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Epigenetic’s

Back Clinic Epigenetics Functional Medicine Team. The study of heritable changes in gene expression (active versus inactive genes) does not involve changes to the DNA sequence, a change in phenotype without a change in genotype, which affects how cells read genes. An epigenetic change is a regular, natural occurrence that can also be influenced by several factors: age, environment, lifestyle, and disease state. Epigenetic modifications can commonly manifest as how cells terminally differentiate into skin cells, liver cells, brain cells, etc. And epigenetic change can have more damaging effects that can result in diseases.

New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases. Epigenetic marks are more stable during adulthood. However, they are still thought to be dynamic and modifiable by lifestyle choices and environmental influence. It is becoming apparent that epigenetic effects do not just occur in the womb but over the full course of human life. Another discovery is that epigenetic changes can be reversed. Numerous examples of epigenetics show how different lifestyle choices and environmental exposures can alter marks on DNA and play a role in determining health outcomes.


Good Foods to Help Promote Longevity

Good Foods to Help Promote Longevity

The foods we eat can have the potential to be beneficial or harmful to our health. Poor nutrition can cause a variety of health issues, including obesity, cardiovascular disease, and type 2 diabetes. Meanwhile, proper nutrition can make you feel energized, reduce your risk of health issues, as well as help maintain and regulate a healthy weight. If you want to promote longevity, you have to fuel your body with good foods. In the following article, we will list several good foods that can ultimately help promote longevity by also helping to improve overall health and wellness.

 

Cruciferous Vegetables

 

Cruciferous vegetables have the unique ability to change our hormones, trigger the body�s natural detoxification system, and even reduce the growth of cancerous cells. These must be chewed thoroughly or eaten shredded, chopped, juiced, or blended in order to release their beneficial properties. Sulforaphane, found in cruciferous vegetables, has also been found to help protect the blood vessel wall from inflammation that can cause heart disease. Cruciferous vegetables, such as kale, cabbage, Brussels sprouts, cauliflower, and broccoli are several of the most nutrient-dense foods in the world.

 

Salad Greens

 

Raw leafy greens have less than 100 calories per pound, which makes them the perfect food for weight loss. Eating more salad greens has also been associated with the reduced risk of heart attack, stroke, diabetes, and several types of cancers. Raw leafy greens are also rich in the essential B-vitamin folate, plus lutein and zeaxanthin, carotenoids that can help protect the eyes. Fat-soluble phytochemicals, such as carotenoids, found in salad greens like lettuce, spinach, kale, collard greens, and mustard greens also have antioxidant and anti-inflammatory effects in the body.

 

Nuts

 

Nuts are a low-glycemic food and a great source of healthy fats, plant protein, fiber, antioxidants, phytosterols, and minerals, which also helps to reduce the glycemic load of an entire meal, making them an essential part of an anti-diabetes diet. Regardless of their caloric density, eating nuts can help promote weight loss. Nuts can also reduce cholesterol and help reduce the risk of heart disease.

 

Seeds

 

Seeds, much like nuts, also provide healthy fats, antioxidants, and minerals, however, these have more protein and are rich in trace minerals. Chia, flax, and hemp seeds are rich in omega-3 fats. Chia, flax, and sesame seeds are also rich lignans or breast cancer-fighting phytoestrogens. Moreover, sesame seeds are rich in calcium and vitamin E, and pumpkin seeds are rich in zinc.

 

Berries

 

Berries are antioxidant-rich fruits that can help promote heart health. Research studies where participants ate strawberries or blueberries daily for several weeks reported improvements in blood pressure, total and LDL cholesterol, and even signs of oxidative stress. Berries also have anti-cancer properties and have been shown to help prevent cognitive decline associated with aging.

 

Pomegranate

 

The most well-known phytochemical in pomegranates, punicalagin, is responsible for more than half of the fruit’s antioxidant activity. Pomegranate phytochemicals have anti-cancer, cardioprotective, and brain-healthy benefits. In one research study, older adults who drank pomegranate juice daily for 28 days performed better on a memory test compared to those who drank a placebo beverage.

 

Beans

 

Eating beans and other legumes can help balance blood sugar, reduce your appetite, and protect against colon cancer. Beans are an anti-diabetes food that can help promote weight loss because they are digested slowly, which slows down the increase of blood sugar after a meal and helps prevent food cravings by promoting satiety. Eating beans and other legumes twice a week has been found to decrease the risk of colon cancer. Eating beans and other legumes, such as red beans, black beans, chickpeas, lentils, and split peas, also provides significant protection against other cancers.

 

Mushrooms

 

Eating mushrooms regularly is associated with a reduced risk of breast cancer. White and Portobello mushrooms are especially beneficial against breast cancer because they have aromatase inhibitors or compounds that inhibit the production of estrogen. Mushrooms have shown to have anti-inflammatory effects as well as provide enhanced immune cell activity, prevention of DNA damage, slowed cancer cell growth, and angiogenesis inhibition. Mushrooms should always be cooked as raw mushrooms have a potentially carcinogenic chemical known as agaritine that is significantly reduced by cooking.

 

Onions and Garlic

 

Onions and garlic provide cardiovascular and immune system benefits as well as provide anti-diabetic and anti-cancer effects. These have also been associated with a lower risk of gastric and prostate cancers. Onions and garlic are known for their organosulfur compounds which help to prevent the development of cancers by detoxifying carcinogens, decreasing cancer cell growth, and blocking angiogenesis. Onions and garlic also have high concentrations of health-promoting flavonoid antioxidants, which have anti-inflammatory effects that may help provide cancer prevention.

 

Tomatoes

 

Tomatoes are rich in a variety of nutrients, such as lycopene, vitamin C and E, beta-carotene, and flavonol antioxidants. Lycopene can help protect against prostate cancer, UV skin damage, and? cardiovascular disease. Lycopene is better absorbed when tomatoes are cooked. One cup of tomato sauce has about 10 times the amount of lycopene as a cup of raw, chopped tomatoes. Also keep in mind that carotenoids, like lycopene, are best absorbed when accompanied by healthy fats, so enjoy your tomatoes in a salad with nuts or a nut-based dressing for extra nutritional benefits.

 

 

The foods we eat can have the potential to be beneficial or harmful to our health. Poor nutrition can cause a variety of health issues, including obesity, cardiovascular disease, and type 2 diabetes. Meanwhile, proper nutrition can make you feel energized, reduce your risk of health issues, as well as help maintain and regulate a healthy weight. If you want to promote longevity, you have to fuel your body with good foods. Good foods can also help reduce inflammation associated with a variety of health issues, including joint pain and arthritis. Healthcare professionals, such as chiropractors, can offer diet and lifestyle advice to help promote health and wellness. In the following article, we will list several good foods that can ultimately help promote longevity. – Dr. Alex Jimenez D.C., C.C.S.T. Insight

 


 

Image of zesty beet juice.

 

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.

 


 

Image of carrots.

 

Just one carrot gives you all of your daily vitamin A intake

 

Yes, eating just one boiled 80g (2�oz) carrot gives you enough beta carotene for your body to produce 1,480 micrograms (mcg) of vitamin A (necessary for skin cell renewal). That’s more than the recommended daily intake of vitamin A in the United States, which is about 900mcg. It’s best to eat carrots cooked, as this softens the cell walls allowing more beta carotene to be absorbed. Adding healthier foods into your diet is a great way to improve your overall health.

 


 

The scope of our information is limited to chiropractic, musculoskeletal, physical medicines, wellness, and sensitive health issues and/or functional medicine articles, topics, and discussions. We use functional health & wellness protocols to treat and support care for injuries or disorders of the musculoskeletal system. Our posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate and support directly or indirectly our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require an additional explanation as to how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900. The provider(s) Licensed in Texas*& New Mexico*�

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • Joel Fuhrman, MD. �10 Best Foods You Can Eat to Live Longer and Stay Healthy.� Verywell Health, 6 June 2020, www.verywellhealth.com/best-foods-for-longevity-4005852.
  • Dowden, Angela. �Coffee Is a Fruit and Other Unbelievably True Food Facts.� MSN Lifestyle, 4 June 2020, www.msn.com/en-us/foodanddrink/did-you-know/coffee-is-a-fruit-and-other-unbelievably-true-food-facts/ss-BB152Q5q?li=BBnb7Kz&ocid=mailsignout#image=24.
Can You Change Your Epigenetic Clock?

Can You Change Your Epigenetic Clock?

Aging is a natural part of life and it can’t be stopped. Or at least, that’s what we used to think. Researchers at Intervene Immune, Stanford, the University of British Columbia, and UCLA believe that our epigenetic clock can be changed, suggesting that there may still be ways for humans to live longer. In the following article, we will discuss the findings associated with epigenetics and aging.

 

What is the Epigenetic Clock?

 

The epigenetic clock is a measurement of biological age that can be used to estimate the chronological age of humans or other organisms by testing several patterns of DNA methylation. Although the age estimated by the epigenetic clock frequently correlates with chronological age, it is not fully understood if DNA methylation profiles in the epigenetic clock are directly associated with aging.

 

For many years, researchers have observed age-related changes in gene expression and DNA methylation. However, the idea of using an “epigenetic clock” to be able to estimate chronological age by testing several patterns of DNA methylation was first proposed by Steve Horvath where it gained popularity after his 2013 research study was published in the journal Genome Biology.

 

Epigenetic clocks are used in forensic studies to determine the age of an unknown person through blood or other biological samples at the scene of a crime and in diagnostic screens to determine increased risks for diseases associated with aging, including a variety of cancers. Epigenetic clocks can also highlight whether several behaviors or treatments can affect epigenetic age.

 

Does Epigenetic Age Correlate with Chronological Age?

 

The main reason that epigenetic clocks and DNA methylation are used to estimate the chronological age of humans or other organisms is that they correlate very well with the chronological age in the subjects tested. The first research study on the epigenetic clock that Steve Horvath published in 2013 included 353 individual CpG sites identified from previous research studies.

 

Of these sites, 193 become more methylated with age and 160 become less methylated, which leads to the DNA methylation age estimate that is used to determine the epigenetic clock. Throughout all outcome measures, including all ages of subjects, Horvath observed a 0.96 correlation between the epigenetic age he calculated and the true chronological age, with an error rate of 3.6 years.

 

Current epigenetic clocks are also being evaluated to help further improve age prediction as well as the diagnostic and/or prognostic abilities of these tests. Further evaluations using NGS approaches ultimately have the potential to improve epigenetic clocks, making them more comprehensive by extending the evaluation of DNA methylation sites to all CpG sites in the genome.

 

Can We Change Our Epigenetic Clocks?

 

Research studies have demonstrated that cancer can change the epigenetic clock. These observations suggest that the epigenetic clock can change under certain conditions. Therefore, it is possible that the epigenetic clock can be manipulated through changes in behavior or treatment strategies to slow it down or potentially reverse it, allowing humans to live longer and healthier lives.

 

 

Researchers believe that our epigenetic clock can be changed. In the following article, we discussed the findings associated with epigenetics and aging. The epigenetic clock is a measurement of biological age that can be used to estimate the chronological age of humans or other organisms by testing several patterns of DNA methylation. The main reason that epigenetic clocks and DNA methylation are used to estimate the chronological age of humans or other organisms is that they correlate very well with the chronological age in the subjects tested. Current epigenetic clocks are also being evaluated to help further improve age prediction as well as the diagnostic and/or prognostic abilities of these tests. Research studies have demonstrated that cancer can change the epigenetic clock. Therefore, it is possible that the epigenetic clock can be manipulated through changes in behavior or treatment strategies to slow it down or potentially reverse it, allowing humans to live longer and healthier lives. By changing our epigenetic clocks, healthcare professionals may also be able to regulate age-related health issues, such as inflammation and joint pain. These could potentially be helpful for chiropractic care, an alternative treatment option that uses spinal adjustments to carefully restore the alignment of the spine.�- Dr. Alex Jimenez D.C., C.C.S.T. Insight

 


 

Image of zesty beet juice.

 

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.

 


 

Image of carrots.

 

Just one carrot gives you all of your daily vitamin A intake

 

Yes, eating just one boiled 80g (2�oz) carrot gives you enough beta carotene for your body to produce 1,480 micrograms (mcg) of vitamin A (necessary for skin cell renewal). That’s more than the recommended daily intake of vitamin A in the United States, which is about 900mcg. It’s best to eat carrots cooked, as this softens the cell walls allowing more beta carotene to be absorbed. Adding healthier foods into your diet is a great way to improve your overall health.

 


 

The scope of our information is limited to chiropractic, musculoskeletal, physical medicines, wellness, and sensitive health issues and/or functional medicine articles, topics, and discussions. We use functional health & wellness protocols to treat and support care for injuries or disorders of the musculoskeletal system. Our posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate and support directly or indirectly our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require an additional explanation as to how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900. The provider(s) Licensed in Texas*& New Mexico*�

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • Active Motif Staff. �Can You Really Reverse Your Epigenetic Age?� Active Motif, 1 Oct. 2019, www.activemotif.com/blog-reversing-epigenetic-age#:~:text=Epigenetic%20clocks%20are%20a%20measure,certain%20patterns%20of%20DNA%20methylation.
  • Pal, Sangita, and Jessica K Tyler. �Epigenetics and Aging.� Science Advances, American Association for the Advancement of Science, 29 July 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4966880/.
  • Matloff, Ellen. �Mirror, Mirror, On The Wall: The Epigenetics Of Aging.� Forbes, Forbes Magazine, 25 Jan. 2020, www.forbes.com/sites/ellenmatloff/2020/01/24/mirror-mirror-on-the-wall-the-epigenetics-of-aging/#75af95734033.
  • Dowden, Angela. �Coffee Is a Fruit and Other Unbelievably True Food Facts.� MSN Lifestyle, 4 June 2020, www.msn.com/en-us/foodanddrink/did-you-know/coffee-is-a-fruit-and-other-unbelievably-true-food-facts/ss-BB152Q5q?li=BBnb7Kz&ocid=mailsignout#image=24.
The Importance of Folate and Folic Acid

The Importance of Folate and Folic Acid

Folate is a B vitamin naturally found in a variety of foods. The body can’t produce folate, that’s why it’s important to get it from folate-rich foods. Folate is naturally found in various plant and animal foods, including citrus fruits, avocado, spinach, kale, broccoli, eggs, and beef liver. Folate is also added to foods, such as bread, flours, and cereals, in the form of folic acid or the synthetic, water-soluble version of folate. Folate and folic acid have different effects on the body.

 

Our body utilizes folate for a variety of essential functions, including cell division, development of red blood cells, conversion of homocysteine to methionine, an amino acid used for protein synthesis, production of SAMe, and DNA methylation. Folic acid is also important for various metabolic processes. Folate deficiency has ultimately been associated with a variety of health issues, such as the increased risk of heart disease, birth defects, megaloblastic anemia, and cancer.

 

Daily Intake of Folate and Folic Acid

 

Our body stores between 10 to 30 mg of folate, most of which is stored in your liver while the remaining amount is stored in your blood and tissues. Normal blood folate levels range from 5 to 15 ng/mL. The main form of folate in the bloodstream is known as 5-methyltetrahydrofolate. Daily intake of this essential nutrient is different for people of different ages. The recommended daily allowance of folate for infants, children, teens, adults, and pregnant women are as follows:

 

  • 0 to 6 months: 65 mcg
  • 7 to 12 months: 80 mcg
  • 1 to 3 years: 150 mcg
  • 4 to 8 years: 200 mcg
  • 9 to 13 years: 300 mcg
  • over 14 years: 400 mcg
  • during pregnancy: 600 mcg
  • during lactation: 500 mcg

 

Folic acid supplements play an important role in making sure that people who are in greater need of folate are getting enough of their daily intake. Increasing the daily intake of folate-rich foods is also important because these foods generally offer plenty of other nutrients that all act together to support overall health. Recommended folate daily intake increases during pregnancy and breastfeeding to promote rapid growth and help prevent neural tube defects in the fetus.

 

Folic acid is available in dietary supplements and fortified foods, including bread, flours, cereals, and several types of grains. It is also added to B-complex vitamins. Folate is also naturally found in a variety of foods, including:

 

  • oranges
  • orange juice
  • grapefruit
  • bananas
  • cantaloupe
  • papaya
  • canned tomato juice
  • avocado
  • boiled spinach
  • mustard greens
  • lettuce
  • asparagus
  • Brussels sprouts
  • broccoli
  • green peas
  • black-eyed peas
  • dry-roasted peanuts
  • kidney beans
  • eggs
  • Dungeness crab
  • beef liver

 

Uses of Folate and Folic Acid

 

Both folate and folic acid are frequently utilized for a variety of reasons. Although folate and folic acid supplements are generally used to treat similar health issues, they do offer different effects in the body and, therefore, it may affect our overall health in different ways. Moreover, getting the proper daily intake of folate and folic acid can improve overall health. The following are several of the most common uses of folate and folic acid supplements, including:

 

  • folate deficiency
  • inflammation
  • diabetes
  • brain health
  • heart disease
  • kidney disease
  • mental health issues
  • fertility problems
  • birth defects and pregnancy complications

 

For information regarding the importance of folate and folic acid, please review the following article:

The Importance of Folic Acid

 


 

 

Folate is a B vitamin that is naturally found in many different types of food. Because we can’t produce folate, it’s important to get it from foods that are high in folate. Various folate-rich foods include citrus fruits, avocado, spinach, kale, broccoli, eggs, and beef liver. Folate is also added to foods like bread, flours, and cereals, in the form of folic acid, the synthetic version of this essential nutrient. Folate and folic acid have different effects on the body. Our body uses folate for many important functions, including cell division, development of red blood cells, conversion of homocysteine to methionine, an amino acid used for protein synthesis, production of SAMe, and DNA methylation. Folic acid is also essential for many metabolic processes. Folate deficiency has ultimately been associated with a variety of health issues, such as heart disease, birth defects, megaloblastic anemia, and even cancer. Daily intake of this essential nutrient is different for people of different ages. Furthermore, folate is also naturally found in a variety of foods, such as bananas, avocado, boiled spinach, and eggs. Both folate and folic acid supplements have a variety of uses and they can help improve various health issues, including inflammation, diabetes, heart disease, birth defects, and pregnancy complications. Adding healthy foods to a smoothie is a fast and easy way to get your daily intake of folate. – Dr. Alex Jimenez D.C., C.C.S.T. Insight

 


 

Image of ginger greens juice.

 

Ginger Greens Juice

Servings: 1
Cook time: 5-10 minutes

� 1 cup pineapple cubes
� 1 apples, 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.

 


 

Image of soft-boiled and hard-boiled eggs.

 

Eating cholesterol-rich foods doesn�t increase your cholesterol

 

According to research studies, eating foods with HDL cholesterol or “good” cholesterol doesn’t increase your overall blood cholesterol levels. When you eat healthy cholesterol-rich foods, such as prawns and eggs, your blood cholesterol levels decrease, so your blood cholesterol levels stay balanced, or they’re only raised minimally. It’s actually saturated fats that you have to look out for when it comes to high blood cholesterol levels. Simply choose healthier food options.

 


 

The scope of our information is limited to chiropractic, musculoskeletal, physical medicines, wellness, and sensitive health issues and/or functional medicine articles, topics, and discussions. We use functional health & wellness protocols to treat and support care for injuries or disorders of the musculoskeletal system. Our posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate and support directly or indirectly our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require an additional explanation as to how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900. The provider(s) Licensed in Texas*& New Mexico*�

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • Kubala, Jillian. �Folic Acid: Everything You Need to Know.� Healthline, Healthline Media, 18 May 2020, www.healthline.com/nutrition/folic-acid#What-is-folic-acid?
  • Ware, Megan. �Folate: Health Benefits and Recommended Intake.� Medical News Today, MediLexicon International, 26 June 2018, www.medicalnewstoday.com/articles/287677#recommended-intake.
  • Felman, Adam. �Folic Acid: Importance, Deficiencies, and Side Effects.� Medical News Today, MediLexicon International, 11 Mar. 2020, www.medicalnewstoday.com/articles/219853#natural-sources.
  • Berg, M J. �The Importance of Folic Acid.� The Journal of Gender-Specific Medicine: JGSM: the Official Journal of the Partnership for Women’s Health at Columbia, U.S. National Library of Medicine, June 1999, pubmed.ncbi.nlm.nih.gov/11252849/.
  • Dowden, Angela. �Coffee Is a Fruit and Other Unbelievably True Food Facts.� MSN Lifestyle, 4 June 2020, www.msn.com/en-us/foodanddrink/did-you-know/coffee-is-a-fruit-and-other-unbelievably-true-food-facts/ss-BB152Q5q?li=BBnb7Kz&ocid=mailsignout#image=23.

 

MTHFR Gene Mutation and Health

MTHFR Gene Mutation and Health

The MTHFR or methylenetetrahydrofolate reductase gene is well-known due to a genetic mutation that may cause high homocysteine levels and low folate levels in the bloodstream, among other essential nutrients. Healthcare professionals believe that a variety of health issues, such as inflammation, may be associated with an MTHFR gene mutation. In the following article, we will discuss the MTHFR gene mutation and how it can ultimately affect your overall health.

 

What is an MTHFR Gene Mutation?

 

People can have single or multiple mutations, as well as neither, on the MTHFR gene. The different mutations are often referred to as “variants”. A variant occurs when the DNA of a specific part of a gene is different or varies from person to person. People that have a heterozygous or single variant of the MTHFR gene mutation have a decreased risk of developing health issues like inflammation and chronic pain, among other diseases. Moreover, healthcare professionals also believe that people that have homozygous or multiple variants of the MTHFR gene mutation may ultimately have an increased risk of disease. There are two MTHFR gene mutation variants. These specific variants include:

 

  • C677T. Approximately 30 to 40 percent of people in the United States have a mutation at gene position C677T. About 25 percent of Hispanics and about 10 to 15 percent of Caucasians are homozygous for this variant.
  • A1298C. There are limited research studies for this variant. A 2004 study focused on 120 blood donors of Irish heritage. Of the donors, 56 or 46.7 percent were heterozygous for this variant and 11 or 14.2 percent were homozygous.
  • Both C677T and A1298C. It�s also possible for people to have both C677T and A1298C MTHFR gene mutation variations, which includes one copy of each.

 

What are the Symptoms of an MTHFR Gene Mutation?

 

Symptoms of an MTHFR gene mutation can be different from person to person and from variant to variant. It’s important to remember that further research around MTHFR gene mutation variants and their effects on health are still needed. Evidence regarding how MTHFR gene mutation variants are associated with a variety of other health issues is currently lacking or it has been disproven. Conditions that have been suggested to be associated with MTHFR variants include:

 

  • anxiety
  • depression
  • bipolar disorder
  • schizophrenia
  • migraines
  • chronic pain and fatigue
  • nerve pain
  • recurrent miscarriages in women of child-bearing age
  • pregnancies with neural tube defects, like spina bifida and anencephaly
  • cardiovascular and thromboembolic diseases (blood clots, stroke, embolism, and heart attacks)
  • acute leukemia
  • colon cancer

What is the MTHFR Diet?

 

According to healthcare professionals, eating foods with high amounts of folate may help naturally support low folate levels in the bloodstream associated with MTHFR gene mutation variants.�Good food choices can include:

 

  • fruits, such as strawberries, raspberries, grapefruit, cantaloupe, honeydew, banana.
  • juices like orange, canned pineapple, grapefruit, tomato, or other vegetable juice
  • veggies, such as spinach, asparagus, lettuce, beets, broccoli, corn, Brussels sprouts, and bok choy
  • proteins, including cooked beans, peas, and lentils
  • peanut butter
  • sunflower seeds

 

People with MTHFR gene mutations may also want to avoid eating foods that have the synthetic form of folate, folic acid, however, the evidence is not clear if that�s beneficial or necessary. Supplementation may still be recommended for people with MTHFR gene mutation variants. Furthermore, always make sure to check the labels of the foods you buy, as this vitamin is added to many enriched grains like pasta, cereals, bread, and commercially produced flours.

 

For information regarding the MTHFR and its effects on health issues like cancer, please review this article:

Folate, Methyl-Related Nutrients, Alcohol, and the MTHFR 677C >T Polymorphism Affect Cancer Risk: Intake Recommendations

 


 

MTHFR, or methylenetetrahydrofolate reductase, gene mutations may cause high homocysteine levels and low folate levels in the bloodstream. We believe that a variety of health issues, such as inflammation, may be associated with an MTHFR gene mutation. People can have single or multiple MTHFR gene mutations, as well as neither. The different mutations are often referred to as “variants”. People that have a heterozygous or single variant of the MTHFR gene mutation have a decreased risk of developing health issues like inflammation and chronic pain. Moreover, doctors also believe that people that have homozygous or multiple variants of the MTHFR gene mutation may ultimately have an increased risk of disease. The two MTHFR gene mutation variants are�C677T, A1298C, or both C677T and A1298C. Symptoms of an MTHFR gene mutation can be different from person to person and from variant to variant. Following what is referred to as the MTHFR diet can ultimately help improve overall health in people with MTHFR gene mutation variants. Also, adding these foods into a smoothie can be an easy way to add them into your diet. – Dr. Alex Jimenez D.C., C.C.S.T. Insights

 


 

 

Image of protein power smoothie.

 

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!

 


 

Image of leafy greens smoothie.

 

Leafy Greens Hold the Key to Gut Health

 

A unique type of sugar found in leafy greens can help feed our beneficial gut bacteria. Sulfoquinovose (SQ) is the only known sugar molecule to be made up of sulfur, an extremely essential mineral in the human body. The human body uses sulfur to produce enzymes, proteins, and a variety of hormones as well as antibodies for our cells. A fast and easy way to get leafy greens into your diet is to toss a couple of handfuls of them into a delicious smoothie!

 


 

The scope of our information is limited to chiropractic, musculoskeletal, physical medicines, wellness, and sensitive health issues and/or functional medicine articles, topics, and discussions. We use functional health & wellness protocols to treat and support care for injuries or disorders of the musculoskeletal system. Our posts, topics, subjects and insights cover clinical matters, issues, and topics that relate and support directly or indirectly our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require additional explanation as how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at�915-850-0900. The provider(s) Licensed in Texas*& New Mexico*�

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • Marcin, Ashley. �What You Need to Know About the MTHFR Gene.� Healthline, Healthline Media, 6 Sept. 2019, www.healthline.com/health/mthfr-gene#variants.

 

The Connection Between Nutrition & the Epigenome

The Connection Between Nutrition & the Epigenome

Nutrition is considered to be one of the most well-understood environmental factors associated with changes in the epigenome. Nutrients in the foods we eat are processed by our metabolism and turned into energy. One metabolic pathway, however, is responsible for producing methyl groups or fundamental epigenetic marks that regulate our gene expression. Essential nutrients, such as B vitamins, SAM-e (S-Adenosyl methionine), and folic acid are important components in this methylation process. Diets with high amounts of these essential nutrients can quickly change gene expression, especially during early development. In the following article, we will discuss the connection between nutrition and the epigenome.

 

Nutrigenomics and Health

 

Healthcare professionals discuss that when it comes to dealing with health issues like inflammation and chronic pain, understanding how nutrigenomics affects our overall health is important. Nutritional genomics, or nutrigenomics, is a science that studies the relationship between nutrition, health, and the genome. Researchers in the nutrigenomics field believe that changes in epigenetic marks may be associated with a variety of health issues, including inflammation or the development of diseases like obesity, heart problems, and cancer. Studies have demonstrated that we may be able to control the effects of the nutrients we eat in order to change gene expression associated with various health issues.

 

Approximately more than 1 out of 3 adults in the United States have been diagnosed with obesity which ultimately increases the risk of a variety of health issues, including prediabetes and type 2 diabetes, among other diseases. Previous studies have demonstrated that changes in epigenetic marks during early development may even predispose individuals to obesity. Moreover, changes in epigenetic marks were also demonstrated to affect metabolic pathways that may increase the risk of prediabetes and type 2 diabetes. Healthcare professionals in the nutrigenomics field have created new ways to be able to better find balance through a wholesome understanding of nutrition and the epigenome.

 

“An epigenetic test can provide data that is useful for healthcare professionals. It may also offer information about how certain metabolic pathways are affected by essential nutrients, such as vitamins and minerals”.

 

What is the Epigenetics Diet?

 

The term “epigenetics diet” was first coined by Dr. Trygve Tollefsbol in 2011. It is medically defined as a group of compounds, such as resveratrol in red grapes, genistein in soybeans, isothiocyanates in broccoli, and many other well-known types of foods, which have been demonstrated to help change epigenomic marks and gene expression. According to researchers, the epigenetics diet can prevent the progression of tumors by regulating enzymes that control these epigenomic marks and gene expression, including DNA methyltransferases, histone deacetylases, and certain non-coding RNAs. Several types of foods included in the epigenetics diet are demonstrated in the following infographic:

 

Image of the epigenetic diet.

 

Researchers used recently advanced technologies that demonstrated how several bioactive compounds may aggravate damage to the epigenome caused by environmental pollutions. By way of instance, dietary supplementation with methyl donors, such as vitamin B12, choline, and folate, among others, as well as the isoflavone genistein, can regulate changes to epigenome marks and gene expression caused by bisphenol A, a hormone-disrupting chemical. B vitamins may also prevent the loss of DNA methylation caused by air pollution. According to these same studies, dietary supplementation with folic acid has also been demonstrated to help prevent the negative side-effects caused by heavy metals.

 

We believe that foods in the epigenetics diet could be used to counteract changes to gene expression and epigenomic marks caused by environmental pollution. Environmental pollutants in several types of foods, such as pesticides in fruits like strawberries and leafy greens like spinach, bisphenol A in the plastic containers of foods and drinks, dioxins in fatty foods, polycyclic aromatic hydrocarbons produced when meat is grilled or smoked at high temperatures, and mercury in several types of seafood like king mackerel and swordfish, have been associated with changes to epigenomic marks and gene expression. Those exposures, especially during early development, may cause various health issues.

 

For more information regarding the connection between nutrition and the epigenome, please review this article:

Nutrition and the Epigenome

 


 

Nutrition is one of the most understood environmental factors associated with changes in epigenomic marks and gene expression. Essential nutrients found in the different types of foods we eat are metabolized and turned into molecules in order to be used for energy by the human body. One metabolic pathway is responsible for creating methyl groups, important epigenetic marks that regulate our gene expression and epigenomic marks. Essential nutrients, including B vitamins, SAM-e (S-Adenosyl methionine), and folic acid are fundamental components in DNA methylation. Diets that are rich in these essential nutrients can quickly change epigenetic marks and gene expression, especially during early development. Furthermore, adding a variety of good foods to a smoothie can be a fast and easy way to add essential nutrients to your diet. Below is a fast and easy smoothie recipe to help feed your genes. – Dr. Alex Jimenez D.C., C.C.S.T. Insights

 


 

Image of ginger greens juice.

 

Ginger Greens Juice

Servings: 1
Cook time: 5-10 minutes

� 1 cup pineapple cubes
� 1 apples, 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.

 


 

Image of smoothie with nasturtium flower and leaves.

 

Add Nasturtium to Your Smoothies

 

Adding nasturtium flowers and leaves to any smoothie can add extra nutrients. These lovely plants are easy to grow and the entire plant is edible. Nasturtium leaves are high in vitamin C, which is essential for a healthy immune system, and they also contain calcium, potassium, phosphorus, zinc, copper, and iron. According to healthcare professionals, the extract from the flowers and leaves have antimicrobial, antifungal, hypotensive, expectorant, and anticancer effects. Antioxidants in garden nasturtium occur due to its high content of compounds such as anthocyanins, polyphenols, and vitamin C. Due to its rich phytochemical content and unique elemental composition, the garden nasturtium may be used in the treatment of a variety of health issues, including respiratory and digestive problems. Not to mention, the flowers and leaves look absolutely lovely in smoothies.

 


 

The scope of our information is limited to chiropractic, musculoskeletal, and nervous health issues or functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or disorders of the musculoskeletal system. Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. To further discuss the subject matter above, please feel free to ask�Dr. Alex Jimenez�or contact us at�915-850-0900.

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • Kirkpatrick, Bailey. �Epigenetics, Nutrition, and Our Health: How What We Eat Could Affect Tags on Our DNA.� What Is Epigenetics?, What Is Epigenetics? Media, 11 May 2018, www.whatisepigenetics.com/epigenetics-nutrition-health-eat-affect-tags-dna/.
  • Li, Shizhao, et al. �The Epigenetics Diet: A Barrier against Environmental Pollution.� On Biology, BMC Media, 23 May 2019, blogs.biomedcentral.com/on-biology/2019/05/20/the-epigenetics-diet-a-barrier-against-environmental-pollution/.
  • Learn. Genetics Staff. �Nutrition & the Epigenome.� Learn. Genetics, Learn. Genetics Media, learn.genetics.utah.edu/content/epigenetics/nutrition/.

 

Nutrigenomics and Traits Between Generations

Nutrigenomics and Traits Between Generations

Researchers are trying to understand how nutrigenomics can affect a person’s health. Studies have shown that epigenetics increases the risk of several health issues. Other studies have also shown that nutrition can change the risk of disease. For many years, researchers have studied the way that traits in plants and animals are passed down between generations. However, this process is still not well understood. A recent study evaluated how epigenetic marks are passed down between generations of pregnant rats given personalized nutrition. The findings showed both genetic and characteristics changes in the rats’ offspring. This suggests that maternal traits and diet may send different signals to the fetus.

 

Another study showed methylation changes in mice given more methyl donor intakes over six generations. These findings demonstrated that genetic and characteristic changes passed down between generations may be how environmental factors affect genes in plants and animals to allow adaptation to different environments.�The purpose of the following article is to discuss how nutrigenomics and traits between generations can ultimately affect a person’s overall well-being.

 

Epigenetics, Nutrition, and Exercise

 

Researchers have determined that the role of epigenetics in health issues like cancer is caused by methylation changes in several different types of genes and it is commonly associated with aging. However, the increased risk of cancer may be due to factors in the person’s immediate course of life where changes in epigenetics may happen years before the development of health issues like cancer. One study found that methylation of the breast-cancer-related gene is associated with the increased risk of early-onset breast cancer. Other studies have shown that resveratrol prevents methylation changes while folic acid affected gene expression associated with changes in methylation and other functions.

 

Eicosapentaenoic acid also caused methylation changes in the tumor suppressor gene associated with leukemia cells. This study demonstrated the effect of a polyunsaturated fatty acid on epigenetics. Another study found that methylation increased in women diagnosed with human papillomavirus that didn’t have cervical intraepithelial neoplasia. The changes in methylation were associated with higher concentrations of folate and cobalamin in the blood stream. Another study also found that methylation changes in the tumor suppressor gene L3MBTL1 were ultimately associated with overall health. Further studies are necessary to determine how nutrition can affect epigenetics and traits between generations.

 

Two studies evaluated the effects of exercise on methylation. One of the studies showed methylation changes in people who participated in physical activities for about 30 minutes every day compared with people who engaged in physical activities for less than 10 minutes every day. In the other study, volunteers who participated in exercise demonstrated changes in methylation and gene expression. These findings suggest that methylation is affected by physical activity.

 

Nutrigenomics and Risk of Health Issues

 

Numerous studies have evaluated the role of epigenetics in people with diabetes. According to researchers, changes in methylation of several genes have been shown to be associated with insulin resistance in patients with diabetes. A single change in gene expression caused significant methylation changes in people with diabetes compared to healthy controls. However, other studies found changes in traits between generations and obesity. Furthermore, methylation changes did happen in people with normal glucose metabolism which then developed impaired glucose homeostasis. Various genes have been shown to be different in people with diabetes compared to healthy controls, according to the studies.

 

According to numerous other studies, twins were found to have increased methylation associated with increased insulin resistance. These findings suggest that epigenetic marks associated with diabetes may occur before symptoms and determine the risk of disease. In conclusion, increasing evidence has demonstrated that nutrition can ultimately cause changes to a person’s epigenetics and how these are associated with the increased risk of developing health issues.

 

For more information regarding how epigenetics affects personalized nutrition, please review this article:

Epigenetics: Are There Implications for Personalised Nutrition?

 

 


 

Healthcare professionals and researchers have demonstrated that we can change our epigenetics and gene expression as well as improve the risk of developing a variety of health issues, including inflammation and cancer, which can ultimately cause chronic pain, by controlling the food we eat and focusing on our nutrigenomics. Starting in the kitchen and then taking it directly to the genes, if we follow balanced nutrition, we will see a significant change in our overall health and well-being. At our clinic, we have the ability to assess your specific genetic factors and what dietary guidelines are best for you. One test we use for this is from DNA life, called DNA Diet. A sample of this report is shown below:�

 

http://www.dnalife.healthcare/wp-content/uploads/2019/06/DNA-Diet-Sample-Report-2019.pdf

 


 

Studies show that nutrition can affect methylation and gene expression. These studies have also found that balanced nutrition can improve how good food affects our overall health and well-being. The following article discussed how our epigenetics can affect traits passed down between generations, including methylation and the risk of disease. Although a good diet is essential it may be difficult for some people to follow. Drinking juices or smoothies can be easy ways to include the balanced nutrition we need to promote our health and well-being. Below, I’ve provided a smoothie recipe so you can address your nutrigenomics from the kitchen to your genes. – Dr. Alex Jimenez D.C., C.C.S.T. Insights

 


 

Image of the Berry Bliss Smoothie

 

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.

 


 

The scope of our information is limited to chiropractic, musculoskeletal, and nervous health issues or functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or disorders of the musculoskeletal system. Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. To further discuss the subject matter above, please feel free to ask�Dr. Alex Jimenez�or contact us at�915-850-0900.

 

Curated by Dr. Alex Jimenez D.C., C.C.S.T.

 

References:

 

  • KA;, Burdge GC;Hoile SP;Lillycrop. �Epigenetics: Are There Implications for Personalised Nutrition?� Current Opinion in Clinical Nutrition and Metabolic Care, U.S. National Library of Medicine, 15 Sept. 2012, pubmed.ncbi.nlm.nih.gov/22878237/.

 

Nutritional Epigenetic Influence And Longevity| El Paso, Tx.

Nutritional Epigenetic Influence And Longevity| El Paso, Tx.

Can nutritional epigenetics influence how we age and our longevity? El Paso, Tx. Dr. Jimenez presents data on how nutrition can influence longevity and how we age.

Longevity or our length of life is dictated by complex factors which include our genetic blueprint, age, health, and environment. This includes nutrition.

 nutritional epigenetics el paso tx.

Gene-nutrient interactions are, partly responsible for regulating metabolic processes that begin and develop conditions like obesity, metabolic syndrome, cardiovascular disease, and cancer.

 nutritional epigenetics el paso tx.

A mechanism of nutrient-gene interaction is the epigenetic involvement of inherited patterns of changes, that are maintained by other mechanisms in DNA, Fig. 1a

Two of these mechanisms are:

 nutritional epigenetics el paso tx.

These mechanisms are considered to play important roles in the way we are shaped physiologically and in the way we age.

The Epigenome

  • Think of DNA in the genome like the hardware of a phone that perform specific actions.
  • The epigenome is the software, (program/s), that tells the hardware what to do.

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The Epigenome Becomes Altered Through Nutrition

Nutrition influences the epigenetic mechanisms responsible for phenotype/trait establishment.

Aging is partly regulated by epigenetic mechanisms.

Although still not fully proven but on the right track was that the availability of folate improved the regeneration of the adult central nervous system after injury through an epigenetic mechanism.

Epigenetic Aging

back pain treatment specialist

During the last couple of years, we witnessed a remarkable increase in the number of studies addressing the relationship between epigenetic alterations and aging. Still in its infancy, and still focusing mainly on brain aging, this research clearly indicated that epigenetic mechanisms are not only responsible, in part, for the aging process but they are also dynamically related with memory formation and maintenance.

Penner MR, Roth TL, Barnes CA, Sweatt JD. An epigenetic hypothesis of aging-related cognitive dysfunction. Front Aging Neurosci 2010; 2:9.

The manipulation of the epigenome for memory improvement became possible through changes in histone acetylation.

 nutritional epigenetics el paso tx.

The Link: Nutrition & Longevity

Research to complete the chain of nutrition to epigenetic changes to how we age is still ongoing.

Present knowledge of the epigenetic roles in nutrition having to do with longevity/aging relies on the structure of three components:

  • Nutritionally guided epigenetic modification
  • Age-related epigenetic changes
  • Comprehensive knowledge of both of these components

The first two are being developed quickly, but the third is the most demanding in terms of design, time, allocation, and cost. This takes more time. But technology/humanity is moving along at a quick pace, as well, because at the end of the day we all want to be healthy.

Therefore, Nutritional intervention, when applied at critical periods (e.g., embryonic and fetal development) is having a profound effect as to how the epigenome gets shaped.

When considering the beginning of chronic disease/s, being able to fight disease/s with food sounds like a win-win. If epigenetic/genomic nutrition can help in figuring out what we need to beat disease/s, then let’s go!

curcumin for chronic pain el paso tx.
Family In Kitchen Making Morning Breakfast Together
Genetic-Epigenetic Nutrition And Our Health | El Paso, TX.

Genetic-Epigenetic Nutrition And Our Health | El Paso, TX.

How does epigenetic and personalized nutrition contribute to optimal health?

Most of us know about unhealthy food how it affects our bodies. They

  • Slow Down Metabolism
  • Add Weight
  • Clog and harden arteries etc.
epigenetic nutrition health el paso tx.

But now there are foods and food elements that can help us in a way and comes from a place we might not of thought of, and that is our DNA.

Nutriepigenomics examines connections between diet and biomarkers that can be attached or removed from our DNA. This turns our genes on or off.

New studies are showing that certain foods or supplements can adjust the expression of our genes, which can influence our health.

Nutritional genomics is revolutionizing both clinical and public health nutritional practices:

Diet, exercise, and environmental exposure are all elements that have shown a role in switching genes on and off through epigenetics. Adjusting lifestyle factors can control the potential to reduce disease and have a positive impact on our health.

Health professionals from all over are beginning to incorporate epigenetics into their practice aiming to provide more specialized and individualized treatment plans.

back pain treatment specialist

�Layering information such as diet, lifestyle, environmental factors, family history, symptoms, and diagnoses along with epigenetics can help guide someone to a state of optimized health,� said Kristy Hall, MS, RNCP, ROHP, a board certified functional nutritionist and founder of Living Well Nutrition who uses epigenetic testing, nutrition counseling, and a multifaceted approach to better provide for her clients.


May 15, 2018Bailey Kirkpatrick DietDiseases & DisordersEnvironmentNews & Reviews
nutritional strategies

Registered dietitians have the opportunity to make genetically driven dietary recommendations that can improve human health.

Nutrition is one of the primary environmental factors that determine our health. Chronic diseases include:

  • Type 2 diabetes
  • Metabolic syndrome
  • Cardiovascular disease
  • Neurological disease
  • Various Cancers
  • Are initiated or accelerated by nutrient/food

This field of nutritional research can be referred to as Nutritional Genomics.

Single nucleotide polymorphisms (SNPs) are single base-pair differences in DNA. They represent a primary form of human genetic variation.

Dna SNP

The upper DNA molecule differs from the lower DNA molecule at a single base-pair location (a C/A polymorphism)

Nutritional genetics or nutrigenetics involves the identification, classification, and characterization of human genetic variation that modifies nutrient metabolism/ utilization and food tolerances Fig1.

epigenetic nutrition health el paso tx.
IOM. Nutrigenomics and beyond: Informing the future. Washington, DC: The National Academies Press; 2007.

Application: Genetic & Epigenetics

Nutrients, for example, pharmaceuticals, are powerful effectors of genome expression and stability, and these gene-nutrient interactions can be optimized for disease prevention.

epigenetic nutrition health el paso tx.

Individualized Nutrition

The promise of nutritional engineering for optimal health through diet is still ongoing, but the public is holding positive expectations, as is evidenced by the use of dietary supplements.

Scientific research is showing that nutrients in different foods and supplements we eat may be able to adjust or reverse heritable changes. This evidence can be used in making better lifestyle choices.

Blueberries are incredibly high in antioxidants and it�s thought that this �superfood� can epigenetically reduce DNA damage, thereby protecting humans against cancer and possibly even slow aging. Blueberry juice and vitamin C have been shown to be potential methylation inhibitors for the MTHFR gene and the DNMT1 gene in humans.


Kim, M., Na, H., Kasai, H., Kawai, K., Li, Y.-S., & Yang, M. (2017). Comparison of Blueberry (Vaccinium spp.) and Vitamin C via Antioxidative and Epigenetic Effects in Human. Journal of Cancer Prevention, 22(3), 174�181.

Learning about what we eat and what it does to our bodies, especially potential epigenetic impact, is just one step closer to optimal health.

The Role Of Epigenetics In Obesity And Metabolic Disease

The Role Of Epigenetics In Obesity And Metabolic Disease

Epigenetic Abstract:

The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high-fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying mechanisms are also addressed. In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time. While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

Keywords: Epigenetics, DNA methylation, Obesity, Type 2 diabetes, Developmental programming

Introduction

Epigenetic mechanismsObesity is a complex, multifactorial disease, and better understanding of the mechanisms underlying the interactions between lifestyle, environment, and genetics is critical for developing effective strategies for prevention and treatment [1].

In a society where energy-dense food is plentiful and the need for physical activity is low, there is a wide variation in individuals� susceptibility to develop�obesity and metabolic health problems. Estimates of the role of heredity in this variation are in the range of 40�70 %, and while large genome-wide association studies (GWAS) have identified a number of genetic loci associated with obesity risk, the ~100 most common genetic variants only account for a few percent of variance in obesity [2, 3]. Genome-wide estimates are higher, accounting for ~20 % of the variation [3]; however, a large portion of the heritability remains unexplained.

Recently, attention has turned to investigating the role of epigenetic changes in the etiology of obesity. It has been argued that the epigenome may represent the mechanistic link between genetic variants and environmental�factors in determining obesity risk and could help explain the �missing heritability.� The first human epigenetic studies were small and only investigated a limited number of loci. While this generally resulted in poor reproducibility, some of these early findings, for instance the relationship between PGC1A methylation and type 2 diabetes mellitus (T2DM) [4] and others as discussed in van Dijk et al. [5], have been replicated in later studies. Recent advances and increased affordability of high- throughput technologies now allow for large-scale epigenome wide association studies (EWAS) and integration of different layers of genomic information to explore the complex interactions between the genotype, epigenome, transcriptome, and the environment [6�9]. These studies are still in their infancy, but the results thus far have shown promise in helping to explain the variation in obesity susceptibility.

There is increasing evidence that obesity has develop mental origins, as exposure to a suboptimal nutrient supply before birth or in early infancy is associated with an increased risk of obesity and metabolic disease in later life [10�13]. Initially, animal studies demonstrated that a range of early life nutritional exposures, especially those experienced early in gestation, could induce epigenetic changes in key metabolic tissues of the offspring that persisted after birth and result in permanent alterations in gene function [13�17]. Evidence is emerging to support the existence of the same mechanism in humans. This has led to a search for epigenetic marks present early in life that predict later risk of metabolic disease, and studies to determine whether epigenetic programming of metabolic disease could be prevented or reversed in later life.

This review provides an update of our previous systematic review of studies on epigenetics and obesity in humans [5]. Our previous review showcased the promising outcomes of initial studies, including the first potential epigenetic marks for obesity that could be detected at birth (e.g., RXRA) [18]. However, it also highlighted the limited reproducibility of the findings and the lack of larger scale longitudinal investigations. The current review focuses on recent developments in this rapidly moving field and, in particular, on human EWAS and studies investigating the impact of (pre- and postnatal) nutritional and lifestyle factors on the epigenome and the emerging role of epigenetics in the pathology of obesity. We also address the difficulties in identifying causality in these studies and the importance of animal models in providing insight into mechanisms.

Review

Epigenetic Changes In Animal Models Of Obesity

rabbit eatingAnimal models provide unique opportunities for highly controlled studies that provide mechanistic insight into�the role of specific epigenetic marks, both as indicators of current metabolic status and as predictors of the future risk of obesity and metabolic disease. A particularly important aspect of animal studies is that they allow for the assessment of epigenetic changes within target tissues, including the liver and hypothalamus, which is much more difficult in humans. Moreover, the ability to harvest large quantities of fresh tissue makes it possible to assess multiple chromatin marks as well as DNA methylation. Some of these epigenetic modifications either alone or in combination may be responsive to environmental programming. In animal models, it is also possible to study multiple generations of offspring and thus enable differentiation between trans-generational and intergenerational transmission of obesity risk mediated by epigenetic memory of parental nutritional status, which cannot be easily distinguished in human studies. We use the former term for meiotic transmission of risk in the absence of continued exposure while the latter primarily entails direct transmission of risk through metabolic reprogramming of the fetus or gametes.

Animal studies have played a critical role in our current understanding of the role of epigenetics in the developmental origins of obesity and T2DM. Both increased and decreased maternal nutrition during pregnancy have been associated with increased fat deposition in offspring of most mammalian species studied to date (reviewed in [11, 13�15, 19]). Maternal nutrition during pregnancy not only has potential for direct effects on the fetus, it also may directly impact the developing oocytes of female fetuses and primordial germ cells of male fetuses and therefore could impact both the off- spring and grand-offspring. Hence, multigenerational data are usually required to differentiate between maternal intergenerational and trans-generational transmission mechanisms.

Table 1 summarizes a variety of animal models that have been used to provide evidence of metabolic and epigenetic changes in offspring associated with the parental plane of nutrition. It also contains information pertaining to studies identifying altered epigenetic marks in adult individuals who undergo direct nutritional challenges. The table is structured by suggested risk transmission type.

table 1(i) Epigenetic Changes In Offspring Associated With Maternal Nutrition During Gestation

Maternal nutritional supplementation, undernutrition, and over nutrition during pregnancy can alter fat deposition and energy homeostasis in offspring [11, 13�15, 19]. Associated with these effects in the offspring are changes in DNA methylation, histone post-translational modifications, and gene expression for several target genes,�especially genes regulating fatty acid metabolism and insulin signaling [16, 17, 20�30]. The diversity of animal models used in these studies and the common metabolic pathways impacted suggest an evolutionarily conserved adaptive response mediated by epigenetic modification. However, few of the specific identified genes and epigenetic changes have been cross-validated in related studies, and large-scale genome-wide investigations have typically not been applied. A major hindrance to comparison of these studies is the different develop mental windows subjected to nutritional challenge, which may cause considerably different outcomes. Proof that the epigenetic changes are causal rather than being associated with offspring phenotypic changes is also required. This will necessitate the identification of a parental nutritionally induced epigenetic �memory� response that precedes development of the altered phenotype in offspring.

(ii)Effects Of Paternal Nutrition On Offspring Epigenetic Marks

baby sleeping holding handsEmerging studies have demonstrated that paternal plane of nutrition can impact offspring fat deposition and epigenetic marks [31�34]. One recent investigation using mice has demonstrated that paternal pre-diabetes leads to increased susceptibility to diabetes in F1 offspring with associated changes in pancreatic gene expression and DNA methylation linked to insulin signaling [35]. Importantly, there was an overlap of these epigenetic changes in pancreatic islets and sperm suggesting germ line inheritance. However, most of these studies, although intriguing in their implications, are limited in the genomic scale of investigation and frequently show weak and somewhat transient epigenetic alterations associated with mild metabolic phenotypes in offspring.

(iii)Potential Trans-generational Epigenetic Changes Promoting Fat Deposition In Offspring

excess nutritionStable transmission of epigenetic information across multiple generations is well described in plant systems and C. elegans, but its significance in mammals is still much debated [36, 37]. An epigenetic basis for grand- parental transmission of phenotypes in response to dietary exposures has been well established, including in livestock species [31]. The most influential studies demonstrating effects of epigenetic transmission impacting offspring phenotype have used the example of the viable yellow agouti (Avy) mouse [38]. In this mouse, an insertion of a retrotransposon upstream of the agouti gene causes its constitutive expression and consequent yellow coat color and adult onset obesity. Maternal transmission through the germ line results in DNA methylation�mediated silencing of agouti expression resulting in wild-type coat color and lean phenotype of the offspring [39, 40]. Importantly, subsequent studies in these mice demonstrated that maternal exposure to methyl donors causes a shift in coat color [41]. One study has reported transmission of a phenotype to the F3 generation and alterations in expression of large number of genes in response to protein restriction in F0 [42]; however, alterations in expression were highly variable and a direct link to epigenetic changes was not identified in this system.

(iv) Direct Exposure Of Individuals To Excess Nutrition In Postnatal Life

modern western lifestyleWhile many studies have identified diet-associated epigenetic changes in animal models using candidate site-specific regions, there have been few genome-wide analyses undertaken. A recent study focussed on determining the direct epigenetic impact of high-fat diets/ diet-induced obesity in adult mice using genome-wide gene expression and DNA methylation analyses [43]. This study identified 232 differentially methylated regions (DMRs) in adipocytes from control and high-fat fed mice. Importantly, the corresponding human regions for the murine DMRs were also differentially methylated in adipose tissue from a population of obese and lean humans, thereby highlighting the remarkable evolutionary conservation of these regions. This result emphasizes the likely importance of the identified DMRs in regulating energy homeostasis in mammals.

Human Studies

anatomy 3D model

Drawing on the evidence from animal studies and with the increasing availability of affordable tools for genome- wide analysis, there has been a rapid expansion of epigenome studies in humans. These studies have mostly focused on the identification of site-specific differences in DNA methylation that are associated with metabolic phenotypes.

A key question is the extent to which epigenetic modifications contribute to the development of the metabolic phenotype, rather than simply being a con- sequence of it (Fig. 1). Epigenetic programming could contribute to obesity development, as well as playing a role in consequent risk of cardiovascular and metabolic problems. In human studies, it is difficult to prove causality [44], but inferences can be made from a number of lines of evidence:

fig 1(i) Genetic association studies. Genetic polymorphisms that are associated with an increased risk of developing particular conditions are a priori linked to the causative genes. The presence of differential�methylation in such regions infers functional relevance of these epigenetic changes in controlling expression of the proximal gene(s). There are strong cis-acting genetic effects underpinning much epigenetic variation [7, 45], and in population-based studies, methods that use genetic surrogates to infer a causal or mediating role of epigenome differences have been applied [7, 46�48]. The use of familial genetic information can also lead to the identification of potentially causative candidate regions showing phenotype-related differential methylation [49].

(ii)Timing of epigenetic changes. The presence of an epigenetic mark prior to development of a phenotype is an essential feature associated with causality. Conversely, the presence of a mark in association with obesity, but not before its development, can be used to exclude causality but would not exclude a possible role in subsequent obesity-related pathology.

(iii)Plausible inference of mechanism. This refers to epigenetic changes that are associated with altered expression of genes with an established role in regulating the phenotype of interest. One such example is the association of methylation at two CpG sites at the CPT1A gene with circulating triglyceride levels [50]. CPT1A encodes carnitine palmitoyltransferase 1A, an enzyme with a central role in fatty acid metabolism, and this is strongly indicative that differential methylation of this gene may be causally related to the alterations in plasma triglyceride concentrations.

Epigenome-Wide Association Studies: Identifying Epigenetic Biomarkers Of Metabolic Health

A number of recent investigations have focused on exploring associations between obesity/metabolic diseases�and DNA methylation across the genome (Table 2). The largest published EWAS so far, including a total of 5465 individuals, identified 37 methylation sites in blood that were associated with body mass index (BMI), including sites in CPT1A, ABCG1, and SREBF1 [51]. Another large-scale study showed consistent associations between BMI and methylation in HIF3A in whole blood and adipose tissue [52], a finding which was also partially replicated in other studies [9, 51]. Other recently reported associations between obesity-related measures and DNA methylation include (i) DNA methylation differences between lean and obese individuals in LY86 in blood leukocytes [53]; (ii) associations between PGC1A promoter methylation in whole blood of children and adiposity 5 years later [54]; (iii) associations between waist-hip ratio and ADRB3 methylation in blood [55]; and (iv) associations between BMI, body fat distribution measures, and multiple DNA methylation sites in adipose tissue [9, 56]. EWAS have also shown associations between DNA methylation sites and blood lipids [55, 57�59], serum metabolites [60], insulin resistance [9, 61], and T2DM [48, 62, 63] (Table 2).

table 2 contdFrom these studies, altered methylation of PGC1A, HIF3A, ABCG1, and CPT1A and the previously described RXRA [18] have emerged as biomarkers associated with, or perhaps predictive of, metabolic health that are also plausible candidates for a role in development of metabolic disease.

Interaction Between Genotype And The Epigenome

Genotype EpigenomeEpigenetic variation is highly influenced by the underlying genetic variation, with genotype estimated to explain ~20�40 % of the variation [6, 8]. Recently, a number of studies have begun to integrate methylome and genotype data to identify methylation quantitative trait loci (meQTL) associated with disease phenotypes. For instance, in adipose tissue, an meQTL overlapping�with a BMI genetic risk locus has been identified in an enhancer element upstream of ADCY3 [8]. Other studies have also identified overlaps between known obesity and T2DM risk loci and DMRs associated with obesity and T2DM [43, 48, 62]. Methylation of a number of such DMRs was also modulated by high-fat feeding in mice [43] and weight loss in humans [64]. These results identify an intriguing link between genetic variations linked with disease susceptibility and their association with regions of the genome that undergo epigenetic modifications in response to nutritional challenges, implying a causal relationship. The close connection between genetic and epigenetic variation may signify their essential roles in generating individual variation [65, 66]. However, while these findings suggest that DNA methylation may be a mediator of genetic effects, it is also important to consider that both genetic and epigenetic processes could act independently on the same genes. Twin studies [8, 63, 67] can provide important insights and indicate that inter-individual differences in levels of DNA methylation arise predominantly from non-shared environment and stochastic influences, minimally from shared environmental effects, but also with a significant impact of genetic variation.

The Impact Of The Prenatal And Postnatal Environment On The Epigenome

fetus modelPrenatal environment: Two recently published studies made use of human populations that experienced �natural� variations in nutrient supply to study the impact of maternal nutrition before or during pregnancy on DNA methylation in the offspring [68, 69]. The first study used a Gambian mother-child cohort to show that both seasonal variations in maternal methyl donor intake during pregnancy and maternal pre-pregnancy BMI were associated with altered methylation in the infants [69]. The second study utilized adult offspring from the Dutch Hunger Winter cohort to investigate the effect of prenatal exposure to an acute period of severe maternal undernutrition on DNA methylation of genes involved in growth and metabolism in adulthood [68]. The results highlighted the importance of the timing of the exposure in its impact on the epigenome, since significant epigenetic effects were only identified in individuals exposed to famine during early gestation. Importantly, the epigenetic changes occurred in conjunction with increased BMI; however, it was not possible to establish in this study whether these changes were present earlier in life or a consequence of the higher BMI.

Other recent studies have provided evidence that prenatal over-nutrition and an obese or diabetic maternal environment are also associated with DNA methylation changes in genes related to embryonic development, growth, and metabolic disease in the offspring [70�73].

While human data are scarce, there are indications that paternal obesity can lead to altered methylation of imprinted genes in the newborn [74], an effect thought to be mediated via epigenetic changes acquired during spermatogenesis.

baby walking in the grass and mudPostnatal environment: The epigenome is established de novo during embryonic development, and therefore, the prenatal environment most likely has the most significant impact on the epigenome. However, it is now clear that changes do occur in the �mature� epigenome under the influence of a range of conditions, including aging, exposure to toxins, and dietary alterations. For example, changes in DNA methylation in numerous genes in skeletal muscle and PGC1A in adipose tissue have been demonstrated in response to a high-fat diet [75, 76]. Interventions to lose body fat mass have also been associated with changes in DNA methylation. Studies have reported that the DNA methylation profiles of adipose tissue [43, 64], peripheral blood mononuclear cells [77], and muscle tissue [78] in formerly obese patients become more similar to the profiles of lean subjects following weight loss. Weight loss surgery also partially reversed non-alcoholic fatty liver disease-associated methylation changes in liver [79] and in another study led to hypomethylation of multiple obesity candidate genes, with more pronounced effects in subcutaneous compared to omental (visceral) fat [64]. Accumulating evidence suggests that exercise interventions can also influence DNA methylation. Most of these studies have been conducted in lean individuals [80�82], but one exercise study in obese T2DM subjects also demonstrated changes in DNA methylation, including in genes involved in fatty acid and glucose transport [83]. Epigenetic changes also occur with aging, and recent data suggest a role of obesity in augmenting them [9, 84, 85]. Obesity accelerated the epigenetic age of liver tissue, but in contrast to the findings described above, this effect was not reversible after weight loss [84].

Collectively, the evidence in support of the capacity to modulate the epigenome in adults suggests that there may be the potential to intervene in postnatal life to modulate or reverse adverse epigenetic programming.

Effect Sizes And Differences Between Tissue Types

connective tissuesDNA methylation changes associated with obesity or induced by diet or lifestyle interventions and weight loss are generally modest (<15 %), although this varies depending on the phenotype and tissue studied. For instance, changes greater than 20 % have been reported in adipose tissue after weight loss [64] and associations between HIF3A methylation and BMI in adipose tissue were more pronounced than in blood [52].

The biological relevance of relatively small methylation changes has been questioned. However, in tissues consisting of a mixture of cell types, a small change in DNA methylation may actually reflect a significant change in a specific cell fraction. Integration of epigenome data with transcriptome and other epigenetic data, such as histone modifications, is important, since small DNA methylation changes might reflect larger changes in chromatin structure and could be associated with broader changes in gene expression. The genomic context should also be considered; small changes within a regulatory element such as a promotor, enhancer, or insulator may have functional significance. In this regard, DMRs for obesity, as well as regions affected by prenatal famine exposure and meQTL for metabolic trait loci have been observed to overlap enhancer elements [8, 43, 68]. There is evidence that DNA methylation in famine-associated regions could indeed affect enhancer activity [68], supporting a role of nutrition-induced methylation changes in gene regulation.

A major limitation in many human studies is that epigenetic marks are often assessed in peripheral blood, rather than in metabolically relevant tissues (Fig. 2). The heterogeneity of blood is an issue, since different cell populations have distinct epigenetic signatures, but algorithms have been developed to estimate the cellular composition to overcome this problem [86]. Perhaps more importantly, epigenetic marks in blood cells may not necessarily report the status of the tissues of primary interest. Despite this, recent studies have provided clear evidence of a relationship between epigenetic marks in blood cells and BMI. In the case of HIF3A for which the level of methylation (beta-value) in the study population ranged from 0.14�0.52, a 10 % increase in methylation was associated with a BMI increase of 7.8 %�[52]. Likewise, a 10 % difference in PGC1A methylation may predict up to 12 % difference in fat mass [54].

fig 2Conclusions

The study of the role of epigenetics in obesity and metabolic disease has expanded rapidly in recent years, and evidence is accumulating of a link between epigenetic modifications and metabolic health outcomes in humans. Potential epigenetic biomarkers associated with obesity and metabolic health have also emerged from recent studies. The validation of epigenetic marks in multiple cohorts, the fact that several marks are found in genes with a plausible function in obesity and T2DM development, as well as the overlap of epigenetic marks with known obesity and T2DM genetic loci strengthens the evidence that these associations are real. Causality has so far been difficult to establish; however, regardless of whether the associations are causal, the identified epigenetic marks may still be relevant as biomarkers for obesity and metabolic disease risk.

Effect sizes in easily accessible tissues such as blood are small but do seem reproducible despite variation in ethnicity, tissue type, and analysis methods [51]. Also, even small DNA methylation changes may have biological significance. An integrative �omics� approach will be crucial in further unraveling the complex interactions between the epigenome, transcriptome, genome, and metabolic health. Longitudinal studies, ideally spanning multiple generations, are essential to establishing causal relationships. We can expect more such studies in the future, but this will take time.

While animal studies continue to demonstrate an effect of early life nutritional exposure on the epigenome and metabolic health of the offspring, human data are still limited. However, recent studies have provided clear�evidence that exposure to suboptimal nutrition during specific periods of prenatal development is associated with methylation changes in the offspring and therefore have the potential to influence adult phenotype. Animal studies will be important to verify human findings in a more controlled setting, help determine whether the identified methylation changes have any impact on metabolic health, and unravel the mechanisms underlying this intergenerational/transgenerational epigenetic regulation. The identification of causal mechanisms underlying metabolic memory responses, the mode of transmission of the phenotypic effects into successive generations, the degree of impact and stability of the transmitted trait, and the identification of an overarching and unifying evolutionary context also remain important questions to be addressed. The latter is often encapsulated by the predictive adaptive response hypothesis, i.e., a response to a future anticipated environment that increases fitness of the population. However, this hypothesis has increasingly been questioned as there is limited evidence for increased fitness later in life [87].

In summary, outcomes are promising, as the epigenetic changes are linked with adult metabolic health and they act as a mediator between altered prenatal nutrition and subsequent increased risk of poor metabolic health outcomes. New epigenetic marks have been identified that are associated with measures of metabolic health. Integration of different layers of genomic information has added further support to causal relationships, and there have been further studies showing effects of pre- and postnatal environment on the epigenome and health. While many important questions remain, recent methodological advances have enabled the types of large-scale population-based studies that will be required to address the knowledge gaps. The next decade promises to be a period of major activity in this important research area.

Susan J. van Dijk1, Ross L. Tellam2, Janna L. Morrison3, Beverly S. Muhlhausler4,5� and Peter L. Molloy1*�

Competing interests

The authors declare that they have no competing interests.

Authors� contributions
All authors contributed to the drafting and critical revision of the manuscript, and all authors read and approved the final manuscript.

Authors� information
Beverly S. Muhlhausler and Peter L. Molloy are joint last authors.

Acknowledgements

This work has been supported by a grant from the Science and Industry Endowment Fund (Grant RP03-064). JLM and BSM are supported by the National Health and Medical Research Council Career Development Fellowships (JLM, APP1066916; BSM, APP1004211). We thank Lance Macaulay and Sue Mitchell for critical reading and comments on the manuscript.

Author details

1CSIRO Food and Nutrition Flagship, PO Box 52, North Ryde, NSW 1670, Australia. 2CSIRO Agriculture Flagship, 306 Carmody Road, St Lucia, QLD 4067, Australia. 3Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia�4FOODplus Research Centre, Waite Campus, The University of Adelaide, PMB 1, Glen Osmond, SA 5064, Australia. 5Women�s and Children�s Health Research Institute, 72 King William Road, North Adelaide, SA 5006, Australia.

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