Watching a white minibus taxi on its way to Zimbabwe over a long weekend suddenly created the image that an overloaded taxi is not a patch on what gets loaded into our bloodstreams!
The bloodstream starts with plasma loaded with red and white blood cells as well as platelets made in the bone marrow; then collecting other substances such as nutrients from the digestion of food and drinks; oxygen via the lungs from the air that we breathe; cellular waste products; and a variety of hormones excreted from a vast array of glands, including the liver and kidneys. All these substances in the bloodstream are somehow involved in a myriad of biochemical processes taking place in the body.
It follows that the contents of the bloodstream would give a good indication of what is really happening in the body. A battery of blood tests connects the dots like the pieces of a puzzle that together forms an overall picture of your health.
If you can afford only one test as a dipstick to get a good indication of your health, that test would be for homocysteine.
Where does homocysteine come from?
The essential macronutrients that the body needs from your diet are carbohydrates, fat, and protein. Carbohydrates and proteins are water-soluble macromolecules and together with lipids (fat) they represent the major sources of calories in the diet. Each of the three macronutrients supplies specific building blocks for molecules that are needed for the physiologic functioning of the body.
Carbohydrates are the major source of the glucose that is used by the cells in the body as an energy source.
Fat is an important dietary component, as it not only makes food palatable, but it has many important functions in the body, for example being stored for extra energy (mostly under the skin, where it also acts as insulator to help maintain body temperature), and for making cell membranes and the protective sheaths of nerve fibers.
Proteins gets broken down during digestion into small molecules, called amino acids, which can be absorbed into the bloodstream to be transported through the body. Amino acids are the building blocks of proteins in the body.
Individual amino acids are linked together in a special way into sequences to form unique proteins, each with its unique function in the body. There are an estimated 50 000 different proteins in the body.
Twenty different amino acids are used to make the proteins that cells in the body need. Ten of these are called “essential” amino acids, which the body doesn’t make and the only way to obtain them is from food. One of these essential amino acids is methionine, from which homocysteine is made through a process called methylation. Examples of food rich in methionine are beef, lamb, turkey, pork, fish, shellfish, nuts, cheese, soy, eggs, dairy, and beans.
Homocysteine and methylation:
The body can be compared to a chemical factory, as the body contains millions of chemical molecules, for example glucose, fats, hormones, neurotransmitters, and amino acids, to name a few. The process by which the body keeps all the chemicals in balance is called methylation. During the methylation process, methyl groups – consisting of one carbon and three hydrogen atoms – are added to or removed from other molecules.
Methylation is the process by which the body transforms one biochemical into another, by either making the substances that it needs or breaking down those substances that it doesn’t need. This process happens over a billion times a second and Patric Holford compares it with one big dance, “with biochemicals passing methyl groups from one partner to another”.
Methylation is also the process by which homocysteine is made. When a methyl group is taken away from the essential amino acid methionine inside the cells, the methionine becomes homocysteine.
Significance of homocysteine:
When methionine is converted into homocysteine, a normal functioning body changes it quickly in one of two possible ways:
- By adding a different methyl group to the homocysteine, it gets converted into an important chemical called S-adenosyl methionine (SAMe), which acts as a natural anti-depressant and is also anti-arthritic, as well as playing a role in protecting the liver.
- Adding a different methyl group converts homocysteine into an important chemical called glutathione, which acts as an excellent anti-ageing antioxidant and detoxifying agent.
Which is why homocysteine is such a good dipstick to see what is happening in the body. The best and most sensitive test for effective and healthy methylation is the homocysteine level. High homocysteine levels indicate methyl deficiency, meaning that methylation is not working properly, leading to chemical imbalances in the body, such as a deficiency in SAMe, glutathione, and other vital biochemicals.
The homocysteine conversion process not only depends on the adding of different methyl groups. Other co-factors also play a role, such as vitamins and nutrients that help the homocysteine enzymes (acting as chemical catalysts) to function properly during the biochemical conversion process. A lack of these helpers means the chemical catalysts cannot function properly, resulting in homocysteine accumulating in the body. For the conversion to SAMe the enzymes need folate, vitamin B12, vitamin B2, zinc, and TMG as helpers, while the conversion to glutathione needs vitamin B6, vitamin B2, and zinc as helpers.
The relatively unknown TMG (trimethylglycine) is an amino acid derivative that occurs in plants. It serves as a “methyl giver” as it provides one of its methyl groups to assist with methylation. This biochemical action reduces homocysteine into L-methionine and/or increase SAMe levels.
Effects of high homocysteine levels on your health:
During the normal processing of food, drinks, and oxygen, the body ends up with damaged forms of oxygen, called oxidants, also known as free radicals. This is a normal process, however compounding factors, for example smoking, eating browned or burnt food, breathing in exhaust fumes, and chronic inflammation results in more oxidants in the body. These oxidants have damaging effects on the skin, the lungs, the brain, the digestive tract, the arteries and even on DNA. As a result, oxidation plays a role in many diseases and high levels of homocysteine have been found to directly increase oxidation.
Healthy levels of homocysteine, around five to 15 micromoles per liter (mmol/L), means that nearly all the homocysteine has been converted to other proteins and only small amounts remain in the bloodstream. Normally, very little homocysteine stays in your blood.
However, the levels of homocysteine circulating in the bloodstream may increase due to defects in the enzymes involved in the methylation of methionine, eating lots of food rich in methionine, and deficiencies of the B vitamins (6,12, and 9), folate, zinc, and TMG. Some medications such as lipid (fat) lowering drugs and anti-Parkinsonian drugs are known to elevate homocysteine levels.
Levels of homocysteine fall in four categories, namely –
- Healthy levels: 5 – 15 micromoles/liter
- Moderately high: 16 – 30 micromoles/liter
- Intermediately high: 31 – 100 micromoles/liter
- Severely high: over 100 micromoles/liter.
Heath conditions associated with high levels of homocysteine:
High levels of homocysteine, called hyperhomocysteinemia, shows in several age-related health conditions such as cardiovascular disease, stroke, osteoporosis, Parkinson’s disease, and Alzheimer’s disease. It is also associated with other health conditions such as cancer, hypothyroidism, aortic aneurysm, end stage renal disease, and even with depression, migraine, and retinal vein occlusion. Increased homocysteine does not necessarily mean that someone will develop these conditions, it means that prolonged high levels may raise the risk.
Cardiovascular disease: High levels of homocysteine can damage the lining of arteries (endothelial dysfunction) and may also cause the blood to clot more easily than it should, which can increase the risk of blockages in blood vessels. Homocysteine is associated with damage to cells and tissues in the lining of arteries through eliciting the release of too many cytokines and cyclins, mediators of inflammation and cell division. Too many cyclones can trigger high levels of inflammation and may cause blood vessels to become overly porous. Cytokines are molecules that serve as messengers between cells and are crucial for the healthy functioning of the immune system. Cyclins are responsible for the progression of the different phases of the cell cycle and plays a role in gene expression.
Apart from endothelial dysfunction, high homocysteine is also associated with impaired bioavailability of nitric oxide – a molecule whose most important function is relaxing the inner muscles of the blood vessels, causing them to widen and increase circulation, a process called vasodilation.
Increased homocysteine may also make the blood clot more easily, which can increase the risk of blockages in the blood vessels. Blood clots can also travel in the bloodstream and get stuck in the brain (causing a stroke), the heart (causing a heart attack), or the lungs (causing a pulmonary embolism).
Cognitive decline: Elevated levels of homocysteine is associated with cognitive decline, damage to the white matter in the brain (white matter contains nerve fibers called axons, which are each surrounded by a sheath called myelin, which gives white matter its colour), brain atrophy (a loss of nerve cells, called neurons, and connections between neurons), dementia, and neurofibrillary tangles.
The brain of an Alzheimer’s patient displays tangles and plaques that affects the transfer of impulses between neurons. The neurofibrillary tangles are bundles of filaments composed primarily of tau protein, a normal protein that transports nutrients into brain cells and move waste products out of brain cells. Homocysteine has been linked to abnormal tau, resulting in pieces of the tau protein to tangle and clump together. In this event the nutrients and toxic waste products can no longer move freely within brain cells and these cells may eventually die.
Animal studies have indicated that high homocysteine increases amyloid plaque formation. The fatty membrane that surrounds brain cells contain a protein molecule called beta-amyloid, which can cause plaque build-up outside the cells of the brain when it clumps together. Alzheimer’s disease results from loss of the brain’s neurons and synapses and tangles and plaques are the main contributors to Alzheimer’s disease.
In patients with Parkinson’s disease, an increase in homocysteine levels in blood levels and cerebrospinal fluid has been linked to cognitive decline and depression.
Stroke: Aging populations with hypertension have shown an association between high homocysteine and incidences of stroke. During a stroke, blood supply to the brain is interrupted, which may result in the death of neurons and loss of function in specific brain regions.
Osteoporosis: Increased homocysteine can affect bone density and remodeling in such a way that the bone matrix density (bone tissue forming most of the mass of the bone) is altered and osteoclast activity is stimulated, resulting in bones becoming less rigid, which increases the risk of fractures. Osteoclasts are the primary cell type responsible for bone absorption. Bone remodeling involves bone formation by osteoblasts and bone resorption by osteoclasts, a process called bone turnover. Interestingly, in terms of bone turnover, about 0,5 g of calcium passes back and forth daily between bone and the bloodstream, as bone serves as the short-term calcium-buffering system that prevents large swings in calcium levels in the bloodstream.
End stage renal disease: Homocysteine is strongly associated with end stage renal disease, as the deterioration in renal function is linked to high levels of homocysteine in the bloodstream. As renal function declines, ever increasing levels of homocysteine are found in the bloodstream. Dialysis may lower high homocysteine levels temporary, but it lasts only for a short time.
Insulin resistance and diabetes: Studies have indicated that raised maternal homocysteine levels during pregnancy may predict small infant size at birth, which is regarded as a risk factor for type 2 diabetes. Other studies correlated offspring obesity and insulin resistance at six years of age with increased maternal homocysteine levels and deficiencies in vitamin B12 and folate during pregnancy.
In adults, an association between elevated levels of homocysteine and insulin resistance and diabetes is well documented in studies in this regard. Insulin resistance is characterized by a decline in the capacity of cells to respond to normal levels of insulin, which forces the body to produce more and more insulin to prevent high blood sugar levels. Insulin resistance usually precedes diabetes, which is a chronic inflammatory disease characterized by increased levels of blood glucose and insulin. Increased homocysteine is a known factor in disrupting insulin signaling, which results in reduced glucose uptake.
Abdominal aortic aneurism: Studies have reported an association between increased homocysteine and abdominal aortic aneurism, which is a condition in which there is an enlarged area in the lower part of the aorta. The aorta is the largest blood vessel in the body and runs from the heart through the center of the chest and abdomen.
Hyperthyroidism: Increased levels of homocysteine has been found in hyperthyroidism (an overactivity of the thyroid gland), which is associated with an increased risk of cardiovascular disease.
Cancer: Studies have shown increased levels of homocysteine in cancer patients as a risk factor for cancer and a potential marker for tumors. Increased homocysteine may be caused by rapidly dividing tumor cells.
Inflammatory bowel disease: High levels of homocysteine have been implicated in affecting the intestinal vasculature, leading to inflammatory bowel disease, which is a condition that is characterized by chronic inflammation of the gastrointestinal tract.
Conclusions:
Using a homocysteine test as a dipstick can accurately indicate where you are on the scale of health and the level of risk you have for a wide range of serious health conditions.
Remember, homocysteine plays such a significant role in the biochemistry in the body, if you can afford only one blood test, homocysteine is the one!
References:
Homocysteine. Published 7 May 2021. Cleveland Clinic. (www.clevelandclinic.org)
High homocysteine level (hyperhomocysteinemia). Information updated 18 September 2018. Healthline. (www.healthline.com)
High homocysteine level: how it affects your blood vessels. Information updated 6 March 2022. Familydoctor.org. Medical advice from the American Academy of Family Physicians. (www.familydoctor.org)
High homocysteine levels: what to know. Information updated 6 March 2022. MedicalNewsToday. (www.medicalnewstoday.com)
Medical definition of homocysteine. Information reviewed 29 March 2021. MedicineNet. (www.medicinenet.com)
The metabolism and significance of homocysteine in nutrition and health. Published 22 December 2017. Nutrition & Metabolism. (Journal). National Centre for Biotechnology Information. US National Library for Medicine. National Institutes of Health. USA. (www.ncbi.nlm.nih.gov)
Medical Physiology. A systems approach. (Physiology Handbook). By Hershell Raff, Michael Levitzky, et al. Published 2011. McGraw Hill Medical. P 786.
How to lower your homocysteine level. Published 18 November 2021. Patrick Holford. (www.patrickholford.com)
Homocysteine. Published online. ScienceDirect. (www.sciencedirect.com)
The metabolism and significance of homocysteine in nutrition and health. Published 22 December 2017. Nutrition & Metabolism. Biomed Central Ltd. (www.nutritionandmetabolism.biomedcentral.com)
The South African fat and protein guide. Published 2006. Book by prof Nola Dippenaar and Liesbet Delport. A GIFSA publication. P. 153. (www.gifoundation.com)
The H factor. Book by Patrick Holford and Dr James Braly. Published 2003 by Piatkus Books Limited, London. P. 281.
HEALTH INSIGHT
June 2022