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How to Lower Homocysteine

(Homocysteine, Heart Attack, Stroke, Methylation, MTHFR, TMG, Folate, B2)


What is Homocysteine?

Homocysteine is not seen on a standard blood panel, yet it can be a stroke and heart attack risk factor.

Your doctor can order a homocysteine test which can indicate cardiovascular disease, a rare inherited disorder, or a vitamin deficiency.

Homocysteine, an amino acid, is a chemical your body uses to make proteins.

Typically, vitamin B6, vitamin B12, and folic acid metabolize homocysteine and change it into other compounds the body needs.

Emerging research shows we need riboflavin B2 and TMG (Betaine), as some need much more of these two nutrients to be effective in breaking down or metabolizing homocysteine.

Only small amounts of homocysteine in the bloodstream should be leftover and be showing in blood-tests.

[Related Article: Is Methylation Helping or Hurting Your Health?]

One theory is B6, B9, B12 deficiency is the primary underlying cause of high homocysteine levels.

As an inherited amino acid (methionine) metabolism disorder, homocystinuria or HCU, involves a deficiency of cystathionine beta-synthase. This leaves one with excessively high homocysteine levels because of the inability to breakdown the amino acid methionine.

Blood tests with low B-vitamin levels, heart disease, or homocystinuria are risk factors.

*Previous studies showing B-vitamin supplementation has no effect in lowering risk and mortality have been removed from the NIH database.*

References: [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22.23,24]

MTHFR, Homocysteine, and Methylation

Humans carry two copies of MTHFR, a gene. This gene signals to our body how to create an enzyme that breaks down the amino acid homocysteine.

As with all genes, our DNA code for the MTHFR gene varies. A variant is when part of our DNA sequence varies.

Genetic research is working to identify specific variants that generate sickness and invariably wellness.

C677T and A1298C are the two common MTHFR gene variants attracting the most attention. Approximately 25% of Hispanic Americans, and 10–15% of Caucasian Americans are holding two copies of C677T.

Women possessing two C677T gene variants experience an increased risk for children with neural tube defects. Both men and women with two C677T variants along with elevated homocysteine levels also have increased blood clots risks.

In the vast majority of cases, high homocysteine levels result from much more than strictly two common variants alone. Cholesterol, diabetes, nutrient deficiencies, obesity, thyroid dysfunction, and other lifestyle variables all affect homocysteine levels.

When excessive homocysteine levels are still unexplained, a genetic consultation might be indicated.

For most, supporting a healthy methylation cycle with proper supplements and making lifestyle changes can be sufficiently effective.

Related Diseases

Sleep apnea, GI issues, and autism have been linked to high homocysteine levels and homocystinuria.

We also associate an increase in the risk of the following conditions:

Osteoporosis, heart disease, arteriosclerosis, dementia, Alzheimer’s, and all-cause mortality.

Key Nutrients: (Methyl Donors)

1) Choline (Phosphatidylcholine) (Phospholipids) (Algae/ Krill/ Lecithin)

2) B2 (Some use D-Ribose: Energy/Mood)

3) P5P (B6 Active form)

4) L-Methylfolate (5-MTHF) (Active Folate B9)

5) Methylcobalamin (Active B12)

***A Fully methylated B-complex or a high-quality multi-vitamin can satisfy #2-5***

6) Betaine (TMG):

(Link is controversial: raises LDL, however, along with B2, it is the single strongest science-backed compound.)

(Hair loss can be an unwanted side effect in a tiny subset of users.)

7) DMG:

DMG lowers blood glucose and lipids, while TMG can raise blood lipids. Less of an effect on homocysteine than TMG. Some suggest a triple dose would equate to TMG.

8) S-Adenosyl Methionine (SAMe):

TMG raises SAMe levels, making this one perhaps redundant. Most notable effects on depression and osteoarthritis. However, those with high homocysteine, have low SAMe levels. Studies offer the best evidence to support TMG and B2 as being able to effectively breakdown homocysteine.

Top 5 Super Supplements:

#1) Krill/Algae/Lecithin

#2) Creatine (Especially females and vegans)

#3) Magnesium-Taurate

#4) D3/K2

#5) Bioavailable Curcumin: Superstar homocysteine supplement.

#6) Trace Minerals: Zinc, Copper, Selenium: (High-quality Multi-Vitamin)


Excessive dietary methionine such as meat and dairy nuts, beans, and whole grains such as quinoa exaggerate homocysteine levels. This is especially the case with B-vitamin deficiencies or those with homocystinuria.

Creatine + Phosphatidylcholine

We use up 80% of SAMe, our primary methyl donor, to make creatine and phosphatidylcholine. Taking these two supplements spares SAMe levels and supports methylation. Studies show this is a larger factor with women and those on vegan diets.

Lysine + Niacin

We need enormous amounts of methylation for metabolizing these two. While they are both important and needed in slight amounts, taking larger amounts might mean taking equal amounts of TMG or SAMe to offset.

Do’s (Steps to Healing)

· Dietary fiber (Viscous fiber such as psyllium)

· Leafy greens

· More plant-based for diet percentage

· Small protein meals throughout the day

· Resistance exercise lowers homocysteine

· While keto diets raise homocysteine levels, choline-rich eggs can be valuable

· Keep coffee intake to no more than 3–4/ day

· Consider nightly 5 mg delayed release melatonin

· Intermittent Fasting

Don’ts (Other Contributing Factors)

· Cow-based dairy clogs folate receptors (Goat and sheep do not)

· Folic acid (read labels on all processed food and supplements)

· Chemicals

· Antacids

· Stress

· High-intensity exercise

· Daily alcohol: 2 drinks or more lowers B9/B12

· Smoking and 2nd hand smoke

· Periodontitis (gum inflammation)

· Kidney (vitamin D)

· Hyper/Hypothyroidism

Homocysteine Increasing Medications

If you are struggling with homocysteine, these medications might be affecting your levels:

· Cholestyramine

· Colestipol

· Fenofibrate

· Levodopa

· Metformin

· Methotrexate

· Niacin

· Nitrous oxide

· Pemetrexed

· Phenytoin

· Pyrimethamine

· Sulfasalazine

Enzymes Which can Have SNP’s Affecting Your Health

1) MTHFR: Methylenetetrahydrofolate Reductase [25]

Master methylation gene. Stress response, immunity, mood, inflammation, genetic expression, energy, antioxidants, brain chemistry, cellular repair, detox.

2)COMT: Catechol-O-Methyltransferase [26]

COMT is one of several catecholamine, catechol estrogen, and various drug and catechol substance metabolizing enzymes.

Mood, focus, energy.

(Fast or Slow Metabolism)


(Dopamine metabolism: Catecholamines. Dopamine-Norepinephrine-Epinephrine.)

3)DAO: Diamine oxidase [27]

The key digestive enzyme made in the kidneys, thymus, and the intestinal lining of the digestive tract, which breaks down excess histamine in the body.


(Histamine response, food allergies, and sensitivities. Mast cell disease. Auto-immunity.)

4)MAO-A: Monoamine Oxidase A [28]

One of two side-by-side genes encoding mitochondrial enzymes, MAO-A metabolizes amines, such as dopamine, norepinephrine, epinephrine, and serotonin.

Balances levels of dopamine-norepinephrine-epinephrine-serotonin.

(Fast or Slow Metabolism)


(Mood swings, appetite, carb cravings, addictions, energy, alertness, self-confidence, sleep.)

5)GST/GPX: Glutathione S-transferases/ Glutathione Peroxidase [29]

These two eliminate toxic body compounds such as arsenic, chlorine, formaldehyde, and hydrogen peroxide through the production of glutathione.


(Detox, DNA damage, cancers, autoimmunity.)

6)NOS3: Nitric Oxide Synthase 3 [30]

As a reactive free radical acting as a biologic mediator in an array of processes, including antimicrobial, antitumoral, and neurotransmission actions. We make nitric oxide from L-arginine through nitric oxide syntheses.


(Cardiovascular health, blood pressure, blood circulation, and blood vessel formation. Cognition and mood.)

7)PEMT: Phosphatidylethanolamine N-methyltransferase [31]

PEMT is a transferase enzyme converting phosphatidylethanolamine to phosphatidylcholine in the liver.


(Phosphatidylcholine, cell membranes and liver, bile flow, muscle health, and brain development.)

Final Thoughts

  1. Consider taking a high-quality two-a-day multi-vitamin to divide dosing for b-vitamins.
  2. Consider D3/K2, magnesium-taurate, bio-curcumin, creatine, TMG, krill, or algae oil.
  3. Consider all affecting lifestyle changes.
  4. Consult with a professional when one can still not account for the root cause.


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Your Friend in Health

Mark Stein