Homocysteine Update, What's Optimal For Vitamin B12?

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Papers referenced in the video:
Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands
pubmed.ncbi.nlm.nih.gov/31940...
Relationship between serum B12 concentrations and mortality: experience in NHANES
pubmed.ncbi.nlm.nih.gov/33032...

[@michaelransom5841]

I know this is old, but it is interesting to come back to after 2 years as the research has progressed further since the study in question. It seems the consensus now is that the rise in all cause mortality was a comorbidity driven association, as in those with diseases that increased the risk of death were more likely to take higher doses of b12 to help manage their conditions, which may have actually actually improved outcomes for many of these patients over the expected outcomes. This is an excellent example of the weakness of correlation studies. It is very difficult to pull out which is the cause and which is the effect, and that's if the two are actually directly connected.

[@viracocha2021]

Could you please provide studies? I've been trying to fix my MCV for 8 years without success, so this helps me a lot.

[@Golabekrafts]

I think it’s important to differentiate between supplemental b12 and dietary b12 as well..

[@Bshipbuilder]

Really appreciate your deep dive analysis and commitment to the process of discovery.

[@conqueragingordietrying1797]

Thanks Ben B!

[@iblisthemage]

This is very interresting. I am looking forward to see the results of your B12 blood tests when you get there. I will dive into B12 and see if I can get some level of mechanistic understanding of how it works, if there are tissue specific concentrations, etc. Thanks for your videos, they are fantastic :-)

[@conqueragingordietrying1797]

Thanks IblisTheMage!

[@sandy-qw4np]

Thank you ! Excellent explanation

[@conqueragingordietrying1797]

Thanks @sandy-qw4np!

[@MrGatward]

great stuff! I've been taking 2500 ug once a week.

[@stephenrose1902]

It would be interesting to compare intake vs. blood levels of B12 given that B12 absorption tends to decrease in tandem with changes in the stomach, pancreas, small intestine, it would difficult admittedly given the fact that the liver stores B12 for long periods of time.

[@conqueragingordietrying1797]

Yep, that's on the to-do measurement list, at least for diet vs blood levels.

[@monnoo8221]

Great, as always. You should sell your approach to an insurance company Yep, there is definitely an interaction. What about the correlation of the sum of normalised values? W hoch proteins are you feeding on, VDO you track methionine? The inverse relation is kind of surprising! As mentioned in the comment to the episode about serin and hcys, I strongly suggest to take a look at berberine. Hcys is likely not directly pathogenic, but through motor and IL signalling Thanks a a lot!

[@rhyothemisprinceps1617]

Review article - Nexo et al. 2011 - Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility

[@wahidrashidzada2446]

I do excercise almost every day and lift weights 5 days a week. My cardio excercise is mainly brisk walking anywhere from 5 to 9 miles a day with intermittent sprint running while walking. I weight range is 165 lbs 170 lbs. My BMI is 24. I eat grapes and 100% carrot juice every day. I also dont do any kind of fasting. I do take NMN and Resveratrol every day mixed in yogurt and 1 teaspoon of extra virgin Olive oil. I dont eat much red meat maybe every once in a while but do eat fish, chicken, red beans for my protein intake. I also take Niacin, B100 vitamins, Zinc, Magnesium, multivitamin, Vitamin D3 and K2. I do push ups and situps and other core excercises at home when Im not doing anything.

[@MichalS1984Y]

Amazing! This is the best, evidence and science based biohacking video blog on KZbin.

[@conqueragingordietrying1797]

Thanks MichalS1984Y. For some reason KZbin deletes external comments (but not mine!?) that have links in them, but I saw your other comment in my email. It's not coffee, as I rarely drink that (1x/month or less). It's not niacin or fiber, which I closely monitor and aren't strongly correlated with homocysteine. In contrast, higher levels of omega 6, and a higher 6:3 ratio are correlated with higher Hcy in my data. For my next blood test, I'll likely raise (I'm still exploring all the correlations) O3 and reduce O6 to see if this affects Hcy. It's possible I may not need B12 or higher protein to lower it, we'll see... btw, I have a more recent video for homocysteine! kzbin.info/www/bejne/g4CmgpRnmtWtosk

[@MichalS1984Y]

@@conqueragingordietrying1797 Thank you Mike! I have watched it already. It is excellent. Cheers! Michal Sporek

[@MichalS1984Y]

@@conqueragingordietrying1797 Another question I forgot to ask - is there any scientific evidence about microbiota link to ellevated homocysteine levels? I'm on a path to optimize my result and thinking about what options I might have. I have ordered a test for MTHFR mutation as this might have impact.

[@MichalS1984Y]

@@conqueragingordietrying1797 Continuing the conversation about homocysteine levels - I have made a genetic test myself to figure out today the MTHFR gene mutation (C667T). I guess I'm on a right path with this. Decided to go on a supplmentation of metylated forms of B group vitamins. Will see how it looks in 8-12 weeks from now. Expecting some improvement.

[@wahidrashidzada2446]

I eat grapes almost everyday and juice other fruits and vegetable as well. I juice Cucumbers with pears, apples, carrots and sometimes watermelon. I find that cucumber juice with or without other fruits is a great cleanser plus it keeps my blood pressure low which is great.

[@retire14pattaya9]

What is your blood sugar like?

[@felicisimomalinao1981]

According to research quoted by Dr. Stanfield, we must eat fruits whole, not the juice alone.

[@rationalsage1084]

B12 is also correlated with meat intake.

[@conqueragingordietrying1797]

Yes, true. But those effects are dwarfed by high-dose supplementation. For ex., my intake is > 10mcg/day without supplementation.

[@Battery-kf4vu]

I kinda doubt someone would reach very high levels of B12 from meat, he would have to eat mostly liver. Mmh might be wrong on that.

[@rationalsage1084]

@@Battery-kf4vu I'm sure eating meat can bring b12 up to 400.

[@conqueragingordietrying1797]

@@rationalsage1084 Have you measured it? Without supplementation I'm at ~10 mcg/d, but I haven't measured blood levels yet to know.

[@Battery-kf4vu]

@@rationalsage1084 400pg/ml? Sure, but that is not a problematic level. Point is, much more people take B12 supplements than eat liver every day.

[@rhyothemisprinceps1617]

High serum B12 is associated with lung cancer and colon cancer. B12 is an LRRK2 inhibitor, and LRRK2 inhibition promotes lung adenocarcinoma - so there is a plausible mechanism of action. OTOH most other cancers seem to go the opposite direction with higher LRRK2 activity increasing risk, including colon cancer. High B12 status was found associated with poor outcomes in Covid patients - alveolar type II pneumocytes, same as lung adenocarcinoma. Inability to control B12 release / store in liver due to liver dysfunction may be an issue in aging.

[@conqueragingordietrying1797]

Yes, great points. I'm thinking about a Part II for why higher blood levels of B12 are associated with an increased mortality risk, including some of that data.

[@henryp.]

No. Look at and control for all confounding factors and variables and b12 itself has no increased risk, in fact it's protective. kzbin.info/www/bejne/gZuninSvp51-bNk

[@randyalbertsw1992]

I’ve been using Thorne MethyGuard. The B12 component is 3 capsules twice daily. That’s 1.2 mg twice daily or 100,000 % of daily value. The last time I had my B12 tested was in 2016 and it was over 1,500. This was to help with idiopathic neuropathy and homocysteine which is 18 if not supplementing and 8-9 if supplementing. Will look for methyl Bs that have lower B12. Thanks for video.

[@jackbuaer3828]

1 Thorne capsule = 400mcg of methylcobalamin. Even just 400 mcg of methylcobaamin daily put me at 1.800 blood level. Though according to the supplement study in the video, people did ok up to 1000 mcg. Though we don't know what form of b12 they were taking in the study.

[@leighneal8989]

They did not exclude people with diseases requiring high dose b12 intake. So there was a selection bias towards diseases people on b12

[@wahidrashidzada2446]

I dont know how to explain it but my last homocystiene was 6.2 and I am 51 years old. My B12 was 473. I do take sublingual B12 anywhere from 2500mcg to 5000mcg but not consistently or necessarily every day.

[@ilmostromberg]

Hello Michael, really appreciate your work! As a quantified self-enthusiastic, I'm interested to know what tools you use to track your diet? Thank you

[@conqueragingordietrying1797]

Hi ilmo strömberg, and thanks! cronometer.com (not sponsored!), and then I enter the macro, micro, and total food amounts into an Excel sheet in conjunction with blood test data.

[@themidstream]

Make a change and something else comes up, mortality always 1 step ahead, what would you say is the most effective action/habit/supplement you have done to lower Homocysteine? Great pioneering content as always.

[@conqueragingordietrying1797]

Hey Al Sharif, as I mentioned in the video, B12 seems to have the biggest impact. Also, protein intake (see this video: kzbin.info/www/bejne/r2fNoHSmlLqanrM)

[@themidstream]

@@conqueragingordietrying1797 Thank you

[@lechsiz1642]

@@conqueragingordietrying1797 I am vegan, so this subject matters for me. Based on what I've read, B2 and intake of methionine matter, too. And, i just saw this on a 1-minute search: Conversion of homocysteine to SAMe requires adequate levels of folate, vitamin B12, vitamin B2, zinc, TMG (trimethylglycine from choline), and magnesium. What I gathered, was that, in my life, it seemed wiser to greatly lessen my methionine intake and/or to balance it well with lysine (I think it is nearly a 1:3 ratio...1: 2,8, to be more exact). For me, getting rid of most flour is how I do it (I am already vegan, so, of course no animal products). I am not a scientist, but got most of my info from scientific studies and i am a detail freak. I have not got my homocysteine levels checked, though. Another idea (one I'd like to implement myself) is to add choline by adding liquid lecithin to homemade sauces. When I worked at Joe's Crab Shack, i read the coleslaw sauce's ingredients and liquid lecithin was a main ingredient - it makes it thicker. It isn't that cheap. 30 years ago in NYC i paid $8 for a small bottle. But, it has almost no taste to it, so is an excellent idea for sauces and dips - especially for raw veg.

[@il3mendo]

Vitamin b12 deficiency are linked to dementia, schizophrenia, neurological disease, heart disease. High vitamin b12 ( just through diet) can be associated with folate/iron, vitamin b2 and vitamin b6 malabsortiin.

[@linofreek52]

Life is very complicated... i am still finding new things to take for good health and longevity but the trouble is ...the variables are great and it comes down to choosing what are the main things to concentrate on taking lol .

[@taymourheikal5031]

Would be interesting to see data on the correlation between blood levels of B12 and homocysteine. Perhaps one explanation for the data showing high B12 = higher risk of mortality is deficiencies in cofactors/enzymes that keep the remethylation and transmethylation pathways turning. If there are limiting factors in those pathways, maybe high B12 is implying a lack of methylation, and thus higher Hcy.

[@conqueragingordietrying1797]

All correlations for diet and nutrients with biomarkers are on the Correlations Tier on Patreon, but B12 is significantly correlated with lower homocysteine in my data (r=-0.58, p< 0.0001, 32 blood tests). That said, with 1000 mcg of methyl-B12/d, homocysteine is reduced only by ~10%, so other factors are involved (in my case). Yes on the methylation/remethylation pathways, and I've tried almost everything related-serine+B6, folate+b12+b6, TMG, increasing, choline, increasing non-traditional methyl donors (proline betaine, tryptophan betaine, trigonelline), but I'm working another hypothesis, with that video coming soon!

[@newdata]

the study on b12 and all cause mortality maybe is more related to meat comsumption to mortiality than b12

[@BobJ357]

Excellent summary as always! 👍. Any recommendations for good sources of B12?

[@CashMoneyMoore]

Beef liver has to be the best

[@conqueragingordietrying1797]

Thanks BobJ357, I use methylcobalamin from Jarrow (not sponsored).

[@erastvandoren]

Matjes. DHA/EPA/B12 with very little saturated fats and cholesterol and without Neu5Gc. 2 ounces a day.

[@BobJ357]

@@conqueragingordietrying1797 Thanks Michael! 👍

[@Battery-kf4vu]

@@erastvandoren Zinc and selenium also.

[@TheRagbags1]

I have Ehlers Danlos syndrome and pots and since extreme stress and hysterectomy I have very painful neuropathy, I think I’m MTHFR so I’m adding methyl folate As I had assumed it was mu b12 & clearly it wasn’t I have Macrocytosis.

[@TheShumoby]

You might look into MTHFR mutation

[@Pluvo2for1]

Hi, you mentioned something about a relationship between b12 and methionine. If you have some methionine data would a comparison between that and b12 be useful?

[@conqueragingordietrying1797]

It would definitely be useful, especially considering the link for methionine with lifespan. I could track methionine levels, but I haven't recorded that info in an Excel file for any of the past 6 years. Also, a limiting factor is that cronometer.com (not sponsored!) doesn't have amino acid levels for all of its foods, so if I did track methionine intake, it may be incomplete.

[@Battery-kf4vu]

Maybe you've stored a lot of B-12 in your liver during the time you were supplementing. So perhaps it will take time to see a significant effect on B12 blood levels and biomarkers after stopping supplementation.

[@conqueragingordietrying1797]

Maybe, and to account for that I'm going to keep an eye on biomarker-B12 correlations.

[@EstebanLarronde]

T-kiu!

[@CyrilAndPriscilla]

What could chronically HIGH B12 without supplementation mean--- like between 800 and 2000-- with homocysteine around 7.5 and no anemia?

[@FinTra_]

This is macro, and only specific to you personally and your lifestyle. For Hcy you should try nac, it is very effective in lowering Hcy. Nac is not only for Hcy but also CRP

[@conqueragingordietrying1797]

Yes, that's true, but we can all replicate the approach to identify what potentially impacts what, rather than blind hope based on RCTs. It all comes back to n=1 studies in the end.

[@ecrypto7006]

Could the higher mortality associated with B12 over 400 be because it decreases the effectiveness of folate So just up the folate to protect from negative effects of high b12

[@droliverzolman]

You need to include details of population and all confounder adjustments and other major flaws for each study and perform your own qualitative meta-analysis of observational studies along with showing search terms... otherwise its impossible to interpret graphs from your slides...

[@conqueragingordietrying1797]

Hey Oli, I pay attention to all that when making the videos, but if I do all that, I risk making these videos too technically heavy and boring...

[@Draziell]

There are some studies showing that serum B12 bellow 500 is already a deficiency of B12 at celular level and you should have something between 600-800 of serum B12 to have optimal levels... And the best way to know this is by mesuring Methylmalonic Acid

[@conqueragingordietrying1797]

How do you reconcile that with the data showing an increased all-cause mortality risk for blood B12 levels > 400 pg/mL?

[@herveduchemin2139]

In that meta analysis -- how many of those people were smokers, overweight, diabetic, etc?

[@drytropics]

You may need about 3g of betaine daily as well as the b vitamins. I have glitches in my CHDH gene, which is responsible for converting choline into betaine/trimethylglycine. I've been on high dose methylated/activated B vitamins and so far have got my homocysteine levels down to 13.5 umol/L, from an initial high of 48. To get it down that little bit more I probably need betaine, and that could assist in lowering yours. 6g is generally the recommended dose, but 3g is effective and has less chance of raising cholesterol.

[@garnerblair5179]

Folks need to look into magnesium taurate , quercetin, boron in regards to homocysteine

[@TheBwithers]

Foods highest in b12 are meat/dairy/eggs. These are all associated with increased all cause mortality. Maybe this chart shows association not causation?

[@conqueragingordietrying1797]

There's more to the story than that in the video...

[@TheBwithers]

@@conqueragingordietrying1797 Dietary b12 increases morality while supplements do not. That indicates it is not the b12 itself but something else that is common in foods high in b12.

[@conqueragingordietrying1797]

@@TheBwithers I wish it were that simple-very high B12 levels are found in critically ill patients, and I doubt that's diet related: pubmed.ncbi.nlm.nih.gov/28025528/

[@jackbuaer3828]

@@conqueragingordietrying1797 It might be somewhat simple if there are three independent reasons for the varied results amongst dietary intake, supplements, and disease status 1. High dietary intake may be a surrogate for high animal protein which may increase mortality. It's a reasonable theory. 2. Supplemental B12 up to 1000 mcg may not detrimentally affect health, at least according to the one study you cited. This may be because B12 in this case is not inflated due to disease or high animal product intake (It would be nice if there were additional studies to confirm that supplmental B12 up to 1000 mcg does not negatively affect health). 3. High B12 may be an indicator of bad health in critically ill patients because their livers or other bodily functions are failing. "Some studies have indicated that elevated serum levels of vitamin B12 might be a sign of a serious and life-threatening disease. Such falsely high valued of serum vitamin B12 levels are observed in myeloproliferative disease, acute hepatitis, severe alcoholic liver disease, and cirrhosis." It might be reasonable to presume liver disease might cause B12 problems since several years worth of B12 are stored in the liver per the Merk manual. I don't know what the myeloproliferative connection might be. pubmed.ncbi.nlm.nih.gov/21899932/ www.merckmanuals.com/home/disorders-of-nutrition/vitamins/vitamin-b12-deficiency#:~:text=(See%20also%20Overview%20of%20Vitamins,to%205%20years%20to%20exhaust. Anyway, those are some possible theories

[@conqueragingordietrying1797]

@@jackbuaer3828 Yes, great points. #3 may go into a future B12 video, and imo is the under-reported part of the B12 story.

[@jimroth7927]

If you eat a lot of meat your all-cause mortality risk goes up. Eating meat also raises B12 levels. The meat is probably the culprit, not the B12.

[@nerin3624]

What about absorption… it’s a key..

[@lost0071000]

I wonder if people with more B12 had other problems, as B12 often comes with food high in saturated fats.

[@conqueragingordietrying1797]

Yes, definitely possible

[@Ivana.0405]

B12 correlates with all-cause mortality, but causation is unclear, isn't it? Could high animal protein intake drive B12 and also mortality? Said differently, high B12 that is the result of supplementation, not of high consumption of animal protein, may not be associated with higher mortality. Could this reasoning have some merit?

[@conqueragingordietrying1797]

Definitely David!

[@tommyortiz6623]

I hope you see this message I watch all your videos I’m a big fan! I have 8 deficiencies from spectracell test I did. What can cause this 8 deficiency in selenium, b12, Pantothenate, chromium, B6, inositol, zinc, folate? I am taking menthyl b12 shots IM weekly and oral supplements daily. I really need your help as I have digestion issues plus nerve sharp needle pains throughout body. I have been eating clean and lost weight now in normal weight range with intermediate fasting and eating fish and salads for this last year. I’m not sure if it’s from vaccination or not but it started 1 week after first shot. Pls help🙏

[@lost0071000]

I would check your microbiota. And talk with a doctor.

[@tommyortiz6623]

@@lost0071000 how? Which microbiota kit?

[@lost0071000]

@@tommyortiz6623 I don't know any kit. I would try magnesium and probiotics. And check with a doctor who may suggest a colonoscopy.

[@wizardatmath]

Which b6, b12, and folate were u taking?

[@conqueragingordietrying1797]

Jarrow, this exact product: www.iherb.com/pr/jarrow-formulas-methyl-b-12-methyl-folate-lemon-100-chewable-tablets/69333?gclid=Cj0KCQjwsdiTBhD5ARIsAIpW8CL4E8d4sp4Fm-2vAjQntWaLOS096WCNLsKXWPbqaFg6Be8I3ChjTZ8aAllDEALw_wcB

[@zulkiflicurran94]

Do you think elevated homocysteine give a raise in cholesterol & HDL levels?

[@conqueragingordietrying1797]

I can directly look at the correlation for homocysteine with HDL and total cholesterol in my data (13 blood tests since 2017): weak nonsignificant correlation with HDL (r = 0.19), but higher homocysteine is significantly correlated with lower total cholesterol (r=0.57).

[@FinTra_]

B12 alone,in high cincentrations, is an independent cause for all cause mortality.

[@conqueragingordietrying1797]

I recently took B12 supplementation out of my approach (kzbin.info/www/bejne/noHQqWV3hLSHbbc), we'll see how the data looks on the next blood test.

[@larsnystrom6698]

I don't think the figure with serum B12 level and Mortality tells the full true story It seems that increasing B12 with supplementation doesn't increase mortality. What's happening is that several diseases increases the level of B12 in the blood! Cancer and liver disease among them. This totally corrupts the interpretation of high B12 in the serum being dangerous. I couldn't find research about supplementation of B12 and mortality, though.

[@garnerblair5179]

High serum b12 may indicate poor utilization . Switch to low dose methylcobalamin

[@conqueragingordietrying1797]

Lower doses didn't make a dent on homocysteine... No worries, I'm working on a video that will focus on methyl donors, and not just TMG

[@garnerblair5179]

@@conqueragingordietrying1797 only meant as a starting point .

[@surfreadjumpsleep]

I was also taking 1000 ug/day. So you solved this by taking 1000 every other day?

[@conqueragingordietrying1797]

I wouldn't say solved it, as my current homocysteine is still above my 2005 - 2009 average. B12 is correlated with a 20% reduction, which is going in the right direction, but there's more reducing to be done, and I'm looking into how to do that in my data.

[@surfreadjumpsleep]

@@conqueragingordietrying1797 I am very interested to hear the results of that research. As for now, your approach is to take 1000ug every other day? I'm asking because I have the same problem I have these pills which are 1000ug and cannot be split, so I'd also like to cut my B12. Just take it every other day? (edit 11/21. Duh I just realized my pills are 500mcg. I'm taking vitacost B12 500mcg.

[@conqueragingordietrying1797]

@@surfreadjumpsleep Yes, I'm taking it every other day, for now. I may experiment with every 3rd day, but I haven't made that decision yet.

[@ramim.j2091]

A higher intake of dietary B12 is associated with all-cause mortality because the main source of B12 in diets is animal proteins. And there have been numerous studies indicating the negative impact of animal protein on mortality and age-related diseases. It also explains why B12 supplements don't increase mortality but dietary intake does, Because the latter is simply a surrogate measure of meat and dairy intake. Nothing surprising about these results.

[@conqueragingordietrying1797]

Without supplementation, my B12 intake is < 10 mcg/d, which would put me ~400 pg/mL, which is not associated with an increased all-cause mortality risk. I didn't include it in this video, but very high B12 blood levels may be reflective of poor health: pubmed.ncbi.nlm.nih.gov/21899932/

[@abritrn]

The study referenced at 7:32 with the graph is an association study that excluded people who supplemented with B12, meaning they had to get those elevated blood levels via diet alone (or they somehow lacked the ability to use the B12 they had therefore it was building up) which supports the idea that maybe these subjects had high animal food diets /low plant food intake. Maybe the high blood levels of B12 are just a proxy for something else.

[@hugueshenrion6642]

@@abritrn Thank you for this very useful piece of information

[@aquie4d999]

Probably the high B12 correlation might come from chronic high exposure to animal products in the diet, over long years

[@monnoo8221]

and what if B12 is upregulated as aconsequence of elevated homocystein, the latter being the actual culprit? You are committing the same fault in reasning as the anti-cholesterol fraction 40 y ago...

[@conqueragingordietrying1797]

Homocysteine activates mTOR, so it's likely to be bad for longevity... pubmed.ncbi.nlm.nih.gov/28148781/

[@monnoo8221]

@@conqueragingordietrying1797 Yeah, that was my argument, or... Not quite. I'd B12 is setting Homocysteine, and Homocysteine is bad for health, then a balanced physiological state should upregulate B12 absorption.. in that case any reasoning about an association of B12 with mortality is going into the wrong direction

[@monnoo8221]

Body does not make B12, and in this range he is likely be super saturated with it, hence no influence of any would be regulation

[@juliahello6673]

B12 is a marker for meat, which is probably why it increases all-cause mortality

[@galaxymetta5974]

Supplementing with 500 mcg a day is intuitively unnatural as it significantly exceed the dietary intake of even the most heavy meat eaters. Not my cup of tea. Cheers.

[@conqueragingordietrying1797]

You can make that argument about every supplement or drug. Is it net beneficial for systemic health, neutral, or detrimental? For me, at least for now, it seems to be beneficial, as it's not only correlated with lower homocysteine in my data, but 3 other biomarkers in the right direction, with 2 going in the wrong direction, out of 20 comparisons.

[@0235282094]

Levels of B12 say nothing once people start supplementing, it is in no way accurate anymore, especially not serum level. Even when measuring ACTIVE b12 in the blood ( a more expensive test) one needs to stop supplementing AT LEAST 3 weeks to measure otherwise it's useless. Furthermore, the study shown shows a correlation. It could very well be that the people involved in this were taking B12 supplements because they were already sick before, hence the correlation. It makes no sense that B12 levels (especially after supplementing) would be causative of any disease as any excess is peed out. Other than that, I have enjoyed your video in regards of your self study in lowering your homocysteine.