Anti aging: Maximising methylation
Folic acid and vitamin B12 are the prime contributors to methyl groups and you obtain these essential nutrients from your diet. Green vegetables cater for your folic acid needs, while animal products such as meat, salmon, sardines and egg yolk supply your vitamin B12 stores. To enter the methylation cycle, folic acid has to be activated via a number of biochemical steps and these all require energy. To manufacture this energy we need nutrients that include the B vitamins, zinc, magnesium, iron, manganese, the amino acid cysteine and coenzyme Q10. In my clinical experience, these nutrients often aren’t present in sufficiency, which makes it more difficult to facilitate the activation of folic acid and to transfer methyl groups ultimately to SAMe.
Are you vitamin B deficient? If you look at your tongue in the mirror and it has a strawberry edge or you have small cracks or sores at the side of your mouth, it’s likely you are low in B vitamins. Wounds that take a long time to heal or a poor sense of taste suggest zinc deficiency, while cramps in the lower part of your legs or constant flickering of your eyelids indicate magnesium is not serving you. These insufficiencies should be addressed through diet and supplementation to ensure adequate methylation takes place in your body. You cannot underestimate the importance of methylation to anti aging.
To promote methylation reactions and the delivery of methyl groups you need enzymes. Genetic defects, or what are known as “single nucleotide polymorphisms”, compromise the way this happens. They can be overcome by taking supplementary folic acid in high amounts or by using an alternative biochemical pathway, which utilises a food source called choline, found in beans and egg yolk. The ingestion of choline causes a knock-on effect that allows for the methylation of SAMe.
To find out how this biochemistry is playing out in your cells, your health practitioner can order tests that assess your gene polymorphisms, your nutrient levels (including vitamin B12, folic acid, manganese and iron via blood tests) and your zinc and magnesium status (via a 24-hour urine profile).
Another crucial substance that needs to be measured is homocysteine, as this amino acid is an intermediate on the way to the methylation of s-adenosylmethionne. If you have genetic defects with regard to enzyme polymorphisms or inadequate supplies of vitamin B12, folic acid or the other B vitamins (especially B2, B3 and B6), homocysteine will be inadequately methylated and it will start to accumulate in your bloodstream. This increases your risk of heart disease, raised blood pressure and Alzheimer’s dementia.
Status tests need to be ordered pre-emptively to prevent the biochemical payload of methylation defects. Initially, the most obvious signs may be emotional and mental health problems including depression and learning and memory deficits with deterioration of cognitive function. However, other often-silent fallout also occurs, with devastating consequences, such as the development of cancer.
The current trend towards fortifying foods with folic acid may contribute to methylation problems. Professor David Smith, who heads the Oxford Project to Investigate Memory and Aging in the United Kingdom, points out that supplementing with folic acid might prevent neural tube defects but also brings with it a number of adverse biochemical consequences. Pregnant mothers with high folate levels and low B12 status give birth to babies who have a greater chance of being overweight.
Smith also warns that too much folic acid circulating in the bloodstream might interfere with the enzymes that drive folate metabolism in the methylation cycle, which would jeopardise the way genes are methylated. This has ramifications for not only the development of obesity but also the origins of cancer and dementia.
Anti aging: The cancer–folic acid link
The connection between cancer and nutrient status is complex. Deficiencies of folic acid, vitamin B6, zinc and selenium have all been linked to methylation defects and the development of cancer. In this context, replacing folic acid lowers the risk of bowel cancer. However, animal studies on colorectal cancer have shown that the timing and dose of folic acid are paramount. If folic acid supplementation is started before the establishment of cancer, the development of the cancer is stifled, but once cancer cells have set up shop, taking extra folic acid will enhance the growth and progression of cancer.
In his review of this literature, Professor Smith highlights research showing that in a large study of 24,500 postmenopausal women, those who reported taking a high dosage of supplementary folic acid (more than 400ug/day) had a 19 per cent higher risk of breast cancer, whereas those whose intake was in the highest quintile (>835ug/d) had a 32 per cent greater risk of developing this cancer.
Folate is required for cell growth and division as well as DNA repair. Low folate status is associated with impaired DNA repair and adverse DNA methylation, which can be corrected with supplementation of folic acid. Once cancer is established, supplementing with folic acid can have the opposite effect, though. It helps cancer cells to replicate and can lead to methylation of tumour suppressor genes, which switches them off.
This means you should supplement with folic acid only if you are deficient. In the future, your methylation profile may also be assessed to determine intervention strategies and the nutrients you need to impact on the way your genes are expressed in a positive way. Laboratories around the world are developing techniques to assess genome-wide methylation and, although these aren’t freely available yet, their commercial reality is imminent.
Anti aging, Dementia and Alzheimer’s disease
If folic acid status poses a conundrum when it comes to preventing cancer, its relationship with dementia is even more problematic. Research out of the United States has revealed that elderly people with low vitamin B12 status and normal folate levels have a 70 per cent increased risk of cognitive impairment, whereas those with high folate levels and low vitamin B12 have an even greater risk. An imbalance of B12 and folate, especially elevated levels of folate, may interfere with the metabolism of folate and the methylation cycle. The end result? A loss of DNA methylation, leading to reduced adult neurogenesis or brain cell production and age-related declines in learning and memory performance.
The amyloid precursor protein gene is thought to contribute to the inherited form of Alzheimer’s disease. Switching on this gene leads to the accumulation of amyloid beta protein, which is associated with the brain tangles that develop in Alzheimer’s disease. Hypomethylation of the amyloid precursor protein gene occurs with ageing and might be connected with your folic acid or vitamin B12 status.
Anti aging: Inflammation and methylation
Chronic infection and inflammation contribute to up to 25 per cent of cancers worldwide. As an instigator of cancer growth as well as other aging diseases such as atherosclerosis and dementia, inflammation needs to be countered before its insidiously pernicious effects take hold. Free radical stress, in turn, increases inflammation, a silent process that can creep up on you. By the time you notice that malignant lump, suffer a heart attack from blocked blood vessels or can’t think properly because your brain cells are tangled and dysfunctional, your chance to save your life and wellbeing might be lost. That’s good reason to act now before it’s too late to intervene.
You can check your inflammation status by means of a blood test that measures HS-CRP or other inflammatory markers, identified by more specialised laboratories, including interleukin-6, or IL-6, and tumour necrosis factor alpha. If your HS-CRP test is elevated, examine the underlying causes of inflammation. The most common cause is being overweight, which is often associated with insulin resistance or the inability of the hormone insulin to facilitate the entry of sugar or glucose into your cells. This leads to glucose travelling around your bloodstream and causing all sorts of harm via a mechanism known as glycation.
Infection with germs such as Helicobacter pylori and Chlamydia pneumoniae (connected with inflammation of your blood vessels, which leads to heart disease) can also kickstart inflammation. Similarly, other causes include food allergy/intolerance, stress, elevated homocysteine, free radical overload, heavy metal stress (from metals such as lead, mercury, cadmium and aluminium) and a lack of protective germs in your bowel. These inflammation issues can be uncovered by doing the appropriate tests under the supervision of a health practitioner who recognises and appreciates the importance of diagnosing and addressing markers of inflammation before the problem takes complete hold.
Anti aging & Glycation: binding up your body
The process of glycation occurs when a sugar molecule binds to a protein, lipid or nucleic acid. There, it forms a molecule of irregular shape that your body can’t get rid of or metabolise normally. This reaction results in the formation of complexes known as Schiff bases and Amadori adducts. For example, when the haemoglobin that carries oxygen around your bloodstream becomes glycated or glycosylated, an unhealthy substance called HbA1C I is formed (this is measured to assess blood sugar control in diabetics). The Amadori adducts are then acted on by free radicals to form AGEs (advanced glycation end-products). AGEs disrupt protein-like collagen, leading to the ageing of your skin, and they damage the structures in your eyes, which diminishes your visual function. Even more lethal is the effect AGEs have on your blood vessels, dramatically intensifying your chances of succumbing to a heart attack, stroke and dementia.
What actually raises your blood glucose levels? Inadequate insulin function (see box). AGEs interact with a receptor to form RAGEs (receptors of AGEs). As its name suggests, this triggers a flurry of adverse biochemical reactions, including inflammation and heightened free radical stress. These, in turn, ignite atherosclerosis and the ageing of your brain cells. RAGEs reduce insulin function even further, intensifying this biochemical disaster by making more glucose available for glycation.
To bring this melodrama and the effects of glycation full circle, once glycation intensifies inflammation and the accumulation of free radicals, these then affect methylation adversely to age you prematurely and increase your risk of developing cancer. In light of this, it’s important to find out whether your blood glucose and inflammatory status are working for or against you with respect to methylation, one of the most vital processes in your body. Enlist the assistance of a health practitioner who knows how to evaluate these states so you can take the necessary steps to preserve methylation, which expresses your DNA in a healthy and vital fashion.