Assessment of Methylation Status Part 4

Dr. Alex Jimenez Explains Methylation Status, Inflammation and Oxidative Stress

As previously mentioned in the past series of articles, doctors can use a variety of clinical assessments to evaluate the methylation status of their patients. Although no assessment method or technique can accurately determine a patient's methylation activity, current assessments can provide a better understanding of methylation-related genetic polymorphisms, nutrient status, methylation-related neurotransmitters and neurotransmitter metabolites, amino acids, hormones and metabolites, oxidative stress, and detoxification load. Each of these processes and substances can help doctors and patients understand their methylation status.

Understanding Methylation Status

Various assessment methods and techniques, including measures utilized to determine DNA methylation status, are usually exclusive to research studies and are not yet readily available to doctors. Until methylation status assessments become more widely available, further diagnosis is still required to understand diseases, especially since conflicting outcome measures have been found in research studies on the various methodologies. Although methods and techniques from research studies have rapidly started to evolve, patterns of DNA methylation status in humans across cells, tissues, age, populations, environmental factors like nutrition and lifestyle modifications, as well as disease, have only just started to become more widely recognized by researchers and doctors.

It is fundamental that we focus on a variety of these indicators and that we become aware of the restrictions of our interpretations and their misunderstood factors. Plasma homocysteine, by way of instance, can decrease as methylation activity increases, but, it can also decrease when oxidative stress levels increase, regardless if methylation activity increases. However, as we’ve previously mentioned, only several SNPs have known, quantifiable alterations in enzymatic function and their overall outcome measures on methylation remain unknown. Doctors must rely on a variety of clinical assessments to evaluate the methylation status of their patients. In the following articles, we will continue to discuss methylation status assessment options available to doctors for patients.

Understanding Inflammation

Inflammation increases the production of cytokine which can alter a patient's methylation status in a variety of ways. DNA methylation activity is also tremendously affected by inflammation-related signaling molecules. Cytokines, chemokines, free radicals, prostaglandins, growth factors, and matrix metalloproteinases, are produced during inflammation, altering epigenetic changes in DNA methylation activity. IL-1β, by way of instance, suppresses p53 expression, creating a more favorable environment for tumorigenesis. NFκB is a central transcription factor triggered by inflammation which also regulates the expression of more than 400 genes.

Moreover, it directly regulates NKκB-dependent histone demethylase which in turn regulates the fate and transdifferentiation of tumor cells. IL-6, another inflammatory signaling molecule, regulates the activity of DNMTs, microRNAs and histone methyltransferases which affect the epigenetics of p53 tumor suppressor genes by reducing expression. TNF-alpha increases in mitotically-preserved and region-specific DNA methylation activity in a way that seems to include impaired cellular differentiation and renewal. In vitro outcome measures suggest that inflammation may also promote the production of methyl radicals which trigger DNA methylation activity in normal, unmethylated tumor suppressor genes, causing gene silencing and carcinogenesis.

Inflammation can also cause a metabolic milieu that drains methylation resources, by way of instance, through the dysregulation of glucose homeostasis. Pro-inflammatory molecules can also alter insulin signaling in peripheral tissues, reducing inflammatory mediators that promote insulin signaling. Insulin dysfunction and hyperglycemia promote elevated levels of oxidative stress which triggers increased utilization of glutathione and depleted homocysteine, methionine and SAMe. Furthermore, DNA methylation patterns affecting metabolism and inflammation were identified in adipose tissue from subjects with type 2 diabetes.

Understanding Oxidative Stress

Oxidative stress is closely associated with inflammation. States of elevated, or chronic, oxidative stress can negatively alter DNA methylation through two mechanisms. First, oxidative stress increases the demand for glutathione synthesis, which pulls homocysteine towards transulfuration pathways, at the expense of methylation pathways and SAMe formation. Second, oxidative stress and increased hydroxyl radical formation can damage DNA and change the ability of DNA methyltransferase enzymes to appropriately methylate DNA. This is one of the most common causes of global DNA hypomethylation and specific areas of hypermethylation.

DNA guanine nucleotides are main regions of DNA damage caused by oxidative stress, which is why they are frequently utilized as a biomarker for DNA-level oxidative stress, or 8OHdG. Generally, guanine functions as a hydrogen bond acceptor to promote the creation of methyl binding protein, or MBP, DNA complexes. However, oxidation of guanine considerably decreases MBP binding when combined to the 5- methylcytosine nucleotide. Additionally, 5-methylcytosine, or 5-mC, may also experience oxidation or hydroxylation, forming 5-hydroxymethylcytosine, or 5-hmC, through oxidative stress. This can tremendously affect interactions with DNA-proteins that can prevent their binding affinity to MBPs, leading to potentially heritable epigenetic alterations.

The methods and techniques commonly utilized to determine DNA methylation can't distinguish between 5-mC and 5-hmC, which may prove to be an essential distinction, especially in the brain, where most DNA hydroxymethylation can be found. There is outcome measures which demonstrate that acute psychological stress can increase DNA hydroxymethylation in the hippocampal glucocorticoid receptor gene. This epigenetic alteration can lead to the development of neuropsychiatric and neurodegenerative disorders. Aging is also associated with increases in 5-hmC in the brain which may be prevented by caloric restriction and antioxidant upregulation.

A variety of research studies have found that DNA methylation can be affected by inflammation, most commonly caused due to oxidative stress. Increasing outcome measures have also demonstrated that methylation activity may become affected in response to both nutritional and environmental influences. Alterations in DNA methylation caused by inflammation and oxidative stress can lead to problems in gene expression, increasing the potential risk of disease. Understanding the effects of inflammation due to oxidative stress is fundamental when investigating epigenetic mechanisms. DNA methylation assessments based on inflammation and oxidative stress can help patients regulate their overall health and wellness.

Dr. Alex Jimenez D.C., C.C.S.T. Insight

Smoothies and Juices for Methylation Support

While many healthcare professionals can recommend nutritional guidelines and lifestyle modifications to improve methylation support, there are several options you can try yourself at home. As described above, methylation support supplementation should be determined by a healthcare professional. Smoothies and juices are a fast and easy way to include all the necessary nutrients you need for methylation support without any side-effects. The smoothies and juices below are part of the Methylation Diet Food Plan.

Sea Green Smoothie

Servings: 1

Cook time: 5-10 minutes

? 1/2 cup cantaloupe, cubed

? 1/2 banana

? 1 handful of kale or spinach

? 1 handful of Swiss chard

? 1/4 avocado

? 2 teaspoons spirulina powder

? 1 cup water

? 3 or more ice cubes

Blend all ingredients in a high-speed blender until completely smooth and enjoy!

Berry Bliss Smoothie

Servings: 1

Cook time: 5-10 minutes

? 1/2 cup blueberries (fresh or frozen, preferably wild)

? 1 medium carrot, roughly chopped

? 1 tablespoon ground flaxseed or chia seed

? 1 tablespoons almonds

? Water (to desired consistency)

? Ice cubes (optional, may omit if using frozen blueberries)

Blend all ingredients in a high-speed blender until smooth and creamy. Best served immediately!

Sweet and Spicy Juice

Servings: 1

Cook time: 5-10 minutes

? 1 cup honeydew melons

? 3 cups spinach, rinsed

? 3 cups Swiss chard, rinsed

? 1 bunch cilantro (leaves and stems), rinsed

? 1-inch knob of ginger, rinsed, peeled and chopped

? 2-3 knobs whole turmeric root (optional), rinsed, peeled and chopped

Juice all ingredients in a high-quality juicer. Best served immediately!

Ginger Greens Juice

Servings: 1

Cook time: 5-10 minutes

? 1 cup pineapple cubes

? 1 apple, sliced

? 1-inch knob of ginger, rinsed, peeled and chopped

? 3 cups kale, rinsed and roughly chopped or ripped

? 5 cups Swiss chard, rinsed and roughly chopped or ripped

Juice all ingredients in a high-quality juicer. Best served immediately!

Zesty Beet Juice

Servings: 1

Cook time: 5-10 minutes

? 1 grapefruit, peeled and sliced

? 1 apple, washed and sliced

? 1 whole beet, and leaves if you have them, washed and sliced

? 1-inch knob of ginger, rinsed, peeled and chopped

Juice all ingredients in a high-quality juicer. Best served immediately!

Protein Power Smoothie

Serving: 1

Cook time: 5 minutes

? 1 scoop protein powder

? 1 tablespoon ground flaxseed

? 1/2 banana

? 1 kiwi, peeled

? 1/2 teaspoon cinnamon

? Pinch of cardamom

? Non-dairy milk or water, enough to achieve desired consistency

Blend all ingredients in a high-powered blender until completely smooth. Best served immediately!

ProLon? Fasting Mimicking Diet

Balanced methylation support can be achieved through proper nutrition. The ProLon? fasting mimicking diet offers a 5-day meal program which has been individually packed and labeled to serve the foods you need for the FMD in precise quantities and combinations. The meal program is made up of ready-to-eat or easy-to-prepare, plant-based foods, including bars, soups, snacks, supplements, a drink concentrate, and teas. The products are scientifically formulated and great tasting. Before starting the ProLon? fasting mimicking diet, 5-day meal program, please make sure to talk to a healthcare professional to find out if the FMD is right for you. The ProLon? fasting mimicking diet can help promote methylation support, among a variety of other healthy benefits.

Many doctors and functional medicine practitioners may recommend higher doses of methyl donors in several patients, however, further research studies are needed to determine the proper amount of methylation supplementation. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions.

Curated by Dr. Alex Jimenez