Genetic Testing in Integrative and Functional Medicine – Part 3
Genetic Testing and Metabolic Health
Metabolic syndrome and metabolic health have been studied extensively in the areas of integrative and functional medicine due to metabolic syndrome being a major risk factor for the development of diabetes mellitus 1 and cardiovascular disease. Genetic and environmental factors interrelate in a complex fashion to bring about this condition. A cluster of metabolic abnormalities, including hypertension, dyslipidemia, abdominal obesity, insulin resistance, and impaired glucose tolerance make up metabolic syndrome.
All of the components of metabolic syndrome are highly heritable. Studies have shown links between metabolic syndrome and genes such as PPARg, adiponectin, CD36, and beta receptors.
There has been a considerable investigation into the heritability of metabolic syndrome. One study involved over 2,200 individuals in over 500 family groups. It was the first to identify major genes influencing metabolic syndrome.
Chromosome 3q27 was significantly linked to six factors involved in metabolic syndrome: weight, leptin, insulin, waist circumference, hip circumference, and insulin/glucose ratio. Chromosome 17p12 was strongly linked to plasma leptin levels.
Another study evaluated over 200 SNPs in 110 genes for their effects on coronary artery disease, highly implicated in metabolic syndrome. SNPs in eight of these genes showed association with metabolic syndrome: LDLR, GBE1, IL1R1, TGFB1, IL6, COL5A2, SELE and LIPC.
These genes are described below:
- LDLR: Low Density Lipoprotein Receptor gene. It is strongly involved in the homeostasis of cholesterol. Hypercholesterolemia in families has been linked to mutations of this gene.
- GBE1: Glycogen Branching Enzyme gene. It is involved in coding the glycogen branching enzyme which aids in glycogen synthesis. Branching of these chains allows a great number of glycosyl units to be stored in a molecule of glycogen.
- IL1R1: Interleukin 1 Receptor, Type 1. Interleukin 1 is made up of two proteins, IL1-alpha and IL1-beta, and is a mediator of inflammation.
- TGFB1: Transforming Growth Factor, Beta 1. This gene encodes the peptide involved in many functions in cells. Apoptosis may result due to dysregulation of the activation of this gene.
- IL6: Interleukin 6 gene. It is a cytokine that regulates the immune response by activating a cell surface signaling assembly. Its production by neoplastic cells has been implicated in the growth of a number of cancers.
- COL5A2: Collagen, Type V, Alpha 2. Mutations in the gene may bring on weakened connective tissue throughout the body.
- SELE: Selectin E gene. May be involved in the pathogenesis of atherosclerosis.
Some of the more common inherited metabolic conditions include:
- Lysosomal storage disorders. These can result in the buildup of toxic substances inside lysosomes in the cells.
- Glycogen storage conditions. Sugar storage problems can lead to weakness, low blood sugar, and muscle pain.
- Mitochondrial disorders: Can lead to muscle damage.
- Peroxisomal disorders: Can lead to a buildup of toxic products of metabolism.
- Metal metabolism disorders: Special proteins control levels of trace metals in the blood. A malfunction in these proteins caused by genetic metabolism disorders can lead to toxic levels of metals in the body.
Symptoms of genetic metabolism disorders include:
- Low energy levels
- Decreased appetite
- Abdominal pain
- Weight loss
From this list of symptoms, it’s easy to see the relationship of metabolic syndrome and adrenal fatigue. Practitioners of integrative and functional medicine will be faced with patients who present with adrenal fatigue and these similar symptoms. This makes it important for them to understand at least the basics behind Adrenal Fatigue Syndrome (AFS).
Adrenal Fatigue Syndrome and Integrative and Functional Medicine
Feelings of fatigue and lethargy are presented more and more frequently in health care professionals’ offices. Combined with concentration difficulties, sleep problems, inability to lose weight, feeling your brain is in a fog, fatigue, and lethargy may point to AFS as the basic issue.
AFS is a constellation of many nonspecific symptoms that can become debilitating. The onset of the symptoms is slow and can be missed by traditionally trained professionals.
The symptoms of AFS result from the body’s normal response to stress from any source. The hypothalamic-pituitary-adrenal (HPA) axis is set into motion, releasing hormones and other chemicals that are designed to deal with stress. At the end of the axis are the adrenal glands that secrete cortisol, the stress fighting hormone. The purpose of this hormone is to limit the effects of stress on the body.
In normal circumstances, once the stress ceases, the cortisol levels decline and the adrenals get a chance to recover. However, in our stress-filled culture, the stresses continue. This puts the demand on the adrenals at an extreme level. At some point, the adrenals are no longer able to secrete cortisol, which results in damage to the body from the effects of stress.
Levels of inflammation and an increased immune response results. Inflammation has been implicated in many chronic illness conditions. It is at this point that the body begins breaking down from the accumulation of symptoms such as fatigue, brain fog, insulin resistance, and increasing inflammation.
NeuroEndoMetabolic (NEM) Response
The traditional medical viewpoint of addressing individual symptoms and/or organs when working to alleviate illness conditions is simply too mechanistic. A more comprehensive viewpoint is needed in order to effectively deal with symptoms of AFS. The NEM model is such a viewpoint.
The model says it is important to consider organ systems operating in an interrelationship in which whatever affects one organ system affects others as well. In this regard, it is in line with the integrative and functional medicine viewpoint.
The NEM model is a functional approach that looks at interactions between the individual’s environment and the gastrointestinal, endocrine, and metabolic organ systems, among others. This allows a healthcare practitioner to find the root causes, triggers, immediate causes, and genetic factors involved in a person’s illness condition.
This is a much more comprehensive approach to alleviating people’s symptoms and illness conditions.
Increasing and unrelenting stress is a part of our culture that is detrimental to the health of every individual. The metabolic component of the NEM model added to the neuroendocrine aspect helps professionals to see how localized organ-specific responses and systemic responses are necessary for successfully dealing with stress.
The metabolic component of our stress response is very subtle in the early stages. But the derangements of our metabolism worsen as time goes on and stress doesn’t stop. By the time the stress response reaches stage 3 or 4, these derangements can become debilitating. At the severe stage, they can lead to hypersensitivity to supplements and to paradoxical reactions.
Very significant and debilitating symptoms begin arising. Often, these lead the person to be bed-ridden due to their severity.
AFS and Genetics
A question integrative and functional medicine experts and those who suffer from AFS all want to know is: Can you inherit AFS?
Before answering that question, you need to understand even if you have a gene or several genes that are involved in a health condition like AFS, it doesn’t mean you will automatically get that condition. Before genes can do anything, either positive or negative, to your health, they have to get the signal to “switch on.”
One good thing about that signal is you have quite a bit of control over it. Scientists and researchers have discovered environment, choices you can make, exert significant control over whether genes are turned on or off. This is called gene expression.
Can you choose to switch specific genes on or off? That’s beyond us at this point. What you can do is make good lifestyle choices, good exercise choices, good diet choices and either activate or de-activate genes in this way. Genetic testing as seen in integrative and functional medicine practices is a way to determine your choices in many areas. Which diet works best for you and what exercises will best benefit you can be answered through this kind of testing.
Answering the specific question posed above, ‘Can you inherit AFS?’, is a complicated process.
Two genes with significant involvement in this answer are MTHFR and COMT. Both are involved with methylfolate. People with mutations in MTHFR don’t have enough methylfolate leading to less adrenaline because of interference in the methylation process. Methylation aids in the production of adrenaline and other hormones.
The other gene, COMT, is involved in the production of hormones and chemicals in the body. Low levels of methylfolate with this gene leads to lower levels of epinephrine and higher levels of norepinephrine.
The lack of methylfolate with both of these genes, especially MTHFR, leads to feelings of fatigue.
When your body is stricken by stress, both your adrenals and MTHFR are affected. This leads to the fatigue felt by those of you who suffer from AFS. The enzyme that produces dopamine and serotonin is also dependent on methylation to work right. Low levels of methylfolate can lead to low levels of both of these neurochemicals which can then lead to low energy and fatigue.
What Can You Do To Improve Energy Levels?
There are some things you can do to aid in increasing energy and improving the work of the two genes mentioned, MTHFR and COMT.
Balance your blood sugar levels by eating three or four small meals per day. These meals should include good grains like quinoa or rice, good carbs, and vegetables. You can add protein from fish or free-range chicken.
Supplements can help support your adrenal glands and the methylation process also. Vitamin B1, B2, and B6 will help. There are usually no side effects from vitamin B1, but if you should begin feeling any itching, notice any rashes, or have trouble breathing, contact your integrative and functional medicine healthcare professional immediately.
Side effects from B2 are also rare. Very yellow urine will be seen, but this is not serious. If you do have any rashes, breathing trouble, or itching, contact your physician at once.
Taken in large doses for a long time, B6 can cause side effects. Headache, nausea, and drowsiness are enough to contact your healthcare professional at once.
Some people try taking methylfolate (5-MTHF), but this is a labor-intensive effort and could bring on some serious side effects if your body is not ready for it. If your body gets overwhelmed by the 5-MTHF, you can feel headaches, irritability, anxiety, and heart palpitations. Get medical help right away for these side effects.
Despite advance testing, it is important to remember that tests are simply data points of alert. A clinical decision should be made after a detailed consideration of the history and state of the body. A shotgun approach to treating abnormal laboratory values is a common clinical mistake and can lead to negative clinical outcomes.
The mapping of the human genome has provided an opportunity for researchers and clinicians alike to consider the roles genes play in health and wellness. Discovering the presence and effects of single nucleotide polymorphisms (SNPs) has increased not only our knowledge of how genes affect health, but also has given us tools to use in preventing and remediating many chronic illness conditions.
Integrative and functional medicine practitioners have been among the professionals to use this information in a practical sense. Whether AFS can be inherited is yet to be seen. Clinically, we do see a strong correlation from one generation to the next.
Genetic testing to examine the working of MTHFR and COMT may be of some help. Diet and supplements can also increase your chances of these two genes working correctly and alleviating some of the symptoms of AFS.
Because integrative and functional medicine testing is still in the very early phase of development, it is important to take all data points with the right perspective and refrain from treating abnormal laboratory numbers while the root cause of the problem can be masked.
© Copyright 2018 Michael Lam, M.D. All Rights Reserved.