Inflammation: Excess Homocysteine

Homocysteine is a sulfur-containing amino acid that is an important building block of protein that is produced in the body.

Its produced by another amino acid called methionine. (high sources of methionine include meat, egg whites, and seafood) Its a metabolic byproduct of protein metabolism.

Homocysteine is usually found in very small amounts in your body. That’s because your body converts it efficiently into other products with the aid of B vitamins.

If you have higher Homocysteine levels you may experience the following symptoms:

TESTING FOR HOMOCYSTEINE

A doctor can order a simple blood test to find out if there is a B12, folate, or B6 deficiency. It can be used to check for heart disease for those who are high risk, or help diagnose homocystinuria (a rare genetic disorder). Its not a common test and its relatively expensive and unfortunately rarely covered by insurance companies.

Generally, the homocysteine levels are present in very small quantities in the blood. The normal homocysteine levels vary based on age and gender. However, the standard range of homocysteine is less than 15 mcmol/l (micromoles per liter). The higher levels of homocysteine are divided into the following three categories based on the severity.

• Moderate – 15 to 30 mcmol/l

• Intermediate – 30 to 100 mcmol/l

• Severe – >100 mcmol/l

FACTORS THAT INCREASE HOMOCYSTEINE LEVELS

1. High Protein meals

Sources of Methionine, which convert to homocysteine, are PROTEIN

2. Nutrient Deficiencies

- folate,

- vitamin B6,

-vitamin B12.

Apart from vitamin deficiencies, higher homocysteine levels have been linked to heart disease, cognitive dysfunction, kidney disease and dementia.

Homocysteine is converted into less toxic and more useful amino acids via 2 biochemical pathways. Remethylation and Transsulfuration.

Re-methylation: A methyl group from 5MTHF, a breakdown product of dietary folate, or betaine, is added to homocysteine to convert it back into methionine. Vitamin B12 is needed in this process, as are the enzymes methionine synthase (MTHFR). But it is the enzyme, not the gene.

Betaine (trimethylglycine, TMG) occurs naturally in our cells. Taking Betaine can improve SAMe’ mood benefits. But SAMe generates homocysteine, which can have toxic effects.

Betaine readily provides methyl needed to recycle homocysteine. Betaine bypasses enzyme systems that get methyl from folate and vitamin B12, but are vulnerable to inherited gene errors. Many individuals who are unable to achieve healthy homocysteine regulation by taking folate and vitamin B12 experience success by taking betaine.

Transulferation:

Homocysteine is converted to cystathionine by cystathionine B-synthase. Vitamin B6 is needed for this conversion. Cystathionine can then be converted into cysteine and subsequently glutathione which a really powerful antioxidant which helps your body detox.

When homocysteine can not be converted into other compounds, it builds up in the body. Chronic buildup can eventually start causing damage. So you can see how B vitamins are so incredibly important.

This also holds true for high levels of oxidized cysteine levels. As well as chemokines, interleukens, leukotriens etc…. Where as heparin can inhibit pro-inflammatory macrophases; however, you have to live in The Goldilocks Zone… too much will also cause issues.

Note: Several studies have suggested that people who were on a vegetarian or vegan diet had significantly higher homocysteine levels most likely due to lower B12 levels. Vegan diets can be low in B12, especially if you eat a lot of soy, which will raise your homocysteine levels.

As you can see, nutrient deficiencies hamper the methylation cycles further and these important vitamins and nutrients are essential to healing our inflammation.

You need this process (remethylation and transulferation) to work properly to achieve optimum methylation and glutathione production; because glutathione is your bodies master detoxifier and methylation is the process that makes all of that happen.

3. Smoking Studies have suggested that being exposed to second hand smoke and smoking can increase homocysteine levels.

4. Alcohol consumption can increase homocysteine levels, most likely by lowering Vit b12 and folate levels, additional sulfur compounds and alcohol actually destabilizes cell walls – especially mast cells.

5. Stress

6. Drugs/Pharmaceuticals

Several drugs have been known to increase homocysteine levels

• Methotrexate – an immunosuppressant

• Metformin – used in diabetes

• Cholestryramine, used to lower cholesterol

• Antiepilectics

7. Kidney Disease Kidneys help transform homocysteine into other amino acids. Therefore, a decrease in kidney function can cause an accumulation of homocycsteine. This explains why those with kidney disease have such high homocysteine levels.

8. Hypothyroidism Several studies have found higher homocysteine levels in hypothyroidism.

9. Dental Health Chronic periodontinitis (inflammation in teeth and gums) have been linked to elevated homocysteine levels. The elevated levels return to normal after the periodontal disease is treated.

10. Genetics. Homocysteine levels increase in a rare inherited condition called homocystinuria. If severely elevated homocysteine levels are found, your doctor will usually do more testing to rule out or confirm a diagnosis.

Other than homocystinuria, slight elevations in homocysteine can be caused by a common gene mutations in the every individual has 2 MTHFR alleles (one from each parent). Mutation in just one MTHFR alleles is referred to as heterozygous. Mutations in both alleles is called homozygous. Approximately 10% of people of European decent have 2 mutations in this gene (homozygous).

The most common MTHFR mutations (polymorphisms) found in humans are:

MTHFR C677T (Rs180113). This mutation (the A allele) is associated with reduced enzyme activity, elevated homocysteine levels and altered distribution of folate.

People with one “A” allele for this mutation have 35% lower enzyme activity. And those with both “A” allele (‘AA’ homozygous) genotype have 68% lower enzyme activity.

MTHFR A1298C (Rs1801131). This mutation also impacts the MTHFR activity and homocysteine levels but to a much lesser extent than C677T. Having this particular genetic mutation is easier to restore the body back to homeostasis.

Other genes that can impact homocysteine levels are the genes that encode methionine synthase (MTR; rs1805087) and cystathionine-B-synthase (CBS; rs121964962)

Elevated homocysteine levels are encountered in:

• Sleep Apnea

• Autism

• Gut Disorders

• Heart Disease

• Insulin Resistance

• Depression

• Cognitive Function, Dementia, and Alzheimers

• Autoimmune Disease

• Osteoporosis

• Migraines

On the flip side, low homocysteine can cause issues too. Adequate levels of homocysteine levels are needed for the production of factors that are important for detox (eg glutathione production), such as cysteine, taurine, and sulfate. Thus too low homocysteine levels can also restrict detoxification pathways that respond to oxidative stress. Low homocysteine levels have been associated with nerve damage of unknown cause (idiopathic peripheral neuropathy).

Its important to work with your doctor to find out whats causing your high homocysteine levels and to treat any underlying causes.

How to decrease Homocysteine levels:

1. Healthy organic diet filled with plenty of green leafy foods. Make sure your diet consists of fruits and vegetables high in Vitamin B9 (folate), Vitamin B12, and Vitamin B6.

Note: Its important to note that JUST taking supplements with these vitamins to lower homocysteine levels doesn’t prevent diseases and disorders associated with high homocysteine (such as heart disease, impaired cognitive function, dementia, and osteoporosis) In fact, it can actually be harmful to you.

So in other words, homocysteine is likely a marker of a healthy diet and lifestyle. You have to address all the items in the cycle of illness to improve your health and achieve a happy healthy body.

2. Regular Exercise. Although exercise increases homocysteine in the short term, in the long term it actually lowers it overall to a healthy level. A systematic review of 34 studies found that regular exercise may be able to decrease homocysteine levels. A study in Parkinsons disease patients found that those who regularly engage in exercise had lower homocysteine levels.

3. Manage Stress. Although studies haven’t been able to find a CLEAR link to increased homocysteine levels. I believe its an indirect one seeing stress compromises immune functions, lowers methylation cycles, and can increase histamine levels. Everything appears to be interlinked.

4. Quit Smoking

5. Quit Alcohol Alcohol is chucked full of phosphates and other chemicals that raise homocysteine levels- phosphate alone is toxic to the body and the cheaper the alcohol the more they tend to have. Especially in wine. With methylation impairments this affect is much worse and affects mood and behavior.

6. Some supplements have been found to help decrease homocysteine levels:

- Omega 3

- N-Acetylcystiene (GLUTATHIONE)

- Probiotics (L. Plantarum) Only if you can tolerate it

- Beta Carotene

- Betaine

Controlling your homocysteine levels is extremely important in keeping healthy. With a proper diet, supporting your methylation cycles, getting excercise, and enough rest , and properly managing stress can help keep those homocysteine levels at a proper levels; allowing you to function at optimal levels.

Next paper in this series is; Inflamamtion: Gut Health.

Love and Light,

Happy Healing