Homocysteine Increases During Aging, But Can Be Reduced With Diet And Targeted Supplementation
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- Опубликовано: 30 июн 2024
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Papers referenced in the video:
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway:
pubmed.ncbi.nlm.nih.gov/32130...
Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels:
pubmed.ncbi.nlm.nih.gov/27567...
Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study:
pubmed.ncbi.nlm.nih.gov/7474221/
Total plasma homocysteine values among elderly subjects: findings from the Maracaibo Aging Study:
pubmed.ncbi.nlm.nih.gov/16959...
Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies:
www.ncbi.nlm.nih.gov/pmc/arti...
Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies:
pubmed.ncbi.nlm.nih.gov/30826...
Association between Homocysteine Levels and All-cause Mortality: A Dose-Response Meta-Analysis of Prospective Studies:
www.nature.com/articles/s4159... 
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Some animal protein sources contain creatine, which in turn reduces homocysteine (in some studies). That might be an explanation as to why some specific types of protein increases may reduce homocysteine.
I've got Hyperhomocysteinemia Accelerated Atherosclerosis and have only recently come across the many benefits of creatine. As creatine production uses up a huge chunk of the available methyl donor groups I theorised it could help bring my homocysteine down by leaving more methyl donor groups available for converting homocysteine back to methionine. The other main user of methyl donor groups is phosphatidylcholine so I'm looking into supplementing with that too.
@@drytropics How much more creatine than the average recommended daily amount on a supplement package, do you suggest? Would it be by body weight, age and gender? Thank you :-)
@@creativesolutions902 heart will be safe and ur kidney will be gone
@@creativesolutions902 The MDs on youtube recommend 5 grams daily.
@@BlackMamba-lt8oe there is no evidence in hundreds of studies tat creatine affects the kidneys
A different thought on what may have lowered homocysteine. A delayed response to B12 supplementation. - I had a similar response. Ihad both high homocysteine and MMA. After beginning B12 injections and oral folate, MMA decreased before homocysteine did. It took a few months and then dropped. With later changes in B12 dose, change in homocysteine also appears slower. - So, maybe related to either how the body excretes homocysteine and/or how long or how much B12 (cumulative) that you need to change B12 storage and utilization. ~ In my experience, it takes maybe 2-4 months to change your labs. Interestyly, it appears to me that it also takes longer for homocysteine to increase compared to MMA.
Use NAC and b complex. Both proven to lower homocysteine, nac lowers significantly hyc in combo with glycine even better.
Thanks for this beautiful analysis. I'm 67, my Homocysteine is at 7.0 umo/L, high % protein diet, methylcobalamin 5000mcg/day sublingual, Intermittent fasting (~18 hours).
I pursued this because I have a genetic flaw (MTHFR) which is associated with poor Folate and B12 metabolism. See why I enjoyed your presentation?
Very high vitamin b12 intake can cause lung cancer.
@@quandmeme9970 what does very high means ?
If your HOMOCYSTEINE is high, there is a high risk of heart attack or stroke
This was an excellent analysis, thank you.
This is one of the best medical information dats sites on the internet!
Thanks Bob!
Brilliant video. The topic could easily be explored over a number of videos.
Thanks IblisTheMage! I may do that, especially since Biff (commenting above), shared this paper showing no effect of NR supplementation on homocysteine levels:
www.nature.com/articles/s41598-019-46120-z
@@conqueragingordietrying1797 Doctor I have homocysteine at 50 and I take 5 mg of folic acid. I have the mutated mthfr c677 tt gene. What other things should I take in what dosages? and are there any gene therapies to fix permanently?
@@deepshadow1 I can't say what's optimal for you, but I can promote the approach-blood test many times, and try different interventions-that will help you figure out which works.
@@conqueragingordietrying1797 thanks so what values should i keep under control? and which supplements to try? and what would be a specialist to turn to? also i think the fact that it is inflammatory for the body led me to high estradiol levels even though i have high dht and normal testerone
Very informative video. Many thanks.
Fascinating and so well explained. Thank you
Brilliant video
Thanks. Important information.
an excellent analysis!! as an aging 78 old man, MTHFR mutation, predesposing me for high systein. I have tried a lot, but the idea with protein intake was new to me.
I can't say if higher protein will work for others, but that's what my current correlations still show...
Great stuff. All these videos are so fun, relevant and spot on. Thank you! An Alzheimers scientist just told me that my b12 supplementation for homocysteine doesn't effect the risk for Alzheimers but will lower homocysteine levels. Curious about your thoughts, since I don't have your formal education. But, yet my Bredesen Re-code report says to prioritize b12 which contradicts with what he said. Thanks. I have always been a fan of DMG for NAD supplementation and mentioned it in the first podcast on NAD with Ben Greenfield. And there is some sucking up of Krebs cycle metabolites, I think. But, It appears we can now look to methylfolate as well. But, we all have very different pathways. My MTHFR pathway is heterozygously limited at the two SNPs. That Alzheimers scientist recommended supplementing with creatine. I wonder if creatine confounded your analysis being that so many people that count macros lift weights and take creatine. And Maybe that will help too besides simply getting more out of my weightlifting workouts.
Hello, if Alzheimers is a particular issue, suggest looking at the latest MedCram video re sauna benefits with Dr Rhonda Patrick. Apols if you're already following. ruclips.net/video/RWkv9ad7zvc/видео.html
found a paper titled: "Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state" the advocate for rather small does of things to correct MTHFR issues.
Wow. Thank you. I’ve struggled to understand the relevance of B12 to Alzheimer’s. But now I see it. It’s all about how it enables the body to make glutathione. Great video on so many levels.
What is good
VERY interesting!
Very interesting.
Based upon the chart at 28 seconds in, it would seem that NA might be better a strategy than NAM for boosting NAD if a primary factor in one's NAD+ boosting strategy is to keep homocysteine as low as possible
that's not the only benefit of na over nam, nam inhibits the enzymes nad boosts before being converted into nad, from what I've heard.
Thanks for great info
Always great vids Så THANKS :)
and ... Please keep on the good work !
, have you considered the effects of rebounding on aging markers?
Appreciate your contribution to the layman.
Thanks Zel Men. By rebounding, you mean jumping on a trampoline? Finding exercises that you like is important, and if that's what works for you, go for it! The question is, how often, for how long to gain exercise-related benefits. I incorporate jumping into most of my workouts for up to 3-minutes of consecutive jumping time.
Thanks Michael.
Very useful info.
Homocysteine goes up w Niacinamide supplementation
Homo accumulates when VitB6 is low, and Glutathione(GSH) drops as well
Same for Vit B12
higher protein intake, the lower homocysteine levels
Great work, as usual.
My thought was to possibly improve the b12 measurements from intake to actual testing of blood level b12. A bit more costly, but other than cost would there be any reason to think this wouldn’t be the better b12 measurement to correlate with? (Am thinking that for whatever bioavailability or product fault, the b12 intake might not actually be a good measurement of actual b12).
Thanks Swen. To see if it is indeed B12 driving this, I've removed folate and B6 from my supplements. As you mentioned, quantifying blood levels of B12 would be a potential next step.
@@conqueragingordietrying1797 Chris Masterjohn states that even just adding B2 can reduce the homocysteine levels 40%. Why protein might help? Perhaps it's has something to do with creatine or glycine.
I do supplement with Niacin. I also have been supplementing with Betaine to counter. I am a vegan so the only protein I take is through plants. I also have to supplement B12 being a vegan. But I think I’ll up it from 500 to a 1000 daily now. Thanks for sharing.
Meat eaters only get B12 because they supplement the conventional livestock with B12 as they never see a blade of grass in their lives.
Eat self grown organic produce, especially berries and you'll have B12 apparently and don't wash the berries.
@@shantinaturechild3239 You do realize that meat eaters also eat vegetables, right? Humans are omnivores. We meat eaters get B12. Some of us also eat grass fed beef.
@@theeclectic2919 Shanti gets her B12 from dirt, apparently...
@@shantinaturechild3239 It's not a reliable source. You may put yourself at risk of certain pathogens, better to just buy a cheap cyanocobalamin supplement and use that.
I’m 69 and went on a low animal protein diet to counter Prostate cancer progression. It worked but my creatinine levels doubled putting me into stage 3 kidney failure. I lowered methionine intake 70% but did not supplement B12 consistently.
And what was the result of your adjustment, please?
@@johnolaoluwa he is dead
As to why elevated protein reduced homocysteine levels, it may be relevant that serine is a necessary substrate for the conversion of homocysteine to L-cystathionine by the enzyme cystathionine β-synthase (CBS). Hence either serine depletion or CBS inhibition would result in homocysteine buildup. CBS also augments prolyl hydroxylase (PHD) activity, such that CBS inhibition inhibits PHD activity. Amino acid influx and homocysteine both activate mTORC1, but mTORC1 activitation by amino acids is also dependent on PHD activity. . Durán et al found that amino-acid starvation leads to PHD inactivation, and PHD inactivation prevented mTORC1 activation by amino acids.
@Amara Braun Thanks very much, Amara. It happens that I take potassium citrate and also milk thistle, for reasons unrelated to homocysteine. I was not aware that they might also lower homocysteine levels. I love to learn.
Certainly enjoyed a lot Sooo interesting , I knew the relation between Homocysteine & B12 , however did not know that proteins might have an effect too Thanks soo much Dr Micheal What I find very strange that once I start taking methylated B12 it shoots up within 6 weeks Then I have to stop again What could be the reason ?
It could be genetic and/or dietary precursor deficiency (B12, folate, B6, others) as examples. Discovering what impacts what is the major theme of my YT channel!
Hi Michael. You switched to a lower B12 dose, if I remember correctly. Did you circle back to see if there was an effect on homocysteine? Thanks!
Hi Matthew, I’ve taken it out for a few tests. I covered recent data for homocysteine in this video:
m.ruclips.net/video/PZhKr-9wRws/видео.html
My second time watching this yt. I have been focused on homocysteine for a while .. for. 20yrs mine has been stable at 10.3, I’m increasing b12:from 125mcg to 300mcg with a goal of homocysteine around 9 … no idea why I’ve chosen 9 (as a target for homocysteine) … thank you for this excellent series.
What is 9
@@BlackMamba-lt8oe as a target for homocysteine … sorry I should have been clearer.
@@jp7357my homocysteine is 24 and my age is 22 , what to do .
the inverse relationship of protein intake with homocysteine is intriguing... since more protein also means more methionine, which - ceteris paribus - would lead to an accumulation of Hcys.
I think there is a tight relation between B12, NAD and protein, and your style of hacking moved the whole metabolom to a different profile \ configuration.
I think, to conclude in favor for single cause vs co-factors one = would have to combine relatively lower protein of about 100..110g with high B12.
Cronometer also splits the protein into the involved amino acids... did you check them for the relation to Hcys?
What kind of protein were you consuming? It could be the choline, especially if you were eating a lot of eggs or organ meat. "One of the functions of choline is to serve as a precursor of a compound known as betaine or trimethylglycine. Betaine aids in the remethylation of homocysteine to methionine via the enzyme betaine-homocysteine methyltransferase (BHMT), thus serving to lower homocysteine levels in the blood."
Mostly plant-based, but sardines (90-100g) and yogurt (150g) every day. In my case, betaine did not affect homocysteine.
@@conqueragingordietrying1797 oh yeah good point
@@conqueragingordietrying1797 have you thought of getting your mercury levels tested? Not that Joe Rogan is someone to emulate 🤣, but I heard that he ate fish and got his mercury levels tested and was surprised by how high they were.
@@MaxwellPietsch Hi Max, definitely. While we wait for that, wouldn't we expect to see worse biomarkers with a higher fish intake? Or, more blood biomarkers going in the wrong direction than right in correlation with sardine intake?
@@conqueragingordietrying1797 I think so :) I suppose the additional mercury measurement would increase your confidence level overall, but you can have pretty high confidence levels already.
Side note - I eat canned alaskan salmon every day and find it delicious. I wonder if youd like it. It’s supposedly lower mercury but I havent done any blood tests yet.
One thing I would do different: check nutrient intake 2-4 weeks (check trend and average) before HCY test, not just on the day or the day before. Also check B2, Zn, Mg (some one-carbon metabolism enzymes are dependent on them) and Choline (although if Betaine supplementation didn't work, probably Choline won't make any difference).
For each blood test measurement, I take the average dietary intake that corresponds to it. For ex., if I test on Jan 1 and again on March 1, the average dietary intake from Jan 2 to Feb 28 is the intake that corresponds to the March 1 measurement.
@@conqueragingordietrying1797 Got it, that's a good approach, I should have expected no less :)
A quick scan of the literature indicates that the type of dietary protein is controlling. Egg white will convert homocysteine back into methionine, for example.
Also,
www.ncbi.nlm.nih.gov/pmc/articles/PMC4176105/
Danke!
Danke für deine Unterstützung @bogitruth!
Could you be increasing Adenosylcobalamin and thus upregulating L-methyl-malony-CoA mutase,so as the dietary protein increases the enzyme fuction increses cellular energy in the mitochondria where Adenosylcobalamin is used?
Goog question, Bob. I'm going to need to think about this a bit...
It's amazing how many knowledgeable doctors and advocates still use the term "Folic Acid" interchangeably as Folate and/or Methyl-folate. Folic Acid is synthetic and NOT the same as Folate or Methyl-folate.
Preach! This makes me CRAZY, especially since Folic Acid completely shuts down my liver, while meat sources of FOLATE make it happy. We need to teach people that Folic Acid is in most processed foods and may have negative health consequences, especially for those of us with bad Detox profiles (SNPs).
www.drbenlynch.com/folic-acid-side-effects/
@@anitamartini5144 Through a process called De Novo Biosynthesis, the body can take Tryptophan and create NAD but that doesn't mean we should call Tryptophan vitamin B3.
@@anitamartini5144 Did you read the link in my thread?
@@ybigirl Yes. I'm well educated on this subject and found no useful information that I didn't already know. How would this article have been worded if written before Folic Acid was given it's name in 1945. Folic Acid is synthetic and not found in food. Folate is the term used to encompass all forms of the vitamin found in food or the synthetic form Folic Acid.
@@rdance3 I was replying to Anita ;)
She doesn't seem to understand how toxic Folic Acid can be due to being synthetic.
So does NAD+ supplementation also increase homocysteine? Are the correlations with various diseases present after adjusting for age?
Yes
Thanks
Question about protein lowering Homocystein levels: Possibly with the higher protein intake there was going on also some Betaine intake. It is mainly the Betaine which causes homocysteine to be lowered. B12 makes only minor contributions to lowering Homocysteine. (Small effect compared to the very high dosage of B12 taken here)
As I mentioned in the video, 4g of betaine/d didn't impact my homocysteine, so I think it's unlikely that the correlation for higher protein with lower homocysteine is related to betaine.
@@conqueragingordietrying1797 would need to see protein but if it is collagen or bone broth, those are high in glycine and glycine helps clear methionine from body, I think. So it mimics methionine restriction, which has some of the same benefits as Calorie restriction.
@@diamond_s It's not collagen or bone broth...
Thanks. Another variable to consider. Bio availability of proteins animal vs plants. Given i eat all my proteins from meat (150 gr/day and weighs 75kg) given my high level of exercise which is >10 hrs of road/ mountain biking, weight and fast walking, i dont think i need supplementation to balance my vit b12.
Hey ccamire, while that makes sense, beyond the subjective feel, blood testing would provide objective data to see if it's true (or not)...
If you increased your protein intake, then you either increased your caloric intake, or you decreased the other macros. Could the impact on homocysteine could be causally related to those other changes? For example, did you replace some of your carbs with the increased protein? Fans of low carb diets claim many health benefits from decreasing carb intake.
I think that protein and B12 are strongly correlated, so we can't get a definite answer.
Possible one or more amino acid profiles help in some type of elimination process. ??
Hello sir are you suggesting to avoid taking a b complex containing niacinamide ?
It's interesting that you previously had high homocysteine and also Lp(a) and were able to bring both down through dietary interventions. I have a genetic disposition towards poor MTHFR and high LPA. I wonder if it's a part of the same underlying mechanism. In my phenotype I wonder if poor methylation --> lipid oxidization --> Lp(A) upregulated in response
It's possible, and from my experience, both homocysteine and Lp(a) are malleable, regardless of what the published studies in other people show. The trick is discovering what impacts them for you.
Lp(a) is a direct response to injuries of arteries. It goes in parallel with homocysteine because Hcu«ys is precisely doing that: injuring arteries
I watched a British doctor explain how the studies are showing the B complex + omega 3 fatty acids for some reason not yet understood may be the key to keeping homocysteine in check, as neither on their own did great, so if you were eating salmon or grass/pasture raised meat, that could potentially explain why you noticed a higher reduction once protein was increased. Maybe your omega 3 (inflammation lowering) increased and worked with the B12 synergistically.
O3 is relatively high (9g/d), but homocysteine remains ~10-11, so I'm doubtful about the O3 connection. O3 is also not significantly correlated with CRP in my data, so they're not inflammation-lowering for everyone.
The protein probably helps most by nourishing the liver's high demand for protein.
Typically, more red meat equals more methionine and more homocysteine. But HS is a measure of B vitamin status. And yes, creatine does allow for recycling of HS to methionine. So, its the recycling part that is improving here. And also HS is adjusted by the SAH I believe in regard to GSH. So, if you are more inflamed it will use HS to make more glutathione
animal protean contain more methonine an element in the homocysteine chart cycle , so wonder if it make a difference if protean is animal or plant based plus animal protean associated w negative outcomes in other aspects
I'd bet that it does-most of my protein intake comes from plants, although I do have regular animal protein in my diet, too (daily sardines, yogurt).
Starting to see the pattern. Ironically when I consume 6 lightly scrambled eggs I noticed a significant mental boost. It’s the combination of high protein plus high choline that was lowering my homocysteine levels. Plus eggs are high in other nutrients.
That could be true in my data, I've increased choline intake for the next test, but also B12, so we won't know which lowered homocysteine...
@@conqueragingordietrying1797 if it’s no trouble can you look into if Creatine lowers homocysteine levels? Michael Gregor on Nutrition Facts has a few videos that highlight creatine lowering homocysteine levels. Worth taking a look.
Don't some B vitamins interfere with blood labwork? If I experiment with B12 and remeasure homocysteine can I take it the day before (or morning of) that labwork?
Didn’t you find a correlation between higher B12 levels in serum and all-cause mortality?
That data exists, and is the main reason I'm experimenting with lower doses to try to keep my homocysteine low, but also reduce any excess B12-related risk.
great! what was your level of albumins, creatinine, b6, b9 and b12 through this experiment? did you take liposomal, tablets or any other form of b12?
There are albumin and creatinine videos on this channel, as is diet data...Methyl-B12, sublingual.
@@conqueragingordietrying1797 oh, i found it. thanks for your valuable opera! i wonder did you take animal or plant based proteins? results are in trials - oposite. i showed your site to my naturopath and she is astonished! she said that i have to cure my disbiosis/microbiota first. my b12 (measured) is 417pmol/l (138-652 is a ref) and folate 22,1 nmol/l (7-46,4 is a ref) are low, and they should be close to upper level. to believe or not? also she said that normal value of hc is (ideal) 7,3 and my is 12,1. high, but not to high. i'm 54.y.o.
@@domagojbarac Yes, I include animal and plant proteins in my diet-a full breakdown is here:
ruclips.net/video/PZhKr-9wRws/видео.html
Great video as usual! Thanks for sharing. I do have two thoughts for you about your protein intake and lower homocysteine!
1) in addition to the b vitamins and TMG you mentioned, glycine and serine are both required in the methionine cycle to prevent homocysteine build up. Increasing intake of these may be playing a role.
2) The fact that you mentioned that protein may be coming from eating peas, you may be increasing spermidine intake which may be the limiting cofactor in SAM metabolism and may act to divert methionine away from homocysteine production.
I agree with another commenter that this subject may be good to explore further in a follow up video.
Possibly the increased serine intake associated with the extra protein intake?? Thus reducing the homocysteine level...
My guess would be that protein is helping your home assisting because animal meats and I believe even dairy are high in methionine.
Regarding how elevated homocysteine with age can lead to dementia..
perhaps your increase in B12 / protein had the highest effect in lowering homocysteine levels because the other nutrients in your body where at sufficient levels? Maybe to play it safe, it's best to supplement with all (B6, B12, B9 / Folate , Betaine / trimethylglycine , Protein)?
I removed B12 from the approach
(ruclips.net/video/hPmx2AOOT7U/видео.html),
so we'll see the impact on homocysteine on the next blood test.
Maybe you should try 6g of betaine instead of 4g, as studies show lower doses of betaine do not effect plasma homocysteine levels? The normal dose of betaine for hyperhomocysteinemia sufferers like myself is 6g, preferably taken as three 2g doses throughout the day.
instead simply looking into why protein decreases homocysteine, it would be interesting how the individual amino acids r connected to that
im sure thats where the solutions lays - some amino acids will probably worsen it and many will improve it - and then smartly supplementing with those that lower it (if u want to decrease homocysteine) might be the way to go (so u dont have to go to ridiculous amounts of total protein intake and mess up other numbers in the process of doing so like igf-1/mtor)
Have you tested your NAD levels? Your B vitamin levels? Your fatty acid profile?
I haven't, but my biological age is relatively youthful:
ruclips.net/video/G5zXa4DLvjY/видео.html
Curios, if you reduce your protein intake based on your correlation then homocysteine should go up?
If correlation = causation, then yes. Note than a few nutrients are significantly correlated with homocysteine in my data, so if I kept them the same and the only change was protein intake, that would suggest causation.
Since I made that video, protein intake still has the strongest correlation with homocysteine (r=-0.77, p< 0.0001, 20 blood tests).
U need to do a reaoted measures analysis. Ur static are naive. Perhaps also a multivariate generalized linear model
What about methionine in protein ? It could be that’s actually methionine and not glycine which lowers Homocysteine..... that’s explains why TMG didn’t work lowering your Homocysteine
Most trials designed to lower homocysteine by supplementing with b complex vitamins have been unsuccessful in demonstrating a significant outcome. For example:
Conclusions In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up.
In a recent prospective trial published in jama. The theoretical advantage of B12 and b complex vitamins to lower homocysteine and protect patients from complications so far has been unfruitful.
Has this theory been tested in countries on people without our folic acid sprayed crops?
Aminos from protein sources are not linear, so homocysteine might be used up more in some during utilization? Also, I have a hard time believing DMG, B-9, and B-6 won't bring the H-Factor down--like B-12. Perhaps, you are overlooking certain mineral combinations in your thinking in the lowering effects during conversion? SAMe will also lower the H-Factor. James Braly already published this in his 2003 book.
TMG didn't work for lowering my homocysteine, that data is in the video. Just because something works in a given study doesn't mean it works for everyone. I also showed data that folate and B6 intake were not significantly correlated with lower plasma homocysteine, but a higher B12 intake was significantly correlated with lower homocysteine. To test that more directly, I stopped supplementing with folate and B6 for my next blood test, and only supplemented with B12.
What is the amino acid profile of your protein. Proline/Glycine levels.
While cronometer tracks amino acids, it's tough to say because all of its foods don't have that data. For ex., during the past 4 weeks since my last blood test, my glycine intake is 2.7g/d, and proline isn't listed in their data.
@@conqueragingordietrying1797 The reason I mention it is that a lot of people claim that high protein diets lead to shorter lifespan, but there are studies that seem to contradict this.
High protein diet in fruit flies leads to them having many more babies, but shorter lifespan. They accepted this as gospel.
Then someone decided to give fruit flies good cholesterol along side high protein diet. The fruit fly went on to have lots more babies with no lifespan restriction.
Humans are more complicated than fruit flies and create our own good cholesterol if we have a decent diet. That isn't the protein metabolism rate limiting factor. Amino acid balance appears to be.
We know proteins with high Methionine lower lifespan, but studies show us having high Glycine in the diet counteracts the negative effects of Methionine. In fact there is a study of mega doses of Glycine in the diet of the elderly in Japan that seemed to indicate it reverses aging in many cells.
Then you have the branch chain amino acids. Too many of them can lead to lifespan decreases through messing up of protein unfolding which, at least some anecdotal studies seem to indicate, can be normalized by Proline.
Body builders using BCAAs not only experience life span decreases, but have improperly formed muscles, more prone to injury, possibly cancers, mostly due to aberrant protein unfolding.
Proline plays a role in protein unfolding.
There hasn't be enough research into the appropriate amino acid balance in human diet.
I have a feeling a high fat, high protein diet, with appropriate amino acid balance, might end up being king for anti aging, anti obesity, fertility, and overall health.
@@darkhorseman8263 Beyond dietary recommendations, I always support blood testing to see what works, and what doesn't. Otherwise, it's just guessing, even if it's educated.
@@conqueragingordietrying1797 Glycine reverses aging in connective tissue www.nature.com/articles/srep10434
@@conqueragingordietrying1797 RUclips has a habit of blocking links I try to post, for some reason.
Hi Michael, you mind me asking your weight? My homocysteine levels came back at 13.7 so I would like to try the B12 and protein strategy.
Hey Think Supersystemic, my weight is an average of 157 lbs for the past month (I weigh myself daily), 5'7. I can't guarantee that my approach will work for you, but finding what works via blood testing and dietary experimentation is something that we can all do.
@@conqueragingordietrying1797 Yes, for sure. Requires individual attention and strategies. But I appreciate the general direction to go in. Thanks much for doing this stuff!
@@conqueragingordietrying1797 Mind me asking the a general composition of your protein intake? My impression that meats, for example, would lead to raised levels of methionone and then homecysteine levels. So, I'm curious if you eat proteins that cause less of a spike of methionone.
@@reforesters Sure, I don't mind. In terms of animal protein intake, 250g of low-fat yogurt, 80g sardines, ~20g of whey, ~5 eggs/wk, and occasionally cheese are included every day. But, my plant intake is very high (~80-100g of fiber/d, all from whole foods), so that may have something to do with the homocysteine story:
www.ncbi.nlm.nih.gov/pmc/articles/PMC4176105/
@@conqueragingordietrying1797 Thanks!
Doctor I have homocysteine at 50 and I take 5 mg of folic acid. I have the mutated mthfr c677 tt gene. What other things should I take in what dosages? and are there any gene therapies to fix permanently?
Make sure to take methylfolate, not folic acid, particularly since you have a poor MTHFR variant and your body won't process folic acid well. 5mg of methylfolate is likely way too much, though. When you switch, try starting with 1mg/d or less. I have the same variant and I only take 400 mcg/d although after a lot of experimentation I also take riboflavin, methylcobalamin and choline (alpha GPC). TMG / betaine never worked for me - felt awful. I also take creatine and eat a lot of protein. My homocysteine is around 4. See work by Dr Ben Lynch for more info on MTHFR.
@@41hulas82 thanks man
Hi Michael, I'm re-watching some of your old videos....Maybe a higher protein intake lowers homocysteine because it allows your body to make more enzymes that are needed to process homocysteine. Just a guess though.
Hey Just saying, it’s definitely possible, but I’m hesitant to increase protein intake bc the majority of blood biomarkers look good. Serine + B6, without NMN will be the next experiment, which should lower homocysteine.
@@conqueragingordietrying1797 Sounds good. Look forward to the results of serine + B6!
@@justsaying7065 Ha, inside scoop before I put it into a video (sometime soon)!
@@conqueragingordietrying1797 This is a tangent. I'm wondering if the same logic applies to why your NAD is a bit low - it could be that reduced protein intake results in low amounts of the enzymes needed to make NAD. So even if there are enough substrates (i.e. B3), the amount of NAD that can be made is limited by the amount of enzymes available. This could explain why 300mg of NMN didn't increase NAD level.
If I remember correctly, you want to raise your NAD level in order to raise DHEA. Have you looked at the correlation between DHEA and protein intake? If this hypothesis is correct, then you may see a correlation.
@@justsaying7065 No worries, tangents are ok!
Unfortunately, I only have 5 venipuncture tests for DHEA-S, and protein intake for all those tests is in the 95-100g range. I don't have data with higher protein intakes (~145g/d).
Do you feel better?
Would a lower level of methionine also be beneficial to reduce homocycteine?
Because methionine is converted directly into homocysteine, in theory, yes.
@@conqueragingordietrying1797 I also wonder how SAMe fits in... .
WAY over this layman's head. But my homocysteine jumped up to 14 despite large folate and betaine supplementation. I recently engaged creatine supplementation a la Dr. Greger to see if that helps, and I'll be more regular with my B-12. Next blood work is in September.
Also supplementing NMN and resveratrol a la Sinclair for several months prior to last test. I hope that's NOT the homocysteine culprit.
When subjects are over my head, I read/watch them a few times and look up concepts, and after a while, I understand it more. Keep us posted on your homocysteine progress!
My homocysteine was recently
Wow, that's one of the lowest homocysteine's that I've ever seen. Based on the meta-analysis at 13:05 in this video, lower may be better:
ruclips.net/video/du3pjIpoC8Q/видео.html
Alternatively, if you have a lot of other blood biomarker data, you could do a biomarker vs biomarker analysis to see if too low for homocysteine is correlated with an overall youthful phenotype. I've used that approach to discover that too high is possible for albumin and RBCs, for example.
in how much time did u see it drop? i'm doing around 9g of nac and 20g glycine per day
Glycine could be buffering methylation through the production of betaine and that is helping your homocysteine
How about getting your B vitamins through nutritional yeast?
I'm not a fan of its taste, but nonetheless, I'm not deficient for any of the B vitamins.
I think you got it backwards. Homocysteine is likely an affect of, not a cause of inflammation. In many protein expression experiments we use homocystine under specific conditions to help fold proteins - especially for high cysteine containing proteins like cytokines, which can both regulate or drive inflammation - also depending upon conditions. And HS counteracts affects of ROS. Suggest that inflammation is driving an up-regulation of HS to counter inflammatory affects. Look at glutathione levels too if possible. If you drop inflammation then I predict that the HS will also drop. Suggests that you want to work on the inflammation not the HS. This might be something you can measure. Inflammation is up-regulated in aging after all.
Yes, it is possible that homocysteine is a consequence, not a cause.
High likely that you’re right , I can’t get my levels of HS below 10.... and the only thing that gets it below it is Hydrogen rich water ...... a potent anti inflammatory regulator
I seem to have normal crp but high homocysteine… so Nadia does not reduce homocysteine?!😮
On the Protein vs B12 issue maybe methionine has some role as intake generally increases with increased protein but varies depending on protein sources.
Hey Peter, higher protein should increase methionine, which would be converted into higher levels of homocysteine by mass action. So it must be another mechanism...
@@conqueragingordietrying1797 So this is part of the explanation of why red meat is not as healthy as pea protein? Methionine increases homocysteine?
@@iblisthemage I'm not suggesting that at all...Also, I eat green peas occasionally, and red meat rarely, so my data is likely not related to that debate.
Good stuff, thanks @@contentviewer7!
@@contentviewer7 I think it's because Met restriction decreases CBS expression/Met increases it . There's a study on naked mole rats that is interesting by Dzeigelewska et al. 2016; wish I were allowed to post links (YT hates me).
Mine was 16, I have been supplanting with NMN, is that causing my high homocysteine?
I can't say if that's the case for you-I'd carefully track diet, supplements, and blood tests, to see what may be impacting what.
How do you increase the protein intake? Are you supplementing with whey protein or just regular increase of protein from foods?
My whey intake is ~15g/d, and the higher protein is mostly from vegetables, including 500g/d of broccoli, 500g/d cauliflower.
@@conqueragingordietrying1797 it seems you're a TH-17 dominant overmethylator. you could experiment with cheap b-vitamins to get an idea of your endogenous methyl-group production.
@@thenewapollo I don't know if that's true. My homocysteine was lower in my early 30s, so if I was a TH-17 dominant overmethylator, one would predict higher homocysteine levels in my early 30's, too.
@@conqueragingordietrying1797 How so? Why would it be higher? I am only pointing out that you don't need TMG or low protein to metabolize methionine properly, unlike myself.
I think the answer to the age related increase of methionine lies in the adenosine pathway. What changes have you made to keep your adenosine production up?
@@thenewapollo If I had a methylation problem, we'd expect to see it in youth, not just later in life.
I haven't measured adenosine, and I'm not concerned about it.
B12 is hydroponic so thr results could be a delayed response from b12 accumulation
Are you able to shed some light on how the Pfizer Covid vaccine could/would impact on someone with high homocysteine levels and PCOS?
Hey Margie, I haven't come across any data that Pfizer's vaccine affects homocysteine.
Interesting. Would be good to know if homocysteine causes aging or if it is just a marker of aging or even something that is produced by the body in reaction to aging in order to fight it. According to Wikipedia "Typically, hyperhomocysteinemia is managed with vitamin B, vitamin B, and vitamin B supplementation. However, supplementation with these vitamins DOES NOT appear to improve cardiovascular disease outcomes." Wikipedia gives this reference: Martí-Carvajal, Arturo J.; Solà, Ivan; Lathyris, Dimitrios (15 January 2015). Martí-Carvajal, Arturo J (ed.). "Homocysteine-lowering interventions for preventing cardiovascular events". . : CD006612.
With regard to protein lowering homocysteine: maybe the higher protein (glycine) is reducing a bottleneck in the glutathione production process and this somehow lowers homocysteine.
I'd prefer to have relatively lower homocysteine and slow/prevent any age-related increase. It's associated with all-cause mortality and dementia- that it doesn't impact CVD outcomes in RCTs is only part of the story.
What is an optimal b12 result when looking at blood results please?
Hi Little Voice, I haven't done an exhaustive literature review for that yet, so I can't say. It's on my to-do list, though.
@@conqueragingordietrying1797 I was told high levels are a sign of liver inflammation
@@littlevoice_11 Got any papers that show that?
Conclusion: A high-protein, high-methionine diet does not raise homocysteine concentrations compared with a low-protein, low-methionine diet in overweight subjects.
-NIH-
Homocystine increases as glycine depletes,
Perhaps glycine fixes both excess in Homocystine and lacking glutathione....
Protein allows for easier biogenisis of glycine but
Increases cysteine
@Amara Braun I've been trying to source potassium and magnesium from natural sources
Milk thistle does over active the antioxidant response,
I used to use peroxide in college to grow cultures with out air filtration.
Cultures grow, airborne contamination dies....
I don't believe the oxidation is on accident
The lack of antioxidant likely is
@a Braun okay, hope you're doing well
@a Braun yes of course,
What am I really saying and why
Michael: You may be reducing your homocysteine by increasing your protein, but that addition of protein may cause other problems , at least that's implied by some mortality data. . "Adults in the 50 to 65 group who reported a high protein intake had a 75% increase in overall mortality and were 4 times more likely to die from cancer during the following 18 years than those in the low protein group. The moderate-protein diet was associated with a 3-fold increase in cancer mortality compared to the low-protein diet." "In adults over 65, however, a high-protein diet was linked to lower mortality." This data seems to imply that maybe one should wait until around age 65 before increasing protein above lower than average intake. See Protein Consumption Linked to Longevity, March 17, 2014
. Study results were published on March 4, 2014, in Cell Metabolism.
If higher protein was bad for my health, we'd expect to see it reflected in my biomarkers, which are mostly youthful:
ruclips.net/video/G5zXa4DLvjY/видео.html
@@conqueragingordietrying1797 I don't know that biomarkers pick up all associated diet risks and I don't know that better biomarkers always means better health. For example, I can get a youthful homocysteine biomarker by increasing b12. The B12 supplementation may improve my homocysteine biomarker, but according to studies, the supplementation may also increase my mortality and lung cancer risk. , I have also cited one study in another comment above whereby those with higher homocysteine fared a lot better than those with lower homocysteine in terms of stroke risk. This is another instance whereby a better biomarker may not mean better health.
I don't know if plant based proteins would effective or as of effective animal based proteins for reducing homocysteine, but at least they have a better mortality trend. There was an eight percent lower risk of mortality associated with plant protein compared to animal protein. See Diets high in protein, particularly plant protein, linked to lower risk of death, Science Daily, July 22, 2020, reporting on a BMJ article. I can't say whether or not this conflicts with the reporting on general protein intake in Cell Metabolism since the Cell Metabolism article segmented results by age group.
@@jackbuaer3828 Population-based studies are a good start, but it's important to determine whether they apply, based on objective biomarker data, at the individual level.
In this study, those with higher homocysteine fared much better than those with lower homocysteine in terms of stroke risk. They compared three groups Vegetarian (lower B12, Higher Homocysteine), Vegetarian (higher B12, Lower Homocysteine), Non-Vegetarians. Which group do you think did best? The vegetarians with lower B-12 and Higher Homocysteine had the best results. If I am interpreting the study correctly, the vegetarians with higher homocysteine had about half the risk of overall stroke, of meat eaters and vegetarians with higher b-12 and lower homocysteine.. See Vegetarian diet and incidence of total, ischemic,
and hemorrhagic stroke in 2 cohorts in Taiwan published in the journal Neurology.
Does too much B12 supplementation cause lung cancer?
Is there published data for that? Both low and high B12 are associated with an increased risk for cardiovascular mortality in this study:
pubmed.ncbi.nlm.nih.gov/33032595/
@@conqueragingordietrying1797 www.sciencedirect.com/science/article/pii/S1877782115002854
So equal doses of B3 and B12?
I'm not sure about equal doses, but I'm working on an approach where methyl-B12 isn't essential for reducing homocysteine (in my case). Update video is on the list for sometime in March...
@@conqueragingordietrying1797 I take 500mg TMG with 100mg niacin. Haven't test homocysteine level. Also 100mg NAC
Homocysteine has been associated with lower all-cause mortality, but will lower Homocysteine lower mortality risk? According to a meta-analysis of RCTs, the answer is NO ("Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals"). There was no reduction in cancer, CVD, stroke, or all-cause mortality.
Ah, study population is the key point-that data is in people that had an increased risk of cardiovascular disease. The corresponding meta-analysis should examine keeping homocysteine at the lower end of the range in healthy people-are outcomes longitudinally improved/delayed? As far as I know, that study doesn't exist yet. Note that higher homocysteine in my data is significantly correlated with an older PhenoAge, but that's over 8 blood tests. We'll see how it plays out with more data.
I'm still thinking about the LDL paper, stay tuned for that!
Personally b vitamins had no effect. Creatine, choline and glycine did.
On your homocysteine levels?
It sounds like you're taking about 400 times the RDA for B12. Did I read that correctly?
At most, yes, as it was 1000 mcg/d. I've since cut that to 300 mcg/d, but that didn't reduce homocysteine for the last test, so I may have to go a bit higher.
@@conqueragingordietrying1797 Please let me know where you end up. I'll look for a B12 only supplement because my B Complex stress supplement has only 12 mcg and would require about 30 pills per day to reach that level!
@@jamesfortune243 It's not about following what I exactly take, which is guided by the biomarker data. If your homocysteine levels are closer to 5 than 10, then your B12 intake may be sufficient.
@@conqueragingordietrying1797 Fair enough. But your experience points out that it might take a lot of B12 to move the needle if needed.
This is phenomenal work thank you . Now my diet is keto / carnivore with very low carb < 35 grams per day. Essentially no veggies or fruit . What is your diet ? I lost the 40 lbs I needed to lose , , triglycerides dropped from 169 to 87 , HDL 78 of course my LDL is 200 I need to get tested which kind it is …. After ablation they said zero evidence of any cardiovascular 🫀. Disease . Kidney function , damaged by blood thinners has improved to 1,5 creatinine but more to go. So I am sold on Keto as a way of life but we all hear that too much protein is bad etc at 76 you need to eat more carbs all BS I think you have really hit upon a key factor for these diseases
Keep up the good work
He eats a LOT of vegetables. Based on his carotenoids video 416g/d carrots, 134g/d Watermelon and Spinach, 401g/d Broccoli and 314g/d red bell peppers. and that would be just to impact carotenoids, I believe he eats mushrooms as well among other things.
pretty sure his diet is very plant based, he does consume some animal products but almost as opposite to a keto diet.
you need to track your amino acids
I'm surprised there is no mention of methionine. An amino acid higher in animal protein than in plant protein.
There's a circular pathway between methionine and homocysteine. And both are bad in different ways.
Research are beginning to show that methionine restriction mimics calorie restrictions effect on lifespan.
But further research has shown that glycine mimics methionine restriction.
It's like it was glycine deficiency that was the problem,
Some rat research shows that serine and glycine reduces homocysteine.
Al this seems to tell us that supplementiong with glycine should lower homocysteine, and be beneficial for our lifespan.
Needs more research, I'm sure!
We already know that supplementing with large doses of NAC (cysteine) and glycine restores youthful levels of glutathion.
Maybe it also reduces homocysteine to youthful levels!
Hey @larsnystrom6698, there are a couple of methionine restriction videos on the channel, as is the discussion about lowering homocysteine with glycine, which didn't work for me.
I'm a 57 yr old woman and my homocysteine was 8 this year - it's been as high as 11, averages 10. I do take creatine because I work out a lot, and I was also taking a methylated B complex, but my B12 levels were super high, so I'm cutting back on that. How high is too high for B12 levels?
I'm worried about B12 being too high, too.
Plasma B12 levels < 300 pg/mL (see Figure 2) is associated with lowest risk for all-cause mortality, whereas risk is increased above 500:
pubmed.ncbi.nlm.nih.gov/31940038/
How that translates to dietary intake likely is individual, so it's important to measure blood levels.
I'm 42, I was tested last summer, was at 15!
I'm 17 years my homocysteine is at 13 umol/L is it normal or do I need to lower it?
Based on the aging and all-cause mortality data, your 13 is a bit high.
@@conqueragingordietrying1797 My blood iron is normal but my b12 is low will i use 1000mcg of vitamin b12 sublingual methylcobalamin help lower my homocysteine?
This video really addresses an seemingly important piece of medicine. I've wondered why doctors do not routinely test homocysteine. When I tell friends about it they treat me as if I have lost my mind.
I'm curious.. have there been studies that show increased homocysteine negatively effects the blood markers that you track? Or negatively effects epigenetic age?
I've been taking 1000ug tabs of methyl folate. Too much?
Very interesting about the protein intake, btw. It's hard to know what to do. I've read that protein restriction increases lifespan. And yet protein seems to benefit at least healthspan. Hmmm
These are good points, Matthew. There are many biomarkers that can be measured routinely but are not, including Lp(a), insulin, and others, but are not probably to limit insurance costs.
I've looked into Hcy as a marker of epigenetic age, but there are no studies that I know of that have used that in conjunction with the gold standards for epigenetic testing, Horvath's clock, Levine's DNAmPhenoAge, and GrimAge.
Protein restriction does extend lifespan (in mice), but it's more complicated (imo) in people. Too little, and muscle protein synthesis will be limited. Too much, and there may be excessive IGF-1 and higher cancer risk. For me, I use blood testing (BUN) to help sort that out:
ruclips.net/video/u654YTubFRM/видео.html
in terms of too much for methyl-folate, I can't answer that-your data will tell the story. You can measure serum folate, and see if it's high, and then what are the consequences of very high serum folate? Is mortality risk increased, like very high B12?
@@conqueragingordietrying1797 Michael, thank you again for such awesome information. IMO, every blood test should come with links to your work. These little range indicators don't help all that much.
What would be the sweet spot of protein intake for a women ?(28 y.o) i imagine this changes as you age as well?
I'm not in the medical field, my mother was, and my sister and bro in law are. I brought up the vagus nerve once and mentioned gfr once as well and they just look at me weird. The thing is, they aren't stupid either. I gave up
Best B12 source is Meat, Best Protein source Meat again, so clearly shows that as Carnivores, we will better survive if we stick to it
Could it be an increase of Omega-3 ? If your protein is from fish , you may also be elevating your Omega-3 intake. See: "How B Vitamins & Omega 3s Reverse Cognitive Decline" video. Where Head of Pharmacology at Oxford University, Professor David Smith presents his studies on the link between nutrition and the prevention of cognitive impairment and Alzheimer’s disease.: )🍱🍣🗝
Louder
Sorry about that, I’m using a new microphone since then!