Homocysteine: what it is, why it’s bad, and how to reduce it
The last decade has seen a sudden interest in homocysteine, a type of amino acid involved in the breakdown of certain compounds in the body. This interest is largely due to the discovery that elevated levels of homocysteine are a major risk factor for serious vascular diseases such as stroke.
In fact, a study published in the British Medical Journal has revealed that high levels of homocysteine in blood plasma can significantly increase the risk of death from cardiovascular disease in older people - more so than high cholesterol, blood pressure, or smoking.
And that’s not all. Elevated homocysteine is also now linked to migraines, dementia, poor memory function, reduced concentration and judgment, and low mood. Women with high homocysteine levels may struggle to conceive and are at risk of recurrent miscarriage.
Clearly, homocysteine is a serious risk factor for ill health, and something we all need to be aware of.
But what is homocysteine?
Homocysteine is a naturally-occurring amino acid that’s created when your body breaks down the essential amino acid methionine. Methionine is broken down into homocysteine, and then homocysteine is ‘recycled’ back to become methionine again. Methionine is a sulfur-containing amino acid involved in building proteins and producing certain substances in the body, including the antioxidant glutathione and the molecule SAMe.
A host of important nutrients are created throughout the methionine-homocysteine pathway; all of which play a part in various other biochemical reactions such as detoxification, healthy immune function, the formation of connective tissues, as well as brain and cardiovascular function.
The specific enzymes required for this pathway require many important nutrients, especially B vitamins. A lack of any particular nutrient can lead to an undesirable elevation in homocysteine levels. It’s for this reason that the level of homocysteine in your blood plasma becomes an important indicator of overall health.
The metabolism of homocysteine
Normally, homocysteine is broken down by your body’s stores of vitamin B12, vitamin B6, and folate and changed into substances that your body actually needs.
There are two pathways through which the methylation cycle can convert homocysteine to methionine.
- The cobalamin (vitamin B12) and folate-dependent re-methylation pathway that regenerates methionine. This is ‘“long way” around the cycle via the MTR and MTRR enzymes that requires B12 and the forward reaction of the MTHFR (where the C677T impairs the activity) for function.
- The second is a “shortcut” through the middle of the cycle that bypasses MTR, MTRR and MTHFR via the BHMT enzyme. If you think of this portion of the cycle as a clock, the BHMT enzyme can use phosphatidylserine, phosphatidylcholine and TMG as substrates to go directly from homocysteine at 6:00 to methionine at 12:00 skipping 7:00 through 11:00. The use of phosphatidylcholine, phosphatidylserine and TMG therefore help to bypass these mutations. This pathway generates more norepinephrine relative to dopamine.
When this happens properly, there should be very little homocysteine left in your bloodstream.
Research has shown that high levels of homocysteine in your blood may indicate deficiency in B vitamins. In other cases, it may indicate heart disease or a genetic condition.
Why is high homocysteine so bad?
Homocysteine accumulates in the body if the biochemical transformation process is not working properly. This is usually due to a lack of folate, B6, and vitamin b12. If untreated, hyperhomocysteinemia can lead to vascular damage, cognitive impairment, neurological complications, congenital defects, and pregnancy complications.
Raised homocysteine affects the way cells use oxygen, resulting in a build-up of damaging free radicals. Oxidation has already been linked to the onset of numerous diseases of the heart, brain, and immune system. Reactive chemical forms such as free radicals can oxidize low-density lipoproteins, which result in the buildup of oxidized fats and proteins within developing arterial plaques. This oxidation injury - along with methylation defects and impaired DNA repair due to poor folate metabolism - is also implicated in carcinogenesis.
Homocysteine is also shown to stimulate the growth of smooth muscle cells, causing the deposition of extracellular matrix and collagen. Artery walls can become tough and thickened, increasing the risk of cardiovascular disease.
As if that weren’t enough, homocysteine has also been linked to neurodegenerative disorders, particularly in the case of vitamin B12 deficiency.
What is considered high homocysteine?
A normal level of homocysteine in the blood is less than 15 micromoles per liter (mcmol/L) of blood. Higher levels of homocysteine are split into three main categories:
- Ideal: 5-9 mcmol/L
- Moderate: 15-30 mcmol/L
- Intermediate: 30-100 mcmol/L
- Severe: greater than 100 mcmol/L
- Cardiovascular reactions
The tricky thing about hyperhomocysteinemia is that it typically doesn’t produce any noticeable symptoms. Most people will only have their homocysteine levels tested if they appear to have symptoms of a vitamin deficiency.
This is why it’s important to be aware of the signs of deficiency in B12, folate, or both.
Symptoms of B12 deficiency
Symptoms may vary from person to person, but can include:
- Pale skin
- Weak muscles
- Lack of energy and/or fatigue
- Numbness or tingling sensations (similar to pins and needles) in the hands, arms, legs, or feet
- Light-headedness or dizziness
- Mouth sores
- Noticeable mood changes
- Trouble walking
- Lack of appetite
- Weight loss
- Smooth and tender tongue
- Increased heart rate
Symptoms of folate deficiency
Additional symptoms caused by folate deficiency can include:
- Mouth sores
- Swelling of the tongue
- Problems with growth
Other causes of high homocysteine levels
Besides deficiency in folate or B12, other risk factors for hyperhomocysteinemia include:
- Low thyroid hormone levels
- Kidney disease
- Certain medications
How to treat high homocysteine
Vitamin B6 (P5P)
Recommended supplements for lowering homocysteine
Potential Homocysteine Supreme™ side effects
- Vitamin B6 is considered safe in doses up to 100 mg per day. In some people, higher doses may cause nausea, vomiting, diarrhea, stomach pain, loss of appetite, headache, tingling, sleepiness, and other side effects.
- It’s important to note that those who are B6 deficient may have a genetic disorder or problems with the absorption and conversion of pyridoxamine and pyridoxine into the active form pyridoxal 5’ phosphate in the liver.
- Methylfolate may produce side effects in some people, including irritability, difficult sleeping, sore muscles, aching joints, acne, skin rashes, anxiety, palpitations, nausea, headaches, migraines, burning or stinging in the nerves, runny nose.
- Betaine may cause a fishy smell in the breath and bodily secretions in some people, or when taken at high therapeutic doses. However, taking riboflavin (Vitamin B2) at 100mg twice daily appears to eliminate this odor.
- NAC can produce a variety of adverse reactions, but most of these are due to incorrect dosing. High doses may cause nausea, vomiting, diarrhea and constipation. It can slow blood clotting, so it should not be taken by people with bleeding disorders or taking blood-thinning medications.