In our ongoing series of articles on the emerging and exciting field of Nutrigenomics we continue to explore and demystify topics such as epigenetics, polymorphism, gene expression and methylation. We also look at the practical application for nutritional genomics with individual genetic profiles.
Genes from Birth
We are born with the DNA, the genes, that we ‘inherit’ from our parents. The most recent research now demonstrates that the diet of the mother at a preconception stage and onward can significantly influence the expression of genes we are born with
(link to this story below). In pregnancy and breastfeeding the diet of the mother is critical for the baby’s health, as are the choices our parents make in what they feed us from infancy through to teenage years.
In adulthood the factors that can impact on our health, specifically in relation to the field of nutrigenomics, comprise our diet, fitness, the stresses of our life and how we handle them, ‘abuse’ factors such as alcohol, drugs and tobacco, and ‘environmental’ issues such as pollution.
The fields of epigenetics and nutrigenomics look at aspects of our genetic profile to establish what ought to nutritionally work best for us in terms of diet and maintaining good health; you might say this is ‘optimal’ nutritional advice for individuals.
For those with existing chronic illnesses, or ongoing medical conditions, this approach seeks to establish whether aspects of the individuals genetic profile are playing a significant role in the illness in terms of nutrition. Typically this means that a lack of a certain nutrient (or nutrients), or a failure in their assimilation due to the individuals genetics, is a major factor in attempting to resolve or mitigate the illness.
Even for those in apparent ‘excellent health’ a genetic profile can indicate ‘susceptibilities’ toward certain health conditions, particularly in later life. So if for instance a profile shows errors of methylation that could predispose a to Alzheimer’s then it may be advisable for that person to take higher and ongoing levels of methyl donor nutrients, than someone without that susceptibility.
When you read about ‘epigenetics’ and ‘nutrigenomics’ – the closely related fields that deal with these genetic health and nutritional issues you may frequently encounter the terms ‘methylation’, ‘polymorphisms’ and ‘SNP’s’ (pronounced ‘snips’). Below is a brief definition:
Epigenetics – the study of heritable changes
Epigenetics is the study of genetic changes over generations that are not caused by a change in DNA sequence (e.g. methylation, histone modification). The changes are brought about through the way genes are expressed which has happened to permit the best survival possible of the parents and grandparents in their environment.
For instance the Pima Indians faced times of hardship and their genes evolved to be thrifty and to make the best out of poor food sources. i.e. they learnt to synthesise simple sugar from fibre and to store their food far better than we should do today. This gene was fine is time of hardship but subsequent generations encountered lush times and their ability to hold on to food stores meant that they easily got fat in times of plenty. This gene is still carried by people today and you can appreciate the problem.
Polymorphism – a change in one letter of DNA sequence
If a small genetic change occurs in an individual, i.e. a change in one letter of DNA sequence, it is called a “mutation” (Latin for change). A genetic variation is called a polymorphism when more than 1% of the population is known to have that same genetic change. Polymorphisms can be very common and some could be carried by up to 50% of the population.
The most common type of polymorphism is called a Single Nucleotide Polymorphism (SNP -which is pronounced ‘snip’). This means that just one of the letters, the chemical bases of the DNA, either an A, T, C or G, is different. So for example an ‘A’ may have been replaced with a ‘T.’ As these letters code for different amino acids, changing one to another may result in a different amino acid being slotted into a bodily structure as it is being built. This will then change the structure and function of what has been created. For example one of the most discussed SNPs ‘MTHFR’, affects how the body metabolises folic acid.
Nutrigenomics is the study of the effects of foods on ‘gene expression’. We provide an overview on gene expression below. To put it simplistically some of the genes we are born with can become active or inactive during our lives. And diet/nutrition plays the pivotal role in being able to influence turning these genes on and off during our life.
By identifying the unique genetic makeup of an individual, and which of their genes can be influenced by nutrition, the ultimate application of nutrigenomics is to personalise the nutritional advice for the individual to maximise their good health and minimise potential health risks or predispositions.
So nutrigenomics focuses on understanding the interaction at molecular level between nutrients and the genome and identifying the causality/relationship between specific nutrients and diets on health. It can be termed ‘personalised nutrition based on genotype’. Nutrigenomics focuses on the role specific foods have in activating genes that affect susceptibility to certain illnesses such as Alzheimer’s and cancers.
The relevance of Gene Expression & ‘Signalling’
Gene expression is the process by which the genetic code of a gene is used to direct protein synthesis and produce the structures of the cell. Genes encode proteins and the proteins ‘dictate’ the cell function. Consequently the thousands of genes expressed in a particular cell determine what that cell can do.
With each step in the processing of information from DNA to RNA to protein provides the cell with a potential control point for self-regulating its functions by adjusting the amount and type of proteins it manufactures.
Or in another analogy DNA codes for RNA, that codes for Proteins. RNA is a ‘copy’ (e.g. like a pdf document) and cannot be changed, but its expression can be changed via the protein attachments. DNA regulates gene expression which in turn regulates cell growth, cell differentiation, cell replication and cell death.
We are born with the genes we inherit from our parents. As part of foetal development the chemical process of ‘methylation’ plays a key role. Methylation is a key step in the formation of our enzymes and proteins and this process is called ‘genetic transcription’.
As a result of methylation we are born with genes that are either a) permanently switched off b) permanently switched on; or c) have the ability to be switched on or off and this change is most likely to occur through the factors of nutrition, environmental and stress.
Thus dietary components can act directly or indirectly to alter certain gene expression. The earlier in life we are exposed to a specific diet the more susceptible we appear to be to its long term health-effects due to lifelong alterations in some gene expression. This recent evidence indicates that some gene expression of offspring is altered irreversibly at time of conception and dictated by the diet of parents.
Methylation is one of the body’s most important and most common chemical processes, occurring a huge number of times a second in every cell and organ of the body. Methylation is a process that is vital for health. It is the addition of a methyl group, or ‘CH3’, to many chemical compounds.
Methylation plays many essential roles and is one of the body’s most important ‘Phase II’ detoxification reactions. This is where methyl groups (CH3) are donated to molecules that would otherwise be considerably more harmful; particularly to proteins and DNA.
Methylation is not only vital for detoxification, it plays a key role in many essential health functions throughout our lives including neurotransmitter synthesis and utilization, protein synthesis from our genes, hormonal regulation and the reduction of inflammation.
More recently genetic analysis indicates that as many as 40% of people have SNPs relating to methylation. This means that not only is there the potential for gene expression to be altered but for phase II detoxification pathways in the liver to be impacted too. Both these factors are among the most crucial determinants for an increased risk of developing one or more chronic diseases.
People can be ‘under-methylators’ or ‘over-methylators’ and both experience impaired methylation reactions which predispose to disease states. Importantly the risks can be modified by ensuring the availability of sufficient methyl donor nutrients and their co factors.
Some health professionals dislike the terms ‘under or ‘over’ methylators. However it is undisputed that many people have insufficient methyl groups for health. This may be due to lack of intake from diet, impaired methyl reactions (e.g. due to SNPs), age or a combination of factors. Supplementation can provide a key role in providing suitable methyl donors with Betaine TMG, Methylcobalamin vitamin B12, and Methylfolate as Folic Acid being particularly relevant examples.
‘Nutrigenetics’ is also used to describe a discipline for investigating the relationship with an individual in terms of their genes and nutritional (etc.) influences.
Nutrigenetics is about the close cause-effect relationship between specific nutrients and nutritional regimes and how they act on an individual’s genetic make-up and on the development of specific metabolic disorders. If this sounds the same as nutrigenomics then the purist and specialist may argue that nutrigenetics focuses on metabolic disorders and genetic susceptibility whilst nutrigenomics focuses on activating gene expression for individual health benefits.
Nutrigenetics has been described as ‘seeking to identify why one food is good for one person and bad for another’ and ‘identifying how our genetic makeup makes us respond or not to dietary intervention’.
Finally a specialist field relating to ‘preventative genomics’ is an emerging branch of medicine that identifies polymorphisms (mutations) in individuals in order to predict the likelihood of that individual developing a disease or imbalance when in a certain environment and to use that information to modify their environment and diet to prevent disease from developing. Again other health professionals would argue that this topic is covered in the application of nutrigenomics and epigenetics.
Put simply one can see that the use of an epigenetic profile will give us individually an understanding on our susceptibility to certain illnesses and tell us whether this can be modified through sensible and normal means such as a good diet, exercise and food supplements – or whether more is needed.
It does not need to be a more complex exercise than that, except in people who are currently chronically ill (as opposed to acutely). So if for instance a profile shows a susceptibility to Alzheimer’s then it would be advisable for that person to take higher levels of B12 and methyl donor nutrients ongoing, than someone without that genetic susceptibility whose diet was also supportive.
One might also consider that the field of nutrigenomics can be used to help support the exploration of both epigenetic changes of gene expression and polymorphisms. Some might call this nutrigenetics for the former. Perhaps the main thing is for us to understand the difference between epigenetic change and polymorphisms – and that nutrition as part of an individualised programme would be implicated in both to modify the impact on health.
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A Footnote on Folic Acid:
For supplementation of folic acid we only recommend methylfolate. Methylfolate (5MTHF) is the most stable, safe and bioeffective form of folate. Read our article on folic acid and methylfolate: Cytoplan Blog: Methylfolate