#69

Can possibly raise LDL when more than 4g a day are used.

1 Like
#70

I haven’t looked at it. I don’t know what kind of good content can be behind a paywall on this topic. I mean: what more than the academic papers already published? Looking at these, I haven’t found evidence of benefits for Hcy-lowering therapies (besides some association studies, but by that reasoning, we would keep ApoB not too low…), so I don’t want to spend too much time on it. But I want to increase my low B12 (and check my B6…).

5 Likes
#71
#72

https://www.sciencedirect.com/science/article/pii/S0022316622110552#:~:text=Homocysteine%20thiolactone%2C%20an%20intramolecular%20thioester,incorporation%20of%20homocysteine%20into%20proteins.

#73

IMG_8101
IMG_81011179×886 172 KB

@adssx

https://wiley.scienceconnect.io/api/oauth/authorize?ui_locales=en&scope=affiliations+alm_identity_ids+login_method+merged_users+openid+settings&response_type=code&redirect_uri=https%3A%2F%2Fonlinelibrary.wiley.com%2Faction%2FoidcCallback%3FidpCode%3Dconnect&state=_YwKqZ4tCuZolOVbXMMQYAgxzRcaIyK7Ejb2Nll_Mxg&prompt=none&nonce=GKquhZCnqBQuiWMSI6MrsYR1vTcedRyg7%2B3IjVv9t4U%3D&client_id=wiley

2 Likes
#74

Thanks. More interesting that the association (that we already knew) is the potentially causal link:

Moreover, Index revealed a normalization of accelerated epigenetic aging in these individuals following treatment with tHcy-lowering B-vitamins. Our results indicate that elevated tHcy is a risk factor for accelerated epigenetic aging, and this can be ameliorated with B-vitamins.
We believe that high tHcy is causally associated with rapid aging because normalizing tHcy levels with B-vitamins decelerates biological aging over the 2-year duration of the trial. We suggest that accelerated aging may help drive the broad spectrum of maladies in people with hyperhomocysteinemia, including cardiovascular and neurodegenerative diseases, as well as cognitive decline (Smith & Refsum, 2021). These findings may have broad implications: an estimated 13.6% of men and 8.7% of women aged 60 years and above in the United States have tHcy level >13 μmol/L (Pfeiffer et al., 2008), putting them at risk for accelerated biological aging and severe health consequences. In countries that have not introduced folic acid fortification, these values are likely to be higher. tHcy can effectively be lowered with B-vitamins, which represents a safe and cost-effective approach to potentially reduce all-cause mortality risk, as well as many other adverse outcomes (Smith & Refsum, 2021) in the broader population.

(link)

I’m actually waiting for my Hcy results after 6 weeks of methyl-B12 2 mg/day… Should have the results today or on Monday…

6 Likes
Rapamycin, Serine + Vitamin B6: The Best Way To Reduce Homocysteine? (Homocysteine Activates mTORC1)
#75

My Hcy results:

  • April 2024: 18.1 µmol/L (baseline)
  • May 2024: 12.2 µmol/L (after 4 weeks of methylcobalamin 1,000 µg/day sublingual)
  • July 2024: 10.3 µmol/L (after 6 weeks of methylcobalamin 2,000 µg/day sublingual)

But at the same time, my B12:

  • April 2024: 302 ng/L (baseline)
  • May 2024: 426 ng/L (after 4 weeks of methylcobalamin 1,000 µg/day sublingual)
  • July 2024: 1,123 ng/L (after 6 weeks of methylcobalamin 2,000 µg/day sublingual)

My lab tells me that 1,123 ng/L is way too high and that the upper limit is 771 ng/L… So I guess I’ll go back to 1,000 µg/day supplementation…

4 Likes
#76

@adssx Perhaps you can add some of the B6 and B9 per eg Peter Attia’s protocol to belp keep Hcy down without going too high on B12.

My results after this protocol are below.

(The last data points also included taking creatine daily and not just on strength training days).

(I have not yet done, but think I saw that adding a bit of B2 can help also).

IMG_8119
IMG_81191179×1227 151 KB

IMG_8120
IMG_81201179×1207 148 KB

2 Likes
#77

Two interesting articles on homocysteine:

1 Like
#78

Yes, I think I’ll go back to methyl-B12 1,000 µg/day sublingual and add a simple B complex (such as this one) that includes B2, B6 and B9. Which B6 and B9 are you taking?

2 Likes
#79

Cyanocobalamin is as effective as hydroxocobalamin in lowering homocysteine levels in a randomized, crossover trial.

image

Comparative effects of hydroxocobalamin and cyanocobalamin – L_ John Hoffer; Orchidee Djahangirian; Paul E_ Bourgouin; – Metabolism, #10, 54, pages – 10_1016_j_metabol_2005_04_027 – 0e0baf169521ed6bae823fef1b9fbc86 .pdf (132.4 KB)

1 Like
#80

Well, do you have any data showing that cyanocobalamin harming kidneys without kidney failure?

The obvious risk is vitamin b12 deficiency from using a less studied and less shelf stable form of vitamin b12.

2 Likes
#81

Yes: “A trial in patients with diabetic nephropathy randomized to placebo vs. folate 2.5 mg, B6 25 mg and cyanocobalamin 1,000 μg daily showed faster decline of renal function, and a doubling of cardiovascular events, with B vitamins.” (B vitamins for NASH: Use methylcobalamin, not cyanocobalamin 2022)

Note: “Nephropathy is the deterioration of kidney function. The final stage of nephropathy is called kidney failure, end-stage renal disease, or ESRD.” We all have some kind of loss of kidney function after the age of 30/40.

image
image1324×1010 97.3 KB

image

Is the above relevant if your eGFR is still above 90? Not at all if you only occasionally supplement with low doses of cyanocobalamin. However, if you plan to supplement with B12 at a “large” dose (≥ 1,000 µg) for the rest of your life, then I think so. You might still prefer to use cyanocobalamin as long as your kidney function is perfect (eGFR > 90) and then switch to methylcobalamin if you ever go below that. To each their own way.

4 Likes
#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.

1 Like
#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.

1 Like
#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.

3 Likes
#88

image
image1124×656 50.6 KB

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

image
image1101×646 29.1 KB

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.