COVID-19 and homocysteine

The COVID-19 pandemic has caught the whole world by surprise. Suddenly our lives took a 180 degree turn. We are learning to get used to what people call “the new normal”. We have been dealing with the fear, new rules, and social isolation.

Scientists from all over the world are facing this same scenario of total uncertainty, trying to fight what seems to have become the world´s most publicized enemy.

The problem is that everything´s still very recent and although we have made great progress since the discovery of the virus, there are still a lot of things that we don´t know.

COVID-19 seems to affect all groups, however higher mortality rates are observed amongst the elderly, and people with comorbidities such as hypertension, diabetes, cancer, and cardiovascular diseases(1).

Some authors believe that obesity should be considered a risk factor since it was previously associated with increased mortality in patients with H1N1. 

This is because obesity is associated with decreased respiratory capacity and lung function. 

Moreover, the increased inflammatory cytokines associated with obesity may contribute to the increased morbidity in obese COVID‐19 patients(2).

That is one reason why researchers are investigating the role of nutrition on COVID-19 susceptibility and long-term consequences. 

Obesity can be associated with the Western diet which tends to be high in saturated fats, refined carbohydrates and sugars, but low in fiber, unsaturated fats, and antioxidants.  

Consuming high amounts of saturated fatty acids can impact the immune system’s response, making it harder for the body to fight and kill viruses. 

Besides the fact that consuming saturated fats leads to an inflammatory state, including in the lungs, which could contribute to COVID-19 pathology(2).

That´s why at times like this we need to look more closely at our food habits, especially the nutrients we eat. Several nutrients help in the functioning of our immune system. 

As an example, we have vitamins A, B6, B12, C, D, E, and folate(3).

The B-Complex vitamins play an important role in our body. They help to maintain the health of the red blood cells, aid in the functioning of the nervous system and participate in the synthesis of our genetic material(3).

For example, deficiency in B12 can lead to anemia, neurological problems, and even cardiovascular diseases. The latter is due to B12 involvement in homocysteine metabolism(3).

Vitamin B12 can be obtained from food, the sources are fish, meat, poultry, eggs, milk, fortified cereals, and B12 supplements. 

However, not everyone consumes the recommended daily amount they need. Moreover, some people can´t absorb nutrients properly, or simply have a higher requirement of this nutrient, such as elderly people, kids, those with genetic mutations, and pregnant woman(3).

Folic acid (the synthetic form of folate, or vitamin B9) can be found in leafy green vegetables, fruits, dried beans, peas, and nuts, enriched bread, cereals, and other grain products.

Vitamin B6 sources are animal protein, breads, wholegrain cereals, milk, vegetables, and fortified foods. These two vitamins also participate in the metabolism of homocysteine(3).

Homocysteine (Hcy) is a type of amino acid, the building blocks that are used to build proteins. Homocysteine is produced by a process called demethylation (removal of a methyl group (CH3) from a molecule) of the amino acid methionine. 

Methionine is one of the 11 essential amino acids which means our body can´t produce it and we have to get it from our diet, especially from animal protein sources(4).

When a methyl group is added to a methionine molecule, we have the production of homocysteine. For this reaction to occur, we need the help of another type of protein, an enzyme named methionine synthase(4).

Three other components also have an important role in this process: vitamins B6, B12, and folate. In general, when the levels of those vitamins are low, we have an increase in Hcy levels.

Deficiencies in these vitamins, together with genetic factors affecting enzymes involved in Homocysteine metabolism can lead to an increase in Homocysteine levels in the blood. When this happens, the blood vessels become irritated, and the consequences are abnormal clotting and increased risk of cardiovascular diseases.

Hyperhomocysteinemia (high levels of Hcy in the blood) is linked to atherosclerosis (hardening of the arteries) which can lead to a heart attack or stroke, and also to arterial thrombosis and venous thromboembolism. 

Other health problems that have been associated with hyperhomocysteinemia are osteoporosis, dementia, and Alzheimer's.

A doctor may request a homocysteine test when she/he suspects a vitamin B12 or folate deficiency, when the patient has a family history of cardiovascular diseases(4) or even when the patient has a known MTHFR genetic variant.

Homocysteine levels can increase with age, overuse of tobacco, and the use of certain medications. People with hyperhomocysteinemia may benefit from the supplementation of folate and vitamin B12(4).

One of the main challenges in the context of the new coronavirus disease is to find biomarkers that will help healthcare professionals better identify patients with an elevated risk of progression(5).

People who suffer from cardiovascular diseases are more likely to develop severe symptoms of COVID-19. These patients have higher a chance of needing intensive care treatment and even dying from the disease. 

This is because the virus can cause damage to the cardiovascular system resulting in injuries to the heart muscle, arrhythmias, myocarditis, and shock(6).

It is well-known that elevated levels of homocysteine in the blood increase the incidence of damage to the vessels. High levels of homocysteine can also stimulate atherosclerosis and increase the risk of thrombosis(7).

Some authors believe that homocysteine levels should be measured in patients with COVID-19 to assess the risk of cardiac and pulmonary complications. 

They support the idea that it is a simple test that could be made at the time of hospitalization or diagnosis(5).

One study carried out with 273 COVID-19 patients aimed to investigate the potential parameters associated with imaging progression on chest computed tomography (CT). 

This exam uses x-ray equipment to search for abnormalities and to help in the diagnosis of cough, shortness of breath, chest pain, fever, and other chest symptoms(5).

Currently, the PCR (polymerase chain reaction) is the gold standard in the diagnosis of the new coronavirus, and the CT is used to help in this diagnosis. 

The most common findings in the CT exam of COVID-19 patients are pulmonary ground-glass opacities (a pattern that is observed when the lungs are sick), vascular thickness, and consolidation (when the air that normally fills the airways in the lungs is replaced with fluid)(8).

In some cases, both lungs are affected and CT can be used to assess the severity of the lung involvement in COVID-19. The alterations can progress very quickly, with CT exam showing an enlarged and increased extent of ground-glass opacity and consolidation(8).

The researchers investigated which factors could help predict this chest CT progression in patients with COVID-19 in an attempt to find proper biomarkers(5). 

They observed that chest CT progression occurred one week after admission to the hospital. The majority of these patients were older when compared to those who didn´t progress(5).

In patients that had their blood tested for homocysteine levels, it was observed that those levels were higher in patients who had progressed imaging(5). 

This is an important finding because chest CT progression is indicative of more severe disease. Learning how to identify the patients at risk of progression will help healthcare professionals to take quick actions and provide better treatment for these patients(5). 

So essentially this gives us an important clue – high homocysteine may be an indicator of those who could have a harder time fighting COVID-19 if it’s contracted.

As we discussed earlier and in other articles, elevated levels of homocysteine can be toxic for our bodies. The role of homocysteine in coronavirus is not yet well understood. 

However, there´s evidence that high homocysteine levels are associated with other infectious diseases caused by viruses such as HIV, hepatitis, and HPV(9).

 Thus, hyperhomocysteinemia might be one of the mechanisms involved in the progression of the disease.

Since increased levels of homocysteine in the bloodstream can be associated with a worse prognosis of COVID-19, taking measures to reduce your homocysteine levels is likely a good idea.

One of the possibilities is to change your diet. If you have a vitamin deficiency, you can increase your vitamin B12 and folate intake. 

This can be done by simply adding vitamin B-rich food to your meals, things such as green vegetables, orange juice, and beans.

Some people may have more difficulty obtaining an adequate amount of these vitamins through diet alone. Unfortunately, not everyone can solve these challenges with a healthy diet, especially older people who suffer from malnutrition for a variety of reasons such as tiredness, the difficulty of access (fixed incomes), and poorer digestion. 

We know that older people are amongst the group with a higher risk of developing severe symptoms of COVID-19. That´s why it may be helpful to take vitamin B supplements – specifically folate, B12 and B6.

When you eat food containing vitamin B9 or food enriched with synthetic folic acid, the folate present in fortified foods, a perfect body should metabolize it into L-methylfolate for cellular absorption and health benefit.

However, over half of the population has a common mutation in the specific genetic pathway that is responsible for this conversion, it’s referred to as MTHFR. 

And the characteristics of this mutation are not only low folate absorption, but also high homocysteine levels. It is understood that when you consume L-methylfolate in its direct form, you´re already getting the most “usable” and “active” form of vitamin B9 that your body can immediately absorb AND use to normalize those otherwise high homocysteine levels. 

That means your body won´t have to take additional steps to metabolize the folate and the folate will start balancing those homocysteine levels for optimal health.

One important study showed that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes, which can also help to prevent the occurrence of cardiovascular complications(10). 

So taking L-Methylfolate directly improves your cardiovascular health in addition to boosting your immune system and both of these seem to be key indicators in helping you prevent and fight COVID-19.