B12 May Be Detrimental?

[EmsXen33]

Hi, I'm new to posting here but have been following this group for awhile and find it to be a very helpful and supportive community. I have a question about a research study published March 26, 2024, in a journal called Cell Reports (I did a quick search and learned that Cell Reports is a legitimate and reputable journal). I'm not sure how I found the study. I am not a scientist or medical professional.

In the ten years since I was diagnosed with PD, I have been under instruction from the medical community to supplement with B12 - the more the better. As I understand this study, it suggests that B12 may actually worsen PD symptoms. Does anyone know anything about this or can comment on this study?

Link is here: cell.com/cell-reports/fullt...

And here is the explanation of the study's conclusions after I ran the study through Scholarcy:

"Conclusions

The study concludes that propionate is a key metabolite that modulates neurodegeneration in a Caenorhabditis elegans model of Parkinson's disease through bidirectional regulation between the intestine and neurons.

The study concludes that vitamin B12 and α-synuclein aggregation contribute to neurodegeneration through similar metabolic changes and transcriptional reprogramming, and that restoring propionate levels may be a potential therapeutic strategy for Parkinson's disease.

The study concludes that SCFAs, particularly propionate, are promising candidates for the metabolic rescue of Parkinson's disease, and that vitamin B12 has a detrimental effect on neurodegeneration in C. elegans models of Parkinson's disease.

The study concludes that vitamin B12 promotes neurodegeneration in C. elegans models of Parkinson's disease, and that depletion of dietary vitamin B12 may be a potential therapeutic strategy for the treatment of Parkinson's disease.

The study concludes that vitamin B12 does not alter neuronal a-syn aggregation, but its effects on neurodegeneration are downstream of protein aggregation. The study also suggests that propionate may be a potential therapeutic target for neurodegenerative diseases.

The study concludes that propionate has a neuroprotective effect against a-syn-induced neurodegeneration in C. elegans and mammalian neurons, and that this effect is mediated by the activation of metabolic genes in the intestine and the improvement of mitochondrial functions."

[park_bear]

The key point is right here:

"Both depletion of dietary vitamin B12, which induces propionate breakdown, and propionate supplementation suppress neurodegeneration and reverse PD-associated transcriptomic aberrations."

Anyone who understands what B12 does will understand that intentionally depleting B12 is absolutely insane. This paper says that propionate supplementation is as good as depleting B12 in the matter discussed, so which alternative to take is clear (if we accept the validity of this research on flatworms applying to human PD).

[Gallowglass]

I dont understand the science of this, but on practical level I’ve noticed that b12 works better for me when taken twice a week.

[MPPD in reply to Gallowglass]

How much B12 do you take each week?

[SAGoodman]

I take B12 daily

[barrie1757]

And there are studies indicating that it is beneficial.

[qazwsx11]

Vitamin b12 comes in several forms. Make sure to use Metyl cobalamin. Many of us have a defective MTHFR gene which is responsible for metabolizing B12. So taking lots of the wrong B12 will not always help.

IMO once the damage to the dopaniergic system happens B12 supplements can only help reducing inflammation but not reverse the damage.

Look for 1-Carbon cycle for details

[Mellaji in reply to qazwsx11]

It would be an interesting study to see how many of those with Parkinson’s have MTHFR. I do also.

[qazwsx11 in reply to Mellaji]

Yes, also COMPT and SYNC

[Esperanto]

See the previous discussions in the post of Farooqji 10 months ago:

healthunlocked.com/cure-par...

[chartist]

Their theory is based on a roundworm model of PD as mentioned here :

' The study concludes that vitamin B12 promotes neurodegeneration in C. elegans models of Parkinson's disease, and that depletion of dietary vitamin B12 may be a potential therapeutic strategy for the treatment of Parkinson's disease. '

Imo, it is a poor model for human PD and is not likely to translate directly to humans with PD who naturally have lower levels of B12. Lower levels of B12 in humans in general is not healthful and similarly in C. elegans.

The following USFC article discussing vitamin B12 in humans with PD tends to confirm that their conclusion regarding the C. elegans PD model, as would relate to actual people with PD is very likely incorrect :

ucsf.edu/news/2018/03/40999....

Here are two very relevant article quotes :

' A study of patients with early Parkinson’s disease found that groups with lower levels of vitamin B12 faced on average a more rapid acceleration of both motor and cognitive symptoms, which slowed in some cases after taking a daily multivitamin. '

' “Our findings demonstrate that low B12 levels are associated with greater walking and balance problems, possibly due to the known effect of B12 deficiency on the central and peripheral nervous systems,” said Christine. “Alternatively, low B12 may have a direct effect on the progression of Parkinson’s disease, or it may be a marker of an unknown associated factor, perhaps correlating with another aspect of the disease or nutritional status.” '

To add insult to injury, low B12 levels can also be detrimental to the roundworm.

Sometimes you have to weed out studies such as these that were likely done for the sole purpose of getting funding to do a study using a C. elegans PD model with no actual useful purpose or value for the PD community, being as low vitamin B12 levels, have already been established as detrimental for the health of people with and without PD, who often times already have low B12 levels. In other words they just wasted valuable PD research dollars on a worthless study. Sorry, I'm not feeling very charitable today and that was as nicely as I could say what a waste their study was.

Art

[EmsXen33]

Thanks for these comments. I apologize for asking a question that was asked and discussed ten months ago. I recognize that C. elegans worm data likely doesn’t translate to human data, as Art and Park Bear have repeatedly emphasized. And I also recognize that this study may be one of those, as Art points out, that was done to generate funding rather than to advance useful patient-centered research. That’s especially so because it is written so poorly and makes no attempt to situate itself in relation to the gobs of other research demonstrating the importance of B12 supplementation for people with PD.

All I have ever heard since diagnosis is to take B12 – both general recommendations from neurologists and primary care doctors, along with a more specific recommendation from a functional medicine doctor that no amount of B12 is too much. (I do take the methylcobalamin form of B12 and I have the MTHFR gene variant - I’m positive for both one copy of the C677T variant and one copy of the A1298C variant.) Although my plasma B12 level is high, I was told “that just shows you’re taking it, not that your body is processing it.” Homocysteine was key, I was told, and I was able to get my very high homocysteine level to within normal levels through taking more B vitamins.

But Esperanto’s discussion of balance in the original thread has me thinking that maybe I should be more careful here: “It is once again a confirmation that balance is key when it comes to B vitamins and that we should be cautious with high doses. Although doubts have been raised before about high doses of B12 linked to increased mortality risk in cardiovascular diseases. However this association with propionate is remarkable and the research itself is very interesting and promising!”

I plan on paying more regular and careful attention to my B vitamin levels and also possibly, maybe, after further research, look into adding propionic acid to my stack.

Thanks everyone! Cheers, and Happy Holidays!

[chartist in reply to EmsXen33]

Taking the fiber supplement Inulin + FOS such as this increases propionate levels and increases health promoting bacteria in the gut :

amazon.com/Jerusalem-Artich...

The following mid 2023 link discusses how inulin increases SCFAs, butyrate, acetate and especially propionate:

pmc.ncbi.nlm.nih.gov/articl...

Here is a relevant quote from the link :

' Recently, several studies have found that dietary supplementation of inulin can improve metabolic function and regulate intestinal immunity. Inulin is fermented in the colon by the gut microbiota and a series of metabolites is generated. Among these metabolites, short-chain fatty acids provide energy to intestinal epithelial cells and participate in regulating the differentiation of immune cells. Inulin and its intestinal metabolites contribute to host immunity. This review summarizes the effect of inulin and its metabolites on intestinal immunity, and the underlying mechanisms of inulin in preventing diseases such as type 2 diabetes mellitus, inflammatory bowel disease, chronic kidney disease, and certain cancer types. '

Art