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Homocysteine: What Is It and Why Is It Important? – MaxWell Clinic

good evening i’m dr david ferris one of

the physicians at maxwell clinic

and it’s my pleasure to host

this month’s

group visit

tonight we’ll be talking about

homocysteine

what it is and why it’s important

so

i want to address uh three different

aspects of homocysteine this evening

first what is homocysteine

uh second what effect does elevated

homocysteine have on health

and with particular attention to

cardiovascular health and brain health

and then if elevated how does one lower

his or her homocysteine

so let’s look first at

what is homocysteine

well homocysteine is an amino acid that

is normally found in the body

you may recall from your high school or

your

college biology that amino acids are the

building blocks of all proteins

every protein of every type

is constructed by through a combination

a linkage of various amino acid building

blocks so homocysteine

is

one amino acid

and

normally in the body homocysteine is

converted to two other amino acids that

are essential for good health

to cysteine

and methionine

but when this conversion is impaired

homocysteine levels build up in the body

and that can cause issues which we’re

going to talk about

in in some detail

a couple of other facts about

homocysteine and and why elevated levels

are important

um i mentioned that homocysteine is

normally converted to these two other

amino acids cysteine and methionine

methionine is particularly important

because it uh it plays a key role in the

generation

of molecules that we call methyl groups

if you’ve had organic hist organic

chemistry you know that methyl groups

are comprised of one carbonite atom and

three hydrogen atoms

and these methyl groups are required for

the

synthesis of dna for the repair of dna

and the dna in our bodies is under

constant assault

from

um

from free radicals that are generated

through normal

metabolism in the in the cells through

from radiation

from various chemical toxins in the

environment so it’s very important that

we have adequate levels of methionine

in the body

to

support

this

this methylation this dna

repair

so there are a number of causes of

elevated homocysteine

one of those can be a deficiency of

folate and other

b

vitamins in the diet

we’ll talk a bit more about this in a

few minutes

but the

key enzyme

that converts homocysteine

into cysteine and methionine is very

dependent

on having

access to adequate b vitamins in order

to function properly so if there’s a

deficiency of folate

and other b12 vitamins in one’s diet

this can contribute to elevated

homocysteine levels

we also see elevated homocysteine levels

in some patients with kidney disease

that have renal failure

it can be seen in patients with low

thyroid hormone levels

and some patients with psoriasis

a skin condition

and there are certain medications such

as anti-seizure

medications and methotrexate

a

a chemical that is used in cancer

treatment and also

often to treat

autoimmune diseases such as rheumatoid

arthritis

these medications can also contribute to

an elevation in homocysteine

a major cause of elevated homocysteine

though in a significant number of

individuals

is is a genetic uh variant

in a key gene that governs

this enzyme

called methylene tetrahydrofolate

reductase i know it’s quite a mouthful

or abbreviated mthfr

this is the key enzyme that i mentioned

that converts homocysteine into cysteine

and methionine

so

some individuals in the population it’s

not uncommon at all

have a genetic variation

that uh decreases the efficiency of this

uh this enzyme that converts

homocysteine into cysteine and

methionine and we’ll come back to talk

about that again in a few minutes when

we talk about how do we treat how do we

lower

elevated levels of homocysteine

we also know that homocysteine

increases with age so as we get older

homocysteine levels can tend to increase

and homocysteine levels may also be

affected by things such as cigarette

smoking alcohol

consumption

and a

sedentary lifestyle

all right so with that is background

about homocysteine what it is and why

it’s important

i want to i want to go further about why

it’s important and what kind of impact

it has on various organ systems

so here you’ll see a diagram i’m sorry

it’s not in color but it’s not this

comes from um

a major review article on homocysteine

uh by tinnelli and uh his colleagues in

frontiers of nutrition from the april

2019 issue but i think it illustrates

well

why we’re concerned about homocysteine

and why we want to try to optimize

uh its level

when when it’s elevated in the body

so you see

the the the big

uh tag at the at the top of um

above the

molecular

structure of homocysteine there in the

middle

titled the cardiovascular system

and this is a a major system of the body

that there are number of correlations

between elevated homocysteine and

cardiovascular disease

we know from a number of studies that

elevated homocysteine levels

promote

atherosclerotic lesion progression

and are associated with atherogenesis so

that’s a fancy way of saying

that elevated homocysteine can

contribute to the development of

atherosclerotic plaque in the coronary

arteries and in other arteries of the

body

elevated homocysteine

also inhibits the production of a

substance called nitric oxide

nitric oxide is an important chemical

that is produced by a healthy

microvascular system by a healthy

endothelial lining

of the vasculature particularly the the

arteries and nitric oxide is a potent

vasodilator

and so it’s very important that

our arteries and other vessels are able

to dilate as needed to meet the body’s

needs and they can only do this if there

are

adequate production of nitric oxide and

that’s very dependent on a healthy

microvascular system

and as i said elevated homocysteine

inhibits the production of nitric oxide

there’s also a correlation between

elevated homocysteine and elevated blood

pressure

elevated homocysteine is a confirmed

coronary artery disease risk factor

so your risk goes up for coronary

artery disease with elevated

homocysteine

and elevated homocysteine has also been

found to be an independent risk factor

for stroke

so again more reasons why

we want to

make sure that homocysteine levels

aren’t extremely high and optimized

whenever possible

let’s move on to

the brain

so this is the other very important

organ that’s impacted by elevated

homocysteine

we know that elevated homocysteine from

what we just said damages the walls of

arteries and that includes the arteries

and the microvascular blood supply of

the brain so if that’s impacted that’s

damaged then it makes sense that

our brains are not going to function as

we want them to function

a researcher named sashdev and his

colleagues found in a study

that elevated homocysteine increases the

risk of vascular disease especially

small vessel disease which can lead to

brain atrophy that is an actual

shrinkage of of the brain

another researcher fung

and his colleagues found that elevated

homocysteine is associated with impaired

cognitive performance and increases the

risk that one has for cognitive decline

and dementia

fung and his colleagues also found that

there’s an associated as i’m sorry an

association between elevated

homocysteine and decrea decreased white

matter in the brain

uh there are two types of matter on a

gross anatomy basis uh in the brain

there’s gray matter

and white matter gray matter actually

the the the neurons the neuron cell

bodies

uh dendrites and

the axons the connecting lengths of one

neuron to another

comprises the white matter

and so

if there is elevated homocysteine that

has been associated with

actually

decreased white matter in the brain

which impacts brain function

a researcher named nelson and his

colleagues

found that and concluded that

homocysteine

actually uh can be neurotoxic

and can consequently adversely affect

memory performance it can damage the

neurons of the brain which are the

the the essential

uh types of cells um that are found in

the brain and and brain function depends

on

elevated homocysteine uh has been shown

to play a role

in the development of various diseases

affecting the nervous system so this

includes stroke

parkinson’s disease alzheimer’s disease

multiple sclerosis and epilepsy

and elevated homocysteine results in the

production of reactive oxygen species

sometimes better known as free radicals

which also can directly damage the

neurons in the brain

all right let’s move around clockwise

to some of the other organ systems that

elevated homocysteine

impacts the next is sensory organs

elevated homocysteine has been

associated

in cases of sudden hearing loss

and elevated homocysteine

is been found to be a risk factor for

age-related macular degeneration

the macula is that very specialized part

of the retina that is most sensitive and

that

we depend on

to

when we focus on something

when we

um to do any kind of close work detailed

work to read

um

it’s it’s absolutely essential that we

have a healthy macula and in some

individuals there’s a genetic component

to this

but uh particularly as they age as they

get into their 60s 70s 80s and beyond

there can be gender degeneration of the

macula

which leaves the these individuals uh

severely constrained in their ability to

to see

at best they increasingly have just some

peripheral vision they may be able to

navigate

around

but

or see things kind of out of their

peripheral vision but anything that they

would ordinarily focus on

to read to watch television to work from

a computer increasingly becomes

compromised so it’s an important

disabling condition

and elevated homocysteine has been found

to be a risk factor for helping promote

that

if we move next to the reproductive

system

elevated homocysteine during pregnancy

has been associated with placental

vascular damage and that can result in

spontaneous abortion and a condition

called preeclampsia

which is a very dangerous condition that

can affect uh pregnant women

uh typically in the

the latter trimester of

of of their pregnancy

and when it occurs can require immediate

medical intervention

elevated homocysteine can also

help contribute to

gestational diabetes

women who while they are pregnant they

don’t have diabetes they don’t have

elevated blood sugar when they’re

non-pregnant but when they’re pregnant

they they develop elevated blood sugars

which does place them at high risk

next moving around uh is the endocrine

system

there appears to be a correlation of

elevated homocysteine with

diabetes complications

and we know that patients with

microalbuminuria

small amounts of albumin in their urine

and proliferating retinopathy which is a

com is a complication

of diabetes

patients with this have been

demonstrated to have homocysteine levels

significantly higher than those of

patients without those complications so

we don’t know specifically whether the

homocysteine actually causes

these things

but

it certainly is is correlated it’s

associated with it

next moving around um

this this circle uh the skeletal system

elevated homocysteine is associated with

an increased risk of osteoporotic bone

fracture

so osteoporosis is a loss of

mineralization

in the in the bones particularly it

impacts

the hips and the femur

and affects the vertebral

bodies of the spine

and this can lead

with progressive osteoporosis

to uh fractures in the verdebral bodies

particularly the

lumbar vertebral bodies and in the

um the hip

which

moving around finally to

the adrenal system the kidney

as renal function decreases we know that

homocysteine levels

increase

and in fact in one case control study

85

of hemodialysis patients had

homocysteine levels above the 95th

percentile of the control group so

there’s a very strong

association there

so i i think you can see from our

walking around this diagram

certainly the cardiovascular system

heart health brain health

are very important but a number of other

organ systems are involved as well

when it comes to elevations in

homocysteine

so

um all that’s fine and good

but if elevated how does one lower it

and so i should say here

that um

virtually all new patients at maxwell

clinic as part of their initial new

patient

laboratory workup

have their homocysteine measured

and

you may have noticed if you’ve seen your

own lab reports with the homocysteine

test results

that

i think labcorp has a normal range or

what we call a reference range of 0 to

about 15.

um

we don’t think that that’s optimal if

it’s certainly in above 10 to 15

we think optimal levels are probably in

the

seven to eight range or lower

and certainly we’d like to see all of

our patients lower than than 10 if

possible

is homocysteine levels increase into the

20s 30s and there’s some very few

patients that’s relatively rare can even

have homocysteine levels uh of a hundred

or or more and certainly the higher the

homocysteine level the the greater the

risk

but let’s talk uh finally

about what do we do how do we address

um

elevated levels of homocysteine when

when that’s a finding

so we we’ve already talked about

how the conversion of homocysteine

to cysteine and methionine is dependent

on a key enzyme methylene

tetrahydrofolate

reductase are abbreviated mthfr

and this enzyme requires

b vitamins b12 b6 and particularly

folate

in order to function normally

so

um

in

individuals that are deficient in b

vitamins especially folate in their diet

this can result in elevated

homocysteine levels

so what are some of the foods

that it’s important sources of folate

well fruits and vegetables especially

green leafy vegetables

uh folate fortified breads and cereals

because of the risk of low folates and

in particularly in pregnant women the

development of um

neural

tunnel defects

in the in the

in the developing baby

then a number of cereals and breads have

have been fortified uh with folate to

put additional folate into the diet what

i meant to say was neural tube

defects

so things such as spina bifida

uh would be an example of that

um

other foods that are rich in folate are

lentils chickpeas asparagus spinach

and in most legumes most beans

but dietary sources may not be

sufficient

in in many patients and so that’s where

often what we will do is certainly

encourage

our patients with elevated homocysteine

levels

to um to to eat a healthy diet and one

in which they’re going to eat the foods

i just mentioned

uh but many times that’s that’s not

enough or it’s not consistent

and so we will supplement with a mixture

of b vitamins uh that is a b vitamin

complex

one of the the primary supplements we

use at maxwell clinic

is creating health gene protect which is

a mixture of b2

b6 b12 and folate so it’s it’s a b

vitamin complex

and when we

uh start an individual on this typically

it may be one capsule a day or often one

capsule twice a day we’ll start

and then we’ll recheck the homocysteine

level a couple of months later

and usually we see a very good response

and the homocysteine level will come

down

to certainly less than 10 and often to

you know that optimal range of seven or

eight somewhere in that range or even

even lower

uh and when that happens uh you know we

we’ve achieved that that optimal range

that that we’re seeking

in some individuals with uh much higher

levels of homocysteine say homocysteine

in the 20s or 30s or higher

we will use a product called folify er

for extended release

this is a much higher dose of folate

and

so in in some cases where we we need to

get much higher doses of folate

we’ll use uh volify er but the vast

majority of our our patients respond

very well to uh creeding health gene

protect

and the reason as we’ve already alluded

to that it’s called gene protect is

because of the importance of

homocysteine

in this uh methionine

biochemical pathway

and and making sure that we have

sufficient levels of methionine

in order to

to produce that dna repair that each of

us continuously needs

so

that’s uh probably more than you wanted

to know about homocysteine

why we think it’s important to measure

it

and and why we pay attention to it uh

but i hope this has been helpful to

provide some some more detail

and

i’m going to

stop my

screen share for the presentation

and see if uh if there are any questions

that i can try to uh to answer

so um i don’t see any uh any questions

uh i hope this has made sense to you and

has been been helpful

so if there are no open

questions

then thank you for attending i

appreciate your attendance and

have a have a really good evening take

care

homocysteine ​​and heart health

Cholesterol, triglycerides and blood sugar levels are most commonly measured to assess cardiovascular risk. But you can also add such an indicator as homocysteine ​​to them. But what is the role of vitamin B9 in this?

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Numerous studies have found an association between high blood levels of homocysteine ​​and a higher risk of cardiovascular disease (especially heart attack), as well as a higher risk of cognitive decline.

Article content

What is homocysteine?

Homocysteine ​​is an amino acid that is an intermediate in the conversion of the amino acid methionine to cysteine. These transformation reactions occur due to cofactors vitamins B6, B9, B12. Therefore, with a lack of these vitamins, the level of homocysteine ​​rises. We do not get homocysteine ​​from food, but we consume its precursor, methionine, from meat, eggs, fish, and dairy products.

Why does homocysteine ​​increase?

Hyperhomocysteinemia is an elevated level of homocysteine ​​in the blood, above 15 µmol/l. According to some data, exceeding the level of homocysteine ​​of 8 µmol/l is already considered as an additional risk of cardiovascular diseases.

A lack of B vitamins will lead to an increase in the level of homocysteine ​​in the blood. Their shortage can be caused by:

• Nutritional factor. Insufficient consumption of foods rich in group vitamins will lead to a decrease in their concentration in the body
• Genetic factor. Enzyme disruption can interfere with the conversion of homocysteine ​​to other amino acids.

Smoking, stress, kidney disease also have a significant effect on the increase in the level of homocysteine ​​in the blood.

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Homocysteine ​​and the risk of cardiovascular disease

Atherosclerosis is the process of deposition of cholesterol plaques on the inner wall of blood vessels. This is one of the main risks of developing cardiovascular diseases.

An increased level of homocysteine ​​”scratches” the vessel wall from the inside, as a result of which it becomes inflamed and atherosclerotic plaques are deposited on it much more easily. High levels of homocysteine ​​may also affect platelets and increase the risk of blood clots; however, the question of whether high homocysteine ​​levels actually cause cardiovascular disease has yet to be resolved. High homocysteine ​​is only one of a set of risk factors.

There is also an association between high levels of homocysteine ​​and complications during pregnancy: preeclampsia, miscarriage and early termination of pregnancy.

Homocysteine ​​control

Eat foods rich in vitamins B6, B9, B12. Vitamin B9 (folic acid) has a particularly effective effect. The daily dosage is 400-600 mcg. Foods rich in vitamin B9 (per 100 g):

• turkey liver (677 mcg)
• dried chickpeas (557 mcg)
• beef liver (290 mcg)
• peanuts (240 mcg)
• fresh spinach (194 mcg)

Reducing foods high in animal protein may also help lower homocysteine ​​levels. It is recommended to focus on protein sources such as fish, beans, whole soy and dairy products.

Although there is little evidence to support the clinical benefit of lowering blood homocysteine ​​levels with vitamin supplements, there are other benefits of eating foods rich in vitamin B.

What Folic Acid Is For – MyGenetics Blog

Folic acid and its derivatives are water-soluble vitamins that are essential for cell growth and reproduction. Folate (vitamin B9) is a general term that applies to a large group of compounds that have a similar structure and vitamin activity. Folates play an important role in the synthesis of nitrogenous bases – the main component of DNA – the carrier of genetic information.

Folate deficiency primarily affects actively dividing cells, especially cells of the bone marrow and the mucous membrane of the gastrointestinal tract (glossitis, diarrhea, other digestive disorders). People who do not get enough dietary folic acid can develop megaloblastic anemia, which causes unexplained weakness and fatigue. It is especially important that the body receives a sufficient amount of this vitamin during the period of active growth (children, adolescents), as well as during pregnancy. In this case, it is advisable to start taking folic acid in advance, even during pregnancy planning.

Discovery history

Natural folates were first discovered 90 years ago in a yeast extract. Yeast extract has been shown to prevent the development of megaloblastic anemia and can be used to treat it. Folates were first obtained in 1941 from spinach, and their name comes from the Latin word folium (leaf). In 1943, folic acid was synthesized – a synthetic fully oxidized form that is not found in food.

Folic acid derivatives were originally used to treat anemia. At the same time, excessive folate intake has been found to enhance the growth of pre-existing tumors, and folic acid metabolism has become a promising target for anticancer drug development. In the 1940s, the antimetabolite of folic acid, methotrexate, was synthesized, which took its place in the treatment of tumors and autoimmune diseases. The drug is widely used today.

Need for folic acid

An increased need for folic acid occurs during pregnancy (especially if there have been cases of fetal neural tube defects before) and lactation, as well as against the background of celiac disease, a condition after resection of the organs of the gastrointestinal tract, with diseases of the liver and / or kidneys, with a high level of homocysteine in the blood, with the carriage of polymorphic variants of the genes of the folate cycle enzymes. Taking certain drugs (anticonvulsants, cytostatics) can lead to an increase in the need for folic acid.

Functions and biochemistry of folic acid

Folates are required for the metabolism of amino acids that make up the proteins of our body, the synthesis of purines and pyrimidines, and DNA methylation. Purines and pyrimidines are the main components of DNA that are needed for doubling its molecules (replication) during cell division. Folate is also needed to correct replication errors, a process called DNA repair, which, together with DNA methylation, is important in protecting the body from the formation of tumor cells.

Folic acid deficiency in the diet of a pregnant woman leads to the risk of severe neural tube defects in the fetus. This pathology was quite widespread earlier, but now, after the introduction of prophylactic folic acid intake during pregnancy, it has become much less common. However, some people are still likely to develop a folate-deficient condition, as there are some metabolic genetics that may require special attention to the folate content of the diet. One of these factors is the carriage of certain variants of the MTHFR gene.

MTHFR is a key enzyme in the folate cycle.

Derivatives of folic acid, after entering the body and processing by enzymes in the intestine through special carriers, enter the bloodstream, and then into the cells. Further, in many cells of the body, folic acid metabolites are included in the so-called folate cycle. In this cycle, folic acid derivatives undergo a series of transformations with the participation of a large number of enzymes and vitamins as cofactors (B2 – riboflavin, B6 – pyridoxine, B12 – cyanocobalamin).

MTHFR (methylenetetrahydrofolate reductase) is a key enzyme in the folate cycle. Due to the presence of several genetic variants of the enzyme, the activity of the MTHFR enzyme can vary from person to person. Depending on the genetic variant, enzyme activity can be reduced by 30–70%. When MTHFR is ineffective, an increase in the level of homocysteine, one of the intermediate products of the folate cycle, is observed, with a high content of this compound in the blood, a number of adverse consequences are observed (cardiovascular diseases, pregnancy complications). Carriers of variant alleles of the MTHFR gene need to control the level of homocysteine ​​in the blood in order to avoid the negative consequences of its excess.

If the level of homocysteine ​​increases, it is recommended to increase the intake of foods rich in folates, as well as vitamins B6, B12; the issue of prescribing synthetic folic acid should be considered by a specialist. It is especially important for carriers of variant alleles to monitor the level of homocysteine ​​during pregnancy.

You can find out which form of the enzyme is present in your MyGenetics tests.

Homocysteine ​​metabolism and pregnancy

Homocysteine ​​is an amino acid, an intermediate product of methionine metabolism. In case of disturbances in the functioning of the folate cycle enzymes, as well as in the deficiency of vitamins B6, B9, B12, homocysteine ​​is not processed efficiently enough and therefore accumulates in the blood.

Elevated levels of homocysteine ​​in the blood are thought to have a damaging effect on the walls of blood vessels, resulting in impaired circulation in small vessels. Very often there is an increased level of homocysteine ​​in diseases of the cardiovascular system (heart attacks, strokes, coronary heart disease), with a tendency to thrombosis (hypercoagulability). Appointment of vitamins B6, B9, B12 effectively reduces the level of homocysteine ​​in the blood.

High levels of homocysteine ​​in the blood during pregnancy can interfere with blood circulation in the placenta, which leads to an increased risk of miscarriage, premature birth, and fetal growth retardation. There are also violations in the blood coagulation system, up to 50% of women during pregnancy have post-thrombotic syndrome, which is manifested by pain and swelling of the legs. During normal pregnancy, physiological hypercoagulability (increased blood clotting) develops as a defense mechanism against excessive blood loss during childbirth. Women who receive folic acid regularly develop less hypercoagulation.

It is especially important during pregnancy and in the period of preparation for it to know the status of folate cycle enzymes (MTHFR), to control the level of homocysteine, folate in order to adjust the diet in time and make a decision on the appointment of synthetic folic acid, which can help genetic test MyFeminity .

You can order the MyFeminity test with a 5% discount using the special promo code BL-STER

Sources of natural folates

A person can metabolize various forms of folic acid, but cannot synthesize the precursor (pteroglutamic acid) and, accordingly, must receive it from food or dietary supplements. In addition, the microflora of the large intestine synthesizes active forms of vitamin B9 from the precursors supplied with food.

Folic acid and natural folates, after intake with food, undergo a series of transformations and become biologically active. Plant-based folates are unstable and degrade easily when heated, animal-based folates are more heat-resistant, and synthetic folic acid is heat- and UV-resistant.

Foods high in folate: asparagus, soy, spinach, okra, broccoli, Brussels sprouts, Chinese sprouts, bell peppers, green beans, lentils, pinto beans, black beans, lima beans, green peas, peanuts and peanut butter, liver cod.

Other sources of folate:

• Chard, kale, lettuce, iceberg lettuce, watercress, parsley, basil, cilantro
• Green beans, white cabbage, carrots
• Oranges, grapefruits, mangoes, raspberries, strawberries, avocados, pomegranates
• Cereals (wheat, corn, buckwheat, rice, oats, barley), bran
• Whole rye flour, wheat flour of the 2nd grade
• Whole wheat bread, whole grain pasta
• Sunflower seeds, sesame, hazelnuts, walnuts

Because vegetable folates are rapidly destroyed by heat, minimal heat is recommended.

Too much folic acid

Unfortunately, it is impossible to take folic acid uncontrollably, synthetic folic acid can accumulate in the blood when taken in excess. At the same time, natural folates from plant foods are quickly metabolized and excreted from the body. An excess of folic acid derivatives in the blood is possible only when taking large doses (more than 1000 mg) of a synthetic drug.