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High homocysteine levels are associated with an increased risk of cardiovascular and cerebrovascular disease. Hyperhomocysteinemia can be caused by several mechanisms: (1) genetic defects in the enzymes involved in the metabolism of homocysteine, (2) nutritional deficiencies in vitamin cofactors, or (3) some chronic medical conditions and drugs. Smoking may increase homocysteine levels in the blood.
In the absence of known cardiovascular or cerebrovascular disease, it is controversial whether or not to treat patients with elevated homocysteine levels. There is no clear evidence for treating patients who do not have severe hyperhomocysteinemia in the absence of cardiovascular or thrombotic disease.[1] There are conflicting data on the efficacy of supplementation aimed at lowering homocysteine levels to prevent vascular events and death in patients with established vascular disease.[2-4] For patients who are treated, the treatment should target the underlying cause, if known.
In general, a diet rich in fruits, vegetables, and low-fat dairy products as well as low in saturated and total fat can help to decrease serum homocysteine. For patients with known cardiovascular disease, it is generally recommended to treat with folic acid (1 mg/day), vitamin B6 (10 mg/day), and vitamin B12 (0.4 mg/day). Folic acid can be increased up to 5 mg/day to reach a goal of lowering homocysteine levels below 15 mmol/L. In patients refractory to 5 mg/day of folic acid, 750 mg twice daily of trimethylglycine have been used, but there are only limited data demonstrating efficacy.[1] It is known that trimethylglycine enhances the methylation metabolism of homocysteine.
Although treating hyperhomocysteinemia can be very important, it should go without question that the more significant cardiovascular risk factors, such as diabetes, hypertension, hypercholesterolemia, and tobacco use, must also be addressed.
High homocysteine levels are associated with an increased risk of cardiovascular and cerebrovascular disease. Hyperhomocysteinemia can be caused by several mechanisms: (1) genetic defects in the enzymes involved in the metabolism of homocysteine, (2) nutritional deficiencies in vitamin cofactors, or (3) some chronic medical conditions and drugs. Smoking may increase homocysteine levels in the blood.
In the absence of known cardiovascular or cerebrovascular disease, it is controversial whether or not to treat patients with elevated homocysteine levels. There is no clear evidence for treating patients who do not have severe hyperhomocysteinemia in the absence of cardiovascular or thrombotic disease.[1] There are conflicting data on the efficacy of supplementation aimed at lowering homocysteine levels to prevent vascular events and death in patients with established vascular disease.[2-4] For patients who are treated, the treatment should target the underlying cause, if known.
In general, a diet rich in fruits, vegetables, and low-fat dairy products as well as low in saturated and total fat can help to decrease serum homocysteine. For patients with known cardiovascular disease, it is generally recommended to treat with folic acid (1 mg/day), vitamin B6 (10 mg/day), and vitamin B12 (0.4 mg/day). Folic acid can be increased up to 5 mg/day to reach a goal of lowering homocysteine levels below 15 mmol/L. In patients refractory to 5 mg/day of folic acid, 750 mg twice daily of trimethylglycine have been used, but there are only limited data demonstrating efficacy.[1] It is known that trimethylglycine enhances the methylation metabolism of homocysteine.
Although treating hyperhomocysteinemia can be very important, it should go without question that the more significant cardiovascular risk factors, such as diabetes, hypertension, hypercholesterolemia, and tobacco use, must also be addressed.
Hyperhomocysteinemia is a condition characterized by high levels of homocysteine in the blood. This can be caused by genetic factors or issues with the metabolism of homocysteine, and has been linked to an increased risk of cardiovascular diseases, blood clots, and other health problems. Treatment usually involves dietary changes, supplementation with vitamins like B6, B12, and folate, and in some cases, medications.
Folate is important in cell division and DNA synthesis, and is required to properly transcribe DNA, transform norepinephrine into adrenalin, as well as transform serotonin into melatonin. Folate also works with vitamins B6 and B12 to suppress the toxic amino acid homocysteine, an amino-acid byproduct that damages artery walls, promotes inflammatory conditions and platelet clotting as well as atherosclerotic plaque formation, which contributes to the hardening of blood vessels and can result in the development of cardiovascular disease and many other health problems. Decreasing homocysteine levels protects your heart and blood vessels. Folate, along with vitamins B6 and B12, convert homocysteine into cysteine or methionine, both of which are harmless. Folate might also help protect against cancers of the lung and cervix, and may help slow memory decline associated with aging. Folate works with vitamin B12 to help prevent cognitive impairment.
Folate can:
- Prevent birth defects: Folate supports the growth of the placenta and fetus, and it helps to prevent several types of birth defects, especially those of the brain and spine, such as malformation of the neural tube. As a fetus develops, the top part of this tube helps form the baby's brain, and the bottom part becomes the baby's spinal column. If the neural tube fails to close properly, the baby can be born with serious brain and spinal problems. Mothers with inadequate supplies of folate give birth to a greater number of infants with neural tube defects. Beginning in the early 1980′s, researchers began to successfully use folate supplementation to reduce the risk of nervous system problems in newborn infants. In addition, adequate folate intake prevents cleft lip and palate. Because defects can occur in an embryo before a woman realizes that she's pregnant, it's important for all women ages 15 to 45 to include folate in their diets.
- Support red blood cell production and help prevent anemia: Folate allows for the complete development of red blood cells, which help carry oxygen around your body. When folate is deficient, your red bloods cannot form properly, and continue to grow without dividing in a condition called macrocytic anemia.
- Help prevent cardiovascular disease and cancer: Folate helps maintain healthy circulation of your blood throughout your body by preventing build-up of a substance called homocysteine. A high serum homocysteine level (called hyperhomocysteinemia) is associated with increased risk of cardiovascular disease and cancer, and low intake of folate is a key risk factor for hyperhomocysteinemia. Increased intake of folate can lower your risk of cardiovascular disease and cancer by preventing build-up of homocysteine in your blood.
- Support healthy skin, mouth, gums, lungs, intestines, and other tissues: Cells with very short life spans (like skin cells, intestinal cells, and most cells that line your body's exposed surfaces or cavities) are highly dependent on folate for their creation. For this reason, folate deficiency has repeatedly been linked to problems in these types of tissue. In your mouth, these problems include gingivitis and periodontal disease. In your skin, the problems include seborrheic dermatitis and vitiligo (loss of skin pigment). Cancers of the esophagus and lung, uterus and cervix, and intestine (especially the colon) have been repeatedly linked to folate deficiency.
- Allow nerves to function properly: Deficiency of folate has been linked to a wide variety of nervous system problems, including general mental fatigue, dementia, depression, restless leg syndrome, nervous system problems in the hands and feet, irritability, forgetfulness, confusion, and insomnia. Folate helps synthesize your nervous system's message-carrying molecules, called neurotransmitters, and helps keep them in balance. High homocysteine levels caused by deficiency of folate can also lead to the deterioration of dopamine-producing brain cells and may therefore contribute to the development of Parkinson's disease.
- Help prevent osteoporosis-related bone fractures: Low levels of folate significantly increases your risk of osteporosis-related bone fractures due to the resulting increase in homocysteine levels. People with the highest levels of homocysteine also have a much higher risk of osteoporotic fracture. Conversely, folate reduces the risk of osteoporotic fractures by reducing high levels of homocysteine.
- Help prevent dementias, including Alzheimer's disease: Low blood levels of folate are also linked to dementias, including Alzheimer's disease. People whose blood levels of folate were lowest had more than triple the risk for mild cognitive impairment, and risk of dementia increased almost four fold. Homocysteine, a potentially harmful product of cellular metabolism that is converted into other useful compounds by folate, along with vitamin B6 and B12, was also linked to dementia and Alzheimer's disease. People whose homocysteine levels were elevated had a more than four-fold increased risk of dementia and an almost four-fold increased risk of Alzheimer's disease.
Homocysteine is an amino acid in the blood. Studies have shown that too much homocysteine in the blood (plasma) is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. High levels of homocysteine have been linked to cardiovascular disease. As a result, the American Heart Association (AHA) has recently named homocysteine as a risk factor for heart attack and stroke. Now, new research is suggesting that homocysteine plays a part in such diverse health concerns as osteoporosis, depression, Alzheimer’s disease and pregnancy. To understand how one molecule can do so much, we need to take a closer look at this compound. Homocysteine is an amino acid, although not one of the twenty "standard" amino acids that serve as the building blocks of protein in our bodies. Homocysteine is not found in our diet, and thus the answer to why it represents such a problem lies in examining how it is produced in our bodies. To understand homocysteine, one must first have an appreciation of its relationship to the vitamins B6, B12, and B8 (more commonly known as folic acid). When proteins are metabolized, they are broken down into individual amino acids, including the sulfur-containing amino acid methionine. Methionine is in turn broken down further in several steps to produce homocysteine, which, once formed, can be removed from the body in only two ways. One, it can be remade into methionine through a process called remethylation. This requires both folic acid and vitamin B12, where B12 functions as an essential "cofactor" in the reaction. Secondly, homocysteine can be made into the amino acid cysteine through a process called transulfuration, a process that requires two enzymes to work in concert with vitamin B6. Thus, if a person ingests lots of protein, and there is not enough folic acid, B6 and B12 available to help digest it, homocysteine levels can build up in the blood stream. As might be expected, the opposite is also true. Increased levels of these vitamins in the blood stream result in a reduction of homocysteine levels. Indeed, studies have shown that oral folic acid supplements are effective in bringing homocysteine levels down. In a seesaw effect, as folic acid levels rise in the blood stream, levels of homocysteine drop. n the meantime, cholesterol was getting all the press as the cause of cardiovascular disease. Warnings went out to avoid it in our diets to lower our risk of heart attacks and strokes. "Good" and "bad" cholesterol became household words and it became widely believed by the general public that if you could just lower that cholesterol, you wouldn’t need to worry about a heart attack. However, while high cholesterol clearly increases the risk of having a heart attack, it has always been the case that many heart attack victims actually have normal cholesterol levels. And thus there must be more to the story, and the search for answers has led back to those early observations by Dr. McCully. Recent research has confirmed his hunch that homocysteine was playing a part in heart disease, and lately much has been made in the popular press about homocysteine as the "new cholesterol," or the "cholesterol of the 90s." Homocysteine, perhaps working in tandem with cholesterol, may indeed be behind the development of arterial plaques, which deposit where the wall of an artery has been damaged. But although cholesterol is part of the sticky plaque material, it is has never been clear whether cholesterol itself is the culprit that breaks down the arterial wall in the first place. Now studies have shown that homocysteine damages the smooth vascular wall tissue, creating a scratch in the inside of the vessel where plaque can build up. Although more research needs to be done, it looks like homocysteine causes toxic superoxide radicals to form in the blood, which in turn kill cells in the blood vessel walls. Once damaged, the affected area swells and forms a "rough spot" where sticky cholesterol, (along with platelets and white blood cells that arrive to fix the damage) start to collect into a plaque. The problem is further exacerbated because homocysteine travels around the blood stream linked to low density lipoproteins (also known as LDLs, or "bad cholesterol"), the kind of cholesterol that builds up into plaques. And as if that were not enough, homocysteine can also thiolate (add sulfur groups) to LDLs, which causes them to be even more sticky and also attracts more white blood cells. All these reasons add up to point the finger at homocysteine as a potent new "bad guy" in the world of heart disease. This evidence, and studies linking high homocysteine to both heart attack and clogging of the arteries (atheroschlerosis), finally prompted the AHA to add homocysteine to the more well known risk factors for heart disease (such as smoking, high blood pressure, high cholesterol levels, obesity and lack of exercise). But the bad work of homocysteine does not stop with damaging the circulatory system. Besides being suspected as a causative agent of atheroschlerosis, there are some early clues that homocysteine plays a role in proper brain function. When researchers looked at how nutrition could affect depression, they found that low levels of folic acid increased the symptoms of depression and prevented anti-depressant medications from working well. Of course because of the see-saw effect, patients with low folic acid levels have high levels of homocysteine, and these high homocysteine levels may themselves contribute to the problem. Homocysteine appears to inappropriately stimulate some nerve cell receptors, which can hinder normal brain function. High homocysteine levels also lead to high levels of S-adenosylmethionine (SAM, which is needed to make neurotransmitter molecules) and S-adenosyl homocysteine (which inhibits the proper methylation of some brain chemicals). Thus, elevated homocysteine levels may adversely affect a whole range of brain processes, and cause or worsen psychological abnormalities. Of course because high homocysteine and low folic acid levels go hand in hand, it is hard to know which of these molecules is more important in combating depression. It will likely turn out to be a combination of both. High levels of homocysteine have now also been linked to diseases that cause dementia such as Alzheimer’s Disease. Deficiencies in vitamin B12 and folic acid have already been linked to neuropsychiatric disorders, although the biochemical reasons for these relationships remain to be worked out. Now, although the research is still in its early stages, it seems that certain thinking skills, such as making sense of visual input and understanding spatial relationships, are decreased by high homocysteine levels. Such links of folic acid, vitamins B6, B12 and homocysteine to cognitive function suggest that good nutrition may help prevent, or at least delay, the onset of diseases such as Alzheimer’s, good news in an age where more and more people are living longer, healthier lives. However, keeping homocysteine levels in check is not just important as we age. Homocysteine has been identified as playing an important part in healthy fetal development. High maternal homocysteine levels in the bloodstream increase the chance of miscarriage, and of serious pregnancy complications such as pre-eclampsia and placental abruption. Such conditions can result in premature birth of the baby, low birth weight and, sadly, even the death of the baby or mother. Clearly, preventing high homocysteine levels during pregnancy is important for the health of both mother and child. Luckily, because folic acid has gotten so much attention as a vital nutrient for preventing serious neural tube birth defects such as Spina Bifida, pregnant women and women planning to get pregnant are already routinely advised to take folic acid supplements, which has the added benefit of keeping homocysteine levels down as well. The results from these studies that link high homocysteine levels with poor pregnancy outcomes now make taking those folic acid supplements during pregnancy doubly important. As if all these studies pointing to the importance of homocysteine in human health are not enough, high homocysteine levels have even been proposed as causative agents for osteoporosis, a condition where bones become progressively weaker in postmenopausal women, and presbyopia, far sightedness due to aging. Connections to yet other health disorders are sure to follow. Yet despite the mounting evidence that high homocysteine levels correlate to increased risk of heart attack, stroke, birth defects, mental health problems, and perhaps other ailments, studies still need to be done to determine if lowering homocysteine levels in the general population, perhaps by supplementing the food supply, could increase our health as a nation. Because folic acid supplements do significantly lower homocysteine levels in the blood stream, such proposals to add folic acid to foods have been made. Proponents note that the addition of vitamin B6 to the food supply has resulted in a gradual drop in death from cardiovascular causes since the 1960s. However, such plans are controversial, for one because folic acid supplements can mask the symptoms of pernicious anemia, a vitamin B12deficiency that hampers the bone marrow’s ability to make blood, which can cause irreversible nerve damage. Thankfully, in the absence of metabolic defects that keep homocysteine levels abnormally high, all the risks associated with high homocysteine levels seem to be avoidable with good nutrition. Leafy green vegetables, orange juice and beans are good sources of folic acid. Vitamin B6 is found in starchy foods such as whole grains, potatoes, bananas, as well as turkey and tuna, and vitamin B12 is found in meat, seafood and dairy products. A well balanced diet can provide ample amounts of these important nutrients. Much work on this simple yet powerful molecule still needs to be done. While high homocysteine levels are found in tandem with many ailments, proving a real biochemical connection between homocysteine and disease is important before serious recommendations can be made about diet and vitamin supplementation. Scientists will need to unearth more clues as to the harmful effects of homocysteine, and then hopefully come up with practical ideas to apply this knowledge for the health of everyone.
Broccoli is a nutritious food. It's a good source of vitamin C, iron, fiber, potassium, vitamin A, calcium, zinc, magnesium, carotene, and B vitamins. It is important in the prevention of certain types of cancer, along with diabetes, heart disease, osteoporosis, and high blood pressure.
Broccoli can:
- Help prevent cancer. Hundreds of research studies on broccoli have focused on the connections between inflammation, oxidative stress, detoxification, and cancer. In fact, broccoli contains anti-inflammatory nutrients, antioxidant nutrients, detoxification-support nutrients, and anti-cancer nutrients. The unique combination of antioxidant, anti-inflammatory, and pro-detoxification components in broccoli make it a unique food in terms of cancer prevention. Connections between cancer development and oxidative stress, chronic inflammation, and inadequate detoxification are so well-documented in the research that any food improving all three of these metabolic problems would be highly likely to lower your risk of cancer. Broccoli is most likely to decrease your risk of prostate cancer, colon cancer, breast cancer, bladder cancer, and ovarian cancer, and may decrease your risk of other cancer types.
- Prevent inflammation. Two cups of broccoli have just 100 calories, and approximately 450 milligrams of omega-3 essential fatty acids (in the form of alpha-linolenic acid, or ALA), about the amount provided by one soft gel capsule of flax oil. You get important anti-inflammatory benefits from the omega-3 essential fatty acids in broccoli.
- Reduce the impact of allergens. Broccoli is a rich source of one particular phytochemical (a flavonol) called kaempferol. Especially inside of your digestive tract, kaempferol can reduce the impact of allergens by lowering your immune system's production of IgE-antibodies. By reducing the impact of allergens, the kaempferol in broccoli can help lower your risk of chronic inflammation.
- Prevent oxidative stress. Broccoli is a concentrated source of an important antioxidant nutrient, vitamin C, along with significant amounts of flavonoids kaempferol and quercitin, which allow vitamin C to recycle and provide longer-term support of oxygen metabolism in your body. Broccoli also contains the carotenoids lutein, zeaxanthin, and beta-carotene. All three of these carotenoids function as key antioxidants. In the case of lutein and beta-carotene, broccoli not only provides significant amounts of these antioxidants, but also significantly increases their blood levels when you eat at least three cups. Other antioxidants provided by broccoli in beneficial amounts include vitamin E and the mineralsmanganese and zinc. Considered as a group, the vitamins, minerals, flavonoids, and carotenoids contained in broccoli work to lower risk of oxidative stress in your body. An average of 1/2 cup of broccoli per day (only 22 calories' worth) is enough to provide measurable benefits. A 2-cup serving twice a week would also provide this level of benefit, with only 178 calories, or 1% of the total weekly calories. Three cups of broccoli per day can help optimize levels of antioxidants in the blood, especially beta-carotene and lutein, and optimal antioxidant levels can help lower the risk of oxidative stress in healthy cells, which also helps lower their risk of becoming cancerous.
- Fight chronic inflammation. The ability of these nutrients to support oxygen metabolism and avoid excess formation of overly reactive, oxygen-containing molecules makes them equally helpful in lowering risk of chronic inflammation and risk of cancer. The glucosinolates and omega-3 fats in broccoli also help fight cancer by reducing chronic inflammation. The anti-inflammatory substances in cruciferous vegetables may help prevent heart disease, especially the anti-inflammatory properties of sulforaphane, one of the isothiocyanates (ITCs) derived from the glucoraphanin in broccoli. In some individuals susceptible to high blood sugar, sulforaphane may be able to prevent (or even reverse) some of the damage to blood vessel linings that can be cause by chronic blood sugar problems, and may decrease risk of heart attacks and strokes.
- Eliminate toxins. Most toxins that pose a risk to your cells must be detoxified in your body by a multi-step process. Broccoli can affect each of these detoxification steps. Isothiocyanates (ITCs) made from the glucosinolates in broccoli affect the first and second steps in detoxification (called Phases I and II). By helping to promote as well as regulate detoxification activity in your cells, the ITCs made from broccoli can help prevent insufficient detoxification of dangerous substances that threaten your cells. The glucoraphanin in broccoli, which your body converts into sulforaphane, supports detoxification. Because skin cells can carry out the process of detoxification, sulforaphane may be especially important in helping to counteract sun damage.
- Support digestive health. Broccoli supports your digestive health with fiber and isothiocyanates (ITC). Only 250 calories worth of broccoli-12% of a 2,000-calorie diet-gives you about 25 grams of fiber, or 100% of the Daily Value (DV). Few nutrients support your digestive health as well as fiber. The speed that food travels through your digestive tract, the consistency of food as it moves through your intestines, and bacterial populations in your intestines are all supported and regulated by fiber. Alongside of broccoli's dietary fiber are its phytochemicals called glucosinolates. Many stomach problems are linked with overgrowth of bacteria called Helicobacter pylori, and also with excessive attachment of these bacteria to your inner stomach lining. Your body converts these into isothiocyanates (ITCs). ITCs-and particularly sulforaphane-help protect the health of your stomach lining by helping prevent bacterial overgrowth of Helicobacter pylori and helping prevent the bacteria from clinging to your stomach wall. Raw broccoli sprouts are particularly useful in this regard. The glucosinolates in broccoli may also alter gene expression in cells that provide your stomach with its inner lining.
- Lower cholesterol. Broccoli also supports your heart by lowering cholesterol. Your liver uses cholesterol to produce bile acids, which are specialized molecules that emulsify fat so that it can be digested and absorbed. Your body stores bile acids in fluid form in your gall bladder, and when you eat a fat-containing meal, they get released into your intestine where they help ready the fat to interact with enzymes and get absorbed into your body. When you eat broccoli, fiber in it bind with some of the bile acids in your intestine so that they stay inside your intestine and pass out of your body in a bowel movement, rather than getting absorbed along with the fat they have emulsified. When this happens, your liver needs to replace the lost bile acids by drawing upon your existing supply of cholesterol, and as a result, your cholesterol level drops. Broccoli provides you with this cholesterol-lowering benefit whether it is raw or cooked. However, the cholesterol-lowering ability of raw broccoli improves significantly when it is steamed.
- Support cardiovascular health. The B-complex vitamins in broccoli can also make a major contribution to your cardiovascular health. Homocysteine is a substance that raises your risk of atherosclerosis, stroke, and heart attack. Three B vitamins especially important for lowering your risk of hyperhomocysteinemia (excessive formation of homocysteine) are vitamin B6, vitamin B12, and folate. By making an important contribution to your vitamin B6 and folate intake, broccoli can help you lower your risk of excessive homocysteine formation and related cardiovascular problems.
- Support eye health. Two carotenoids found in significant concentrations in broccoli-lutein and zeaxanthin-play an especially important role in the health of your eyes. In fact, no tissue in your body is more concentrated with lutein than the area in the outer portion of your retina called the peripheral retina. Similarly, in the macula near the central portion of your retina, zeaxanthin is uniquely concentrated. Risk of problems involving the maculas of your eyes (such as macular degeneration) and problems involving the lenses of your eyes (such as cataracts) can be prevented by eating foods like broccoli that provide significant amounts of the lutein and zeaxanthin.
- Support vitamin D metabolism. Broccoli is an unusually good source of vitamin K and also of vitamin A (as beta-carotene). If you take large supplemental doses of vitamin D to offset deficiency, ample supplies of vitamin K and vitamin A can help keep your vitamin D metabolism in the proper balance.
- Support skin health. Hesperetin, found in broccoli, works together with vitamin C to maintain healthy collagen, which prevents sagging and wrinkling of your skin. Hesperetin is also used to treat venous insufficiency and hemorrhoids, may also have anti-inflammatory effects, may also treat vascular disorders, cancer, and some autoimmune diseases, might also be an anti-allergen, can improve capillary health and connective tissues, may help with bruising, varicose veins, and fragile capillaries, and may also help and get rid of hay fever and other similar allergies.
Broccoli is rich in vitamin A: its dark green color as indicates its high carotene content. Broccoli contains folate, calcium, and iron. One cup of cooked broccoli has as much vitamin C as an orange, and actually fulfills your daily requirement. Broccoli is low in calories, with only 44 calories for one cup chopped and cooked and 24 calories for one cup raw chopped. It also contains protein and fiber, along with vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B6 (pyridoxine), magnesium, potassium, and zinc. Broccoli, along with other cruciferous vegetables, may be important in preventing of some types of cancer. Because of its beta carotene, vitamin C, calcium, fiber, and phytochemicals, specifically indoles and aromatic isothiocynates, broccoli may boost enzymes that help to detoxify your body and prevent cancer, diabetes, heart disease, osteoporosis, and high blood pressure. Broccoli may also help lower blood cholesterol, because it contains a pectin fiber called calcium pectate that binds to bile acids. Broccoli's high level of the trace mineral, chromium, may be effective in preventing adult-onset diabetes in some people, because it enhances the ability of insulin to transport glucose from your bloodstream into your cells.
