Published March 9, 2025
It’s been several weeks since our last newsletter. I’ve written a longer article this week to make up for the lack!
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If you’re a human (you probably are, but you never know with AI these days), then you have homocysteine. The question isn’t whether you have it—it’s how much.
For years, homocysteine has been lurking in the background of medical discussions—sometimes hyped as the hidden culprit behind heart disease and dementia, other times dismissed as a meaningless lab value that doesn’t deserve your attention. So what’s the bottom line? Is high homocysteine a real problem, or is it just another not-so-important blood marker?
The short answer: it matters. But as usual, the “why” is more interesting than the “what”.
The Homocysteine Controversy: Is It a Big Deal or Just a Bystander?
Some researchers love arguing about homocysteine. On one side, you’ve got the it’s just a marker” crowd, who claim that lowering homocysteine doesn’t always reduce heart attacks or strokes. On the other, you have functional medicine and longevity experts, (such as Peter Attia) who argue that high homocysteine is a signal of a deeper metabolic issue that absolutely deserves attention.
So, who’s right? Well, both sides have a point.
Here’s what we do know:
– High homocysteine is strongly associated with cardiovascular disease, dementia, blood clots, and stroke. – this raises eyebrows – deservedly so!
– Homocysteine is involved in methylation, which affects DNA repair, neurotransmitter function, and detoxification.
– Lowering homocysteine with B vitamins* has shown mixed results in clinical trials—some studies show benefit, others don’t.
But here’s the key: homocysteine by itself may not be the molecule that causes all the problems. The real issue is what’s happening behind the scenes—your methylation pathways might be impaired, leading to deficiencies in critical molecules like folate, SAMe, and glutathione. These are really important molecules -everyone agrees this.
Take someone like Peter Attia who has a team of researchers that can look into this more deeply, what does he think? . He recently wrote a bestselling book called “Outlive”
Peter Attia’s Take: Homocysteine as a Warning Sign
Attia doesn’t dismiss homocysteine—he sees it as a red flag that something is wrong in your metabolism. In his book “Outlive”, he writes:
“Homocysteine isn’t the enemy, but it’s a signal that your methylation pathways may be impaired. And those pathways influence everything from neurotransmitter balance to DNA repair and cardiovascular health.”
Translation? If your homocysteine is high, don’t just “treat the number.” Figure out what’s wrong with your methylation pathways.
Nonetheless he does suggest that as a surrogate marker homocysteine can be remeasured after intervention-His target? Keep homocysteine below 9 µmol/L, ideally in the 6-8 µmol/L range. If yours its really high, (in the teens etc) it may be wise to look at your genetics along with your lifestyle and your diet.
The Homocysteine Traffic Jam: How Your Body Clears It
First, think of your homocysteine pathways like a busy highway. When everything is working, traffic flows smoothly—homocysteine gets converted into *methionine or glutathione*, and you never even notice.
But if there’s a problem—say, a *MTHFR mutation (very common), **B vitamin deficiencies, or **poor methylation support—you get a **biochemical traffic jam. Homocysteine builds up, and **everything downstream suffers*.
Your body has two main ways to clear homocysteine:
1. The Remethylation Pathway – Recycles homocysteine back into methionine, which your body needs to make SAMe (S-adenosylmethionine), the master methyl donor. SAMe is a very important , necessary molecule.
– Key nutrients: Folate (aka vitamin B9), Vitamin B12, and Betaine (aka trimethyl glycine).
– Potential bottlenecks: MTHFR mutations, low B12, or poor folate metabolism.
2. The Transsulfuration Pathway – Converts homocysteine into cystathionine, which then becomes glutathione, your body’s most important antioxidant.
– Key nutrients: Vitamin B6 and magnesium.
– Potential bottlenecks: Low B6, magnesium deficiency, or oxidative stress.
– Caution here – even though B6 is important as a backup pathway to help clear homocysteine and create more SAMe – too much B6 has been shown to cause neuropathy (nerve damage).
If either of these pathways slows down, homocysteine piles up—and just like a real traffic jam, this creates inflammation, oxidative stress, and endothelial dysfunction.
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Does High Homocysteine Cause Damage, or Is It Just a Marker?
This is where things get tricky. Is homocysteine itself toxic, or is it just a sign that your methylation cycle is broken?
Some researchers argue that homocysteine directly damages blood vessels, increasing the risk of heart disease and stroke. Others believe the real problem is the lack of folate, SAMe, and glutathione—in other words, high homocysteine isn’t the issue, but what it represents is.
Either way, if your levels are high, you probably should address it.
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How to Lower Homocysteine (and Fix the Underlying Problem)
If your homocysteine is elevated, the goal isn’t just to bring the number down—it’s to optimize your methylation pathways so your body runs better.
Here’s how:
1. Boost Methylation (Remethylation Pathway)
– Folate (5-MTHF) – Found in leafy greens, liver, and legumes. If you have an *MTHFR mutation, use a folic acid (vitamin b9) supplement, or even better methylated B9 (methylfolate)
– Vitamin B12 (Methylcobalamin or Hydroxocobalamin) – Essential for converting homocysteine into methionine. Found in meat, fish, and eggs.
– Betaine (Trimethylglycine, TMG) – Acts as a methyl donor and helps clear homocysteine. Found in beets, spinach, and quinoa. Also purchasable as a helpful supplement.
2. Improve Homocysteine Clearance (Transsulfuration Pathway)
– Vitamin B6 (Pyridoxal-5-Phosphate or P5P) – Needed to convert homocysteine into cystathionine and glutathione. Found in poultry, bananas, and sunflower seeds. Caution – may not be the best as a supplement – since higher doses can causes neuropathy as previously mentioned
– Magnesium – Supports enzyme function in both pathways. Found in nuts, seeds, and dark leafy greens.
3. SAMe Supplementation: The Shortcut
If your homocysteine is stubbornly high despite optimizing your diet, consider SAMe (S-adenosylmethionine). This is the end product of homocysteine metabolism, and supplementing with SAMe bypasses the bottleneck directly. – however this a bit pricey as a supplement and exact dose is a little uncertain. I will likely need to do more research on this avenue.
4. Lifestyle Modifications
Reduce Alcohol Intake – Alcohol depletes B vitamins and disrupts methylation.
Quit Smoking – Smoking increases oxidative stress and worsens homocysteine metabolism.
Exercise Regularly – Physical activity helps improve metabolic efficiency.
Manage Thyroid Health – Hypothyroidism can raise homocysteine, so optimize thyroid function if necessary.
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Final Thoughts: Should You Test Homocysteine?
Most doctors don’t routinely test homocysteine, but if you have:
– A history of cardiovascular disease, stroke, or dementia
– An MTHFR mutation
– Cognitive or psychiatric concerns
– Unexplained fatigue, depression, or neuropathy
…you might want to check your levels.
If yours is high, don’t panic—but don’t ignore it either. Fix the underlying problem, and your body will probably thank you in the long run
FYI cost of the homocysteine blood test at LabCorp is $15 (outside insurance) and can be added to your annual blood work if you wish, just ask.
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