Homocysteine is Connected to Mood and Mental Health

Most of you understand that homocysteine is a toxin that, when elevated, increases your risk for heart attack and stroke. This is well-documented, but what is shocking is how dangerous a neurotoxin this compound is! It has been implicated as a contributing factor in neurological and psychiatric disorders such as major depressive disorder, schizophrenia, bipolar, psychosis, Alzheimer’s disease and Parkinson’s. Aggression is another possibility that occurs with hyperhomocysteinemia, the term used to describe high homocysteine in the blood. To clarify for your own knowledge, hyperhomocysteinuria  is when the homocysteine is elevated in urine.

Aggression occurs sometimes in people (even some children with autism) with hyperhomocysteinemia, but it gets treated with pharmaceuticals most of the time because psychiatrists aren’t really trained to evaluate homocysteine which may be measured today via samples of either blood, CSF or urine.

Children with autism, according to the research, have levels of both homocysteine and glutamate in higher amounts than normal reference ranges for children without autism. Reducing these two excitotoxins would be helpful. Even reducing one of them (the homocysteine) would reduce glutamate activity because they are tied together. More on that connection later in my article.

That comes as a surprise to most people because everyone thinks those disorders I just listed are related to dopamine, serotonin or glutamate imbalances. To hear that that homocysteine, which YOU make by the way, is implicated in mental or cognitive dysfunction usually comes as a shock. But again, it’s well-documented.

  • heartbeat irregularities and heart failure
  • stroke
  • headaches (migraines)
  • tinnitus and hearing loss
  • retinal damage and loss of eyesight
  • feeling faint
  • Alzheimer’s disease, Parkinson’s, ALS and other neurological symptoms or diseases

The other shocking surprise I have for you today is that homocysteine can increase in your blood stream if you have mild kidney disease. Your first clue to this might be unexplained itching, or mild swelling in your feet after a shower or prolonged sitting. Did you just say “Ah ha!”

Excessive homocysteine can destroy your life and cause you to get diagnosed with multiple conditions that require expensive medications!

A lot of people walk around with elevated homocysteine and just deal with the symptoms it causes in their body. These symptoms get diagnosed as a new illness, for example, “Parkinson’s disease” or “Dementia” or “Depression.” Then you get prescribed medications that really don’t help that much, all the while the homocysteine is going up and up. Your body is on fire, your head is going to ‘explode’ (ie stroke!) with this pro-inflammatory cytokine and nobody is checking it! A blood test would reveal high levels. Here’s a blood test of one patient who had dangerously high levels of homocysteine, coming in at 24.9. The optimal levels should be closer to 5 or 6, at least in my Functional Medicine circles, so disregard the reference range shown on the sheet below.

There are many factors that cause or contributed to this man’s high homocysteine. He was a chronic user of ibuprofen, thus, his kidney function was impaired and he did have a reduced Creatinine Clearance as a result, along with a benign kidney cyst. Your kidney’s clear homocysteine for you by the way. Also ibuprofen (and about 100 other popular drugs) are powerful, drug muggers of folate, which is B9 and you need that to break down homocysteine. This person has a genetic SNP (mutation) and a medication-induced SNP (ibuprofen) causing his homocysteine to skyrocket. Neurotoxic effects, depression and sudden onset anxiety as well as the expected cardiovascular problems (arrhythmia’s, shortness of breath and weakness) were part of his symptomatic profile.

Here are causes for impaired homocysteine metabolism which leads to elevations. In no particular order:

Impaired methylation. This is the obvious factor, the C677T genetic “methylation” SNP that gets a lot of attention. If you have methylation difficulties, either by mediation or genetically speaking, then you are not making methyl-folate. If you are folate deficient, homocysteine builds up. You can read more about methylation in my article entitled, Methylation Leads to 100s of Diseases by CLICKING HERE. I don’t want to spend time on this right now because I’d rather cover what no one else is talking about. You can read about methylation and homocysteine on everyone’s blog (including mine) so I’m moving on to less obvious reasons for dangerously high homocysteine.

Opiate Analgesics.
If you take hydrocodone, oxycodone and other opiate-derived pain medications, there might be a chance that your homocysteine is significantly higher than it should be. There was a study that showed that users of opiate analgesics had homocysteine levels that exceeded 15. Opiate use (and/or addiction) is a strong predictor of elevated homocysteine. Researchers conclude, “Opium consumption can be strongly accompanied with the elevation of plasma homocysteine concentration, and thus opium addiction can exhibit elevated odds of having hyperhomocysteinemia.”

Now, if you’re in this conundrum because you need pain relief, then all you have to do is consider the vitamins, nutrients and antioxidants to reduce the homocysteine, and just stay on your medication as prescribed. I am absolutely NOT telling anyone to stop any med if it is your physician’s orders and your desire. I’m simply warning people to check homocysteine levels if you’re on opiates, because the drug might be causing other neurological difficulties for you, due to a possible spike in homocysteine.

It’s my favorite NSAID, but it is still a drug mugger of “folate” and therefore, chronic or improper use can contribute to folate deficiencies. As a second issue, it can impair kidney function and it’s your kidneys that clear homocysteine from your body.

Smoking and Drinking.
Not much to say here, these cause free radicals throughtout the body and contribute to heart disease through the release of pro-inflammatory cytokines and DNA damage.

Oral contraceptives.
These pills deplete folate as well as B6, and a deficiency of both of these B vitamins can lead to homocysteine build up. Intestinal problems. If you have a lot of intestinal or digestive problems, or a “Leaky Gut” you don’t have a healthy flourishing gut flora (microbiome). So that means you don’t make proper amounts of B12 due to the lack of gut flora which help you manufacture B12. A deficiency of B12 (methylcobalamin) means you can’t break down homocysteine very well, so it builds up. That impacts your brain. B12 deficiency is a well-documented cause of high homocysteine and remember, this can cause confusion, dementia and major mood swings.

Benzodiazepine withdrawal.
The popular anti-anxiety pills such as alprazolam, clonazepam and others impact the glutamate and GABA receptors in the body. Withdrawal or PAWS (pro-tracted withdrawal) is associated with higher glutamate. With that as your baseline, you might feel more prone to mood swings, anxiety, tearfulness, anger, depression and depersonalization.

Research shows that if your homocysteine is high, it can cause even more glutamate activity (ie problems for you!) by causing glutamate to be even higher. Homocysteine was shown in studies to reduce glutamate uptake in parietal cortex of rodents. If it “reduces uptake” that means it’s floating around causing harm rather than getting absorbed by the cells and broken down.

Evaluating CSF levels of homocysteine is a very important overlooked biomarker for patients with hydrocephalus. Certainly, you could try serum homocysteine levels first, if CSF was too invasive a procedure. RESEARCH from a few years ago showed that high homocysteine correlated with the most resistant, severe types of hydrocephalus. day, Determination of homocysteine, and subsequent treatment might offer hope to patients with this condition.

10 Unique Ways to Reduce Homocysteine

Minimize Meat.
Methionine is the primary building block for homocysteine, so one quick way to reduce the formation of homocysteine, is to cut back on red meat. Red meat gives you methionine. You can almost think of it as “meat-thionine” if you want to help you remember. It’s not a life-long restriction, just a few weeks while you’re bringing your homocysteine down. Reduced methionine means reduced formation of homocysteine. You’re cutting the dragon’s head off with this one.

Ramp up kidney function.
Your kidneys clear homocysteine for you. If they’re not filtering properly and impaired then the homocysteine is going to build up! Take a look at medications that you are using, do they impair your kidney function? Do you have pre-diabetes or yet-to-be diagnosed diabetes? A lot of people do, you can test correctly for diabetes by testing your serum insulin, not your blood glucose. It’s a ratio. Pick up a copy of Diabetes Without Drugs to learn about this, and also natural ways to control or avoid diabetic complications.

Blood donation.
Homocysteine is found in the plasma, which is taken as part of a blood draw. If you are otherwise healthy, free of HIV, lymphoma, leukemia and hemachromatosis, some blood banks will allow you to give a blood donation. There are other restrictions so you should ask your local blood bank or Red Cross center before offering, but I don’t know of one that has refused blood on the basis of elevated homocysteine. A blood donation might take down your homocysteine by a point or two. It’s not a treatment, it’s just part of a quick reduction plan and again, you should be forthcoming and ask at the clinic if they care.

B Complex Vitamins.
These include B6, B12 and B9 (methylfolate). This is what’s needed to break down homocysteine. It works for some people, and it triggers other people and makes them worse. It just depends on many, many factors. Since it is not very simple to get the ratio of B vitamins right, and it’s really hard to hit the nail on the head, I”m moving on from this one. I prefer throwing a “wet blanket” on top of the fire so to speak.

Do you have an FUT2 genetic SNP? If so, you’re short on bifidobacterium. If you eat junk food, you’re also shy on this natural probiotic. Intestinal flora that has healthy amounts of bifidobacterium can help reduce homocysteine. In 2015, in the Journal of Renal Nutrition, researchers noted that patients undergoing hemodialysis had high amounts of E. Coli (bad bug) and reduced amounts of anaerobic bacteria (Bifidobacterium). The scientists gave a capsule of a probiotic containing Bifidobacterium longum (which goes on to produce folate in the gut) and noted a decrease in homocysteine. Pretty cool! CLICK HERE to see the study. You can buy Bifidobacterium-based probiotics, or you can take a multi-tasking formula that contains it.

It’s one of the B vitamins but it’s rarely mentioned in terms of it’s ability to reduce homocysteine. This STUDY published in Circulation shows that high homocysteine is highly responsive to supplements of riboflavin, especially if you have the MTHFR C677T genotype. Diuretics for high blood pressure deplete this nutrient, and so does long-term stress.

In last year’s issue of Food and Chemical Toxicology (May 2017), researchers noted that homocysteine responded to antioxidant compounds found in prune extract. READ the article here. Granted, this was not a human study, but still the prune extract was given by injection and it significantly decreased homocsystiene levels. We can joke about it all day long, but you need to know that the prunes caused increased activity of “S-adenosylhomocysteine (SAH) hydrolase” and NAD(P)H: quinone oxydoreductase-1. This is medical speak to tell you it broke down homocysteine really well.

So eating prunes might have a beneficial effect on homocysteine levels, and besides, it’s a great natural fiber for constipation.

Olive Oil.
Olive Oil does not reduce homocysteine levels just to be clear. It is protective however, by preventing homocysteine from hurting your heart and surrounding blood vessels. In a 2009 STUDY, scientists observed compounds in olive oil and found that they were particularly adept at preventing homocysteine from adhering to monocytes, which are part of the body’s “adaptive” immunity. You want olive oil to protect these monocytes and prevent sticking, otherwise these cells can’t go on to grow up and form macrophages which ‘eat’ foreign invaders that enter your blood stream.

Pomegranate Powder.
New research in Biomedicine and Pharmacotherapy was published in June 2018 that showed how “punicalagin” from pomegranates can protect neuronal DNA in the brain of rodents with high homocysteine. Drinking pomegranate juice might help humans, it’s certainly not going to hurt. Even better, you can buy a concentrated pomegranate powder on Amazon and mix some in water.

High homocysteine is associated with a reduction in catalase enzyme activity all over the body. This means hydrogen peroxide builds up in the body and it’s just another pain-causing cytokine like homocysteine. So if your homocysteine is high, your peroxide is too. Catalase is the liver enzyme humans make and it’s required to break down peroxide and turn it into water and oxygen. There are supplements of Catalase that are available now if this “wet blanket” approach intrigues you.

Hopefully, these methods of reducing homocysteine will help you or a loved one. I’ve listed them because the use of B vitamins doesn’t always work. Some people simply can’t tolerate them, they start to over-methylate, or they get too much B6 and not enough B12, or B9, and so on and so forth. It really presents a challenge to hit the nail on the head. But by thinking big-picture and throwing a wet blanket on the ‘fire’ you can make leaps and bounds in days, literally days! Good luck with this and ask your doctor what’s right for you. If you have any other natural methods to reduce homocysteine that REALLY work, and you want me to add them to my list, please write me at [email protected] (Please limit it to 300 words or less).