#82

Impact of Cyanocobalamin and Methylcobalamin on Inflammatory Bowel Disease and the Intestinal Microbiota Composition 2018

Chinese paper, but might be interesting to some people here:

Patients with inflammatory bowel disease (IBD) are usually advised to supplement various types of vitamin B12, because vitamin B12 is generally absorbed in the colon. Thus, in the current study, the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on IBD symptoms will be investigated. […] a high concentration of CNCBL but not MECBL supplementation obviously aggravated IBD.

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#83

On what basis is methylcobalamin or hydroxocobalamin considered better for kidney function than cyanocobalamin?

I clincked around on the link, and it got me to another page bringing up precisely this point:

While Dr. Spence’s recommendation of methylcobalamin or hydroxycobalamin makes sense based upon current available clinical data, it is noteworthy that no clinical studies have directly compared these two compounds vs. cyanocobalamin for stroke prevention in individuals with normal and/or impaired renal function.

https://www.journal-of-hepatology.eu/article/S0168-8278(22)03140-3/fulltext

Is there any clinical trial comparing methylcobalamin with cyanocobalamin? Or at least a clinical trial showing no worsening in kidney function of methylcobalamin?

#84

I forgot, I posted that previously.

I’ve already posted some. For instance: A comprehensive review and meta-regression analysis of randomized controlled trials examining the impact of vitamin B12 supplementation on homocysteine levels 2023

Furthermore, the effect of B12 supplementation in the form of hydroxocobalamin on the reduction of Hcy level was greater compared with other forms. […] On the other hand, the effect of methylcobalamin was greater than that of cyanocobalamin.

There’s also this ongoing trial: ClinicalTrials.gov

#85

Is it comparing kidney function?

For all we know, hydroxocobalamin or methylcobalamin might harm kidneys the same way, and thus no use to switch to methylcobalamin.

#86

Ah, sorry on kidney function; as said, I think I posted before links saying that methylcobalamin was better for kidneys.

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#87

Actually, it seems that no trials specifically compared the effects of methylcobalamin vs. cyanocobalamin vs. hydroxocobalamin on kidney function. Most recommendations are based on the clinical observation of kidney function decline with cyanocobalamin and theoretical advantages of other forms: cyanocobalamin contains a cyanide molecule, which, although present in very small amounts, needs to be detoxified and eliminated by the kidneys. Methylcobalamin and hydroxocobalamin do not contain a cyanide group like cyanocobalamin, thus eliminating the concern of cyanide accumulation.

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#88

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A short study in adolescents showed improvement in kidney function with cyanocobalamin (graph is the longer study).

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The average daily intake of cyanide barely moves with 1000 mcg cyanocobalamin a day (even though it’s recommended for most adults to only take 2000 mcg one time a week).

I wonder if cyanocobalamin actually harms kidney function if it’s not already impaired.
If it’s the cyanide, such a small difference in intake probably doesn’t affect normal kidney function, it’s probably a very safe supplement.

#89

Do you think an SGLT2I would eliminate the issue with cyanocobalamin?

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#90

I don’t know. I take methylcobalamin, seems like a no brainer.

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#91

Hi @adssx - can you point to where you found the eGFR vs. age graphs for men and women in your recent post?

#92

Do a reverse Google Image search as it was just a random image to illustrate the decline.

[EDIT: back on my computer, here it is: Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study 2021]

However I posted a more accurate chart in another thread (I’m on my phone now, not easy to find it…).

[EDIT: Actually I haven’t and I found it hard to find good sources of real GFR and estimated GFR (which one? eGFRcr? eGFRcr-cys?] by age]

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#93

I would like to test my homocysteine level but it isn’t take in charge by the social healthcare in France. And it is something like 55€. Pretty expensive and and don’t see the point to test it because I supplement with b9, b12 and TMG for years.
Somehow doctors in France think it is a useless test to do.

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#94

Thanks a lot @adssx - appreciated

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#95

Homocysteine acts as a “chain-breaker” for connective tissue proteins like collagen and elastin It does this through a “cyclization” reaction where it spontaneously forms a ring structure, disconnecting the amino acid chain It can either be incorporated into proteins in place of cysteine, or bind sulfur-containing amino acids through disulfide S-S bonds Both create disruption in structure leading to aging


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7:30 PM · Jul 26, 2024

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#96

Homocysteine mimics glutamate, activating NMDA receptors and promoting calcium influx both into cells and into the brain. Calcium influx is a key component of the “universal stress response” in all parts of the organism. Homocysteine also acts as a negative allosteric modulator of D2 dopamine receptors in the brain.

Beyond this, homocysteine can form a pentagonal ring structure known as a homocysteine thialactone. Homocysteine replaces cysteine in various proteins, and can cause proteins to destabilize by forming a thialactone, cleaving the structure. Most circulating homocysteine forms disulfide bonds with other sulfur containing amino acid sites like cysteine, and this protein-bound homocysteine can disrupt the structural proteins collagen and elastin.

Homocysteine is also associated with clotting disorders, and this plays a role in its association with aging and cardiovascular disease. The “zeta potential” in blood cells refers to the layer of negative charge carried by red blood cells, which buffers them to prevent clotting and binding to the vascular endothelium. Sulfate ions are the main negative ions that line both red blood cells and the proteoglycan lining of blood vessels (see the work of Seneff et al. at MIT). Homocysteine diminishes zeta potential through damage to the proteoglycan layer (8).

Homocysteine may also alter healing and tissue inflammatory response by binding to fibronectin

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#97

Serum Homocysteine Levels and All-Cause and Cause-Specific Mortality in Korean Adult Men: A
Cohort Study 2024

Compared with the reference category (Q2, 8.8–9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L).

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Interesting U-curve here. As a reminder, as far as I know, Mendelian randomization studies have never found that homocysteine was causally associated with all-cause or cause-specific mortality. And RCTs have never found significant benefits of homocysteine-lowering interventions.

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#98

I have the worst variant of MTHFR, but strangely, without doing anything special my homocysteine has never been high. However for the past few months I’ve been taking TMG 1g/day for exercise, and I think my choline intake is not super low (egg x3 week, cruciferous veg.). My homocysteine measured 3 weeks ago was 7 mcmol/L. I keep reading about how dire my MTHFR is, but can never figure out what I should be looking for to see if I have some effects. My serum B12 is 863 pg/mL. I don’t supplement with B12, other than the cyanocobalamin 6mcg 4 times a week in my B-vitamin pill (salmon or sardine 1-2 tmes a week).

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#99

If that is true, lowering Homocystine from 12 to 8 doesn’t seem to move the needle in terms of health. I read somewhere that Hcy was related to RDW and that really moves the needle, maybe we can use RDW instead as our goal.

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#100

I tested mine at 15 µmol/L :see_no_evil:

I’m adding Methyl-B12 & Folate and doing some more testing. I thought 2 mg cyanocobalamin a week would be good.

I’m starting to see the value in doing blood tests.

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#101

There’s zero evidence of benefits from homocysteine-lowering therapies. Take methyl-B12 & folate if yours are low, but I would not take them for homocysteine-lowering per se.

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