it is equivalent to a 10-fold higher dose of regular riboflavin.
 

haidut

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@haidut Do you have any advice on how to tolerate taking riboflavin supplements without getting stiffness, back pain, and sciatica? I am deficient in riboflavin, have tolerated it just fine years ago, but cannot tolerate it now and have no idea why. I am not good at navigating forums, so if the answer is elsewhere I'd much appreciate a link or help finding it.

I would take riboflavin as a B complex supplement. Isolates B2 supplementation seems to cause issues for some people and when taken in combination with the other B vitamins the issues often disappear.
 

Mary Pruter

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There are few reliable treatments of the so-called "age spots" officially known as lipofuscin. Ray has written about the role of iron, PUFA and estrogen in the formation of this skin pigment and has suggested that vitamin E may be one possible treatment. Now we can add vitamin B2 to the list of possible treatments. Interestingly, vitamin B2 also increased levels of catalase, which is one of the enzyme consistently found elevated in centenarians.

Anti-Aging Effect of Riboflavin Via Endogenous Antioxidant in Fruit fly Drosophila Melanogaster. - PubMed - NCBI
"... MEASUREMENTS: The activity of copper-zinc-containing superoxide dismutase (SOD1), manganese containing SOD (SOD2) and catalase (CAT) and lipofuscin (LF) content were determined. RESULTS:
Riboflavin significantly prolonged the lifespan (Log rank χ2=16.677, P<0.001) and increased the reproductive capacity (P<0.01 for day 15; P<0.05 for day 30) of fruit flies by lifelong supplement. The survival time of fruit flies damaged by H2O2 was significantly prolonged (Log rank χ2=15.886, P<0.001), the activity of SOD1 (P<0.01) and CAT (P<0.01) was enhanced, and the accumulation of LF (P<0.01) was inhibited by riboflavin supplement. CONCLUSION: Riboflavin prolonged the lifespan and increased the reproduction of fruit flies through anti-oxidative stress pathway involving enhancing the activity of SOD1 and CAT and inhibiting LF accumulation. Riboflavin deserves more attention for slowing human aging."
Thank you, Haidut!
 

Pointless

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@haidut Do you have any advice on how to tolerate taking riboflavin supplements without getting stiffness, back pain, and sciatica? I am deficient in riboflavin, have tolerated it just fine years ago, but cannot tolerate it now and have no idea why. I am not good at navigating forums, so if the answer is elsewhere I'd much appreciate a link or help finding it.

It could also be an allergy to some of the impurities like Peat has talked about.
 

Snowman

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I would take riboflavin as a B complex supplement. Isolates B2 supplementation seems to cause issues for some people and when taken in combination with the other B vitamins the issues often disappear.
I forgot to mention I have same problems if any B2 or R5P is within in a b-complex. I may be low in several vitamins and minerals, malabsorption, chronic illness, many food allergies. Not sure what else could be affecting B2 intoelrance. I will give the b complex another try. Thank you Haidut.
 

Snowman

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It could also be an allergy to some of the impurities like Peat has talked about.
Interesteing idea. I've tried pure bulk riboflavin and flavin mononucleotide (R5P) without fillers and had same reaction, but still could be an impurity in their source. Any luck with other brands of pure powdered supplements?
 

chispas

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I would take riboflavin as a B complex supplement. Isolates B2 supplementation seems to cause issues for some people and when taken in combination with the other B vitamins the issues often disappear.

Any evidence that B2 aids weightloss?

My partner started taking it everyday in the hope it would prevent migraine. She took it for a year and all it led to was weight loss and hyperthyroidism.
 
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Any evidence that B2 aids weightloss?

My partner started taking it everyday in the hope it would prevent migraine. She took it for a year and all it led to was weight loss and hyperthyroidism.

Drag. I would be delighted if I had weight loss and hyperthyroidism.

Do you know her dosages?
 

milk_lover

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I wish I could react to B2 positively like your wife! It always gives me allergy symptoms..
 

Jon

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Thanks for explaining all that.

I did notice that part about the males, but didn't understand the relevance so I put it in the back of my mind.

In the Ray Peat e-mail advice depository thread, I noticed someone (Dan Wich posted it, but he didn't say he was the one asking the question) asked Ray about creatine and Ray sent him a few studies. One of the studies said that creatine can extend life by inhibiting lipofuscin.

Amino Acids. 2011 May;40(5):1297-303.
Creatine in mouse models of neurodegeneration and aging.

A snippet of the abstract says this...

"The median healthy life span of creatine-fed mice was 9% higher than in their control littermates, and they performed significantly better in neurobehavioral tests. In brains of creatine-treated mice, there was a trend toward a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin."

I was a little unsure how creatine would be protective (the energy system maybe?).

Anyway, I just thought I'd mention it since the thread is partially about lipofuscin (even though it's off topic from B2).

I'm also noticing another thread of yours below in the "Similar Threads" list. Vitamin B2 is an endotoxin LPS / TLR4 antagonist. I have a newfound respect for B2! I have a question regarding this but will ask it on the other thread.
 

Mufasa

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@haidut My girlfriend is going to try energin applied topically at bight on a brown aging spot on her forehead. She also uses progesterone topically dissolved in oil in the last two weeks of her cycle, do you think it can mix? Or maybe progesterone in the morning and energin in the evening?

I saw that Ray Peat mentioned that alcohol may help getting rid of lipofuscin, so it may be good that is is in energin.
 
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