#MTHFR and health risks | Explore Tumblr posts and blogs

adorshea11 · 10 months ago

Text

Calcium L-Methylfolate as a Source of Folate

In the realm of nutritional science, the significance of folate, a B-vitamin crucial for cell development, cannot be overstated. Folic acid, the synthetic form of folate, is utilized in various supplements, including L-Methylfolate Calcium, to address and prevent folate deficiencies. This blog aims to explore the vital role of Calcium L-Methylfolate as a source of folate, delving into its applications, dosage, regulations, and potential interactions with other drugs. Let's embark on a comprehensive journey into the world of folate and its synthetic counterpart, L-Methylfolate Calcium.

Understanding Folate and Folic Acid:

Folate, a naturally occurring B-vitamin found in certain foods, is essential for the formation of healthy cells, particularly red blood cells. Folic acid, on the other hand, is the synthetic form of folate commonly used in supplements. These supplements, including L-Methylfolate Calcium, are prescribed to treat or prevent low folate levels, which can lead to various health issues such as anemia.

Conditions leading to low folate levels encompass a range of factors, from poor dietary choices and alcoholism to pregnancy and specific medical conditions like liver disease or kidney dialysis. Notably, women of childbearing age are advised to ensure sufficient folic acid intake, either through their diet or supplements, to prevent spinal cord birth defects in infants.

How to Use L-Methylfolate Calcium:

The administration of L-Methylfolate Calcium is a critical aspect of its efficacy. Whether taken with or without food, it is imperative to follow the doctor's instructions, typically once daily. Over-the-counter products also come with specific directions on the package, emphasizing the importance of adhering to guidelines provided by healthcare professionals. Dosage adjustments should only be made under the supervision of a medical practitioner, and regular intake is crucial for optimal benefits.

Folate Regulation and Genetic Polymorphisms:

The term "folate" encompasses B vitamins, including folic acid and active pteroylglutamates. The hydrolysis of folates occurs in the intestinal jejunum and the liver, leading to the active circulating form, L-Methylfolate. Individuals with genetic polymorphisms for genes coding methylenetetrahydrofolate reductase (MTHFR) may face challenges in metabolizing folic acid efficiently, affecting the vitamin B12 dependent methylation cycle.

It is essential to note that folate, including reduced forms such as folinic acid, may obscure pernicious anemia above certain doses, necessitating supervision by a licensed medical practitioner during administration.

Indications, Contraindications, and Warnings:

L-Methylfolate Calcium 7.5 mg is specifically indicated for addressing the nutritional requirements of patients determined by a licensed medical practitioner. However, it is contraindicated in individuals with known hypersensitivity to any of its ingredients.

Caution is recommended for patients with a history of bipolar illness. Folate therapy alone is insufficient for treating vitamin B12 deficiency, and it is crucial to screen patients with depressive symptoms for potential bipolar disorder risks.

Drug Interactions and Precautions:

The drug interactions and precautions associated with L-Methylfolate Calcium are critical aspects that healthcare professionals must consider when prescribing this supplement. Understanding these interactions ensures the safety and efficacy of the treatment, preventing potential adverse effects. Let's delve deeper into the specific drug interactions and precautions associated with L-Methylfolate Calcium:

Antiepileptic Drugs (AED):

L-Methylfolate Calcium may interact with antiepileptic drugs, such as phenytoin, carbamazepine, primidone, valproic acid, fosphenytoin, valproate, phenobarbital, and lamotrigine.

Caution is warranted due to the potential impairment of folate absorption and increased metabolism of circulating folate. Enhanced phenytoin metabolism may lead to lower blood levels, potentially allowing breakthrough seizures.

Capecitabine:

Interaction with capecitabine may increase its toxicity when combined with L-Methylfolate Calcium. Caution is advised to avoid adverse effects and ensure patient safety during cancer treatment.

Cholestyramine:

The co-administration of cholestyramine with L-Methylfolate Calcium may reduce folic acid absorption and serum folate levels. Monitoring and adjustments in dosage may be necessary to maintain optimal folate levels.

Phenytoin and Other Anticonvulsants:

Caution is particularly emphasized when prescribing L-Methylfolate Calcium alongside phenytoin and other anticonvulsants. Enhanced phenytoin metabolism may compromise the therapeutic levels of antiepileptic medications, necessitating close monitoring and potential dosage adjustments.

Healthcare professionals should thoroughly review a patient's medical history, current medications, and potential drug interactions before prescribing L-Methylfolate Calcium. Individualized treatment plans and close monitoring are crucial to ensuring the safety and efficacy of this supplement, especially in populations susceptible to interactions or with specific medical conditions. As with any prescription, open communication between healthcare providers and patients is essential to address concerns, monitor for adverse effects, and optimize the overall success of the treatment regimen.

The blog also details interactions with oral contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), and other medications, emphasizing the importance of medical supervision and thorough screening before prescribing L-Methylfolate Calcium.

Pregnancy and Nursing Considerations:

While L-Methylfolate Calcium 7.5 mg is not intended as a prenatal/postnatal multivitamin for lactating and non-lactating mothers, its use during pregnancy and lactation should be discussed with a medical practitioner. The reduced form of B vitamin in the product necessitates caution, and consultation with healthcare professionals is crucial for pregnant or lactating individuals.

Adverse Reactions and Dosage Recommendations:

Allergic sensitization to folic acid has been reported, warranting attention during oral or parental administration. The recommended adult dose is 7.5 to 15 mg daily, administered with or without food, as directed by a licensed medical practitioner.

Product Supply and Storage:

L-Methylfolate Calcium 7.5 mg is available in coated, round, blue tablets supplied in bottles of 30 and 90 tablets. Proper storage at controlled room temperature (15°-30°C) is essential to maintain its efficacy.

Conclusion:

In conclusion, Calcium L-Methylfolate proves to be a vital and targeted solution for individuals facing folate deficiencies, offering a synthesized form of the essential B-vitamin necessary for cell development. This comprehensive exploration has shed light on the multifaceted aspects of L-Methylfolate Calcium, emphasizing its role as a source of folate and its applications in diverse medical scenarios.

Understanding the distinction between natural folate and synthetic folic acid becomes imperative, especially when addressing conditions that lead to low folate levels. The necessity of such supplementation is highlighted in cases ranging from poor dietary choices and pregnancy to complex medical conditions like liver disease and kidney dialysis. Notably, the blog emphasizes the critical role of folic acid, particularly in women of childbearing age, to prevent spinal cord birth defects in infants, underscoring the significance of timely intervention.

The dosage and administration guidelines stressed throughout the blog reinforce the importance of medical supervision. Whether taken with or without food, adherence to prescribed dosages is crucial for optimal effectiveness. Moreover, the cautionary notes regarding potential interactions with various drugs, including antiepileptic medications and NSAIDs, stress the need for meticulous screening and supervision by healthcare professionals.

The discussion on folate regulation, genetic polymorphisms, and the potential obscuring of pernicious anemia by certain forms of folate provides valuable insights into the complexity of folate metabolism. The blog urges practitioners to exercise caution and vigilance, especially in populations with specific genetic variations.

As we navigate through the intricacies of L-Methylfolate Calcium, the blog concludes by emphasizing its role in meeting distinct nutritional requirements under licensed medical supervision. Its contraindications, warnings, and precautions underscore the need for a personalized and cautious approach in its prescription. Overall, this exploration into Calcium L-Methylfolate as a source of folate illuminates its significance in the realm of nutritional science, offering targeted solutions for those in need, while also highlighting the importance of informed and supervised use in diverse healthcare contexts.

Source: https://sites.google.com/view/adorshea01/calcium-l-methylfolate-as-a-source-of-folate

#fertility drugs #male fertility medicine #gynec medicine

0 notes

treatmentguidelines · 1 year ago

Text

Homocystinuria

Are you or someone you know living with homocystinuria? In this blog post, we will explore every aspect of this rare genetic disorder, from its definition and causes to its symptoms, diagnosis methods, and available treatment options. Additionally, we will discuss the importance of dietary modifications and regular medical follow-up to manage homocystinuria effectively. We will also touch upon potential complications, support and resources available for patients and families, as well as current research and advancements in the field. Finally, we will provide some valuable lifestyle tips for effectively managing this condition. Stay tuned for a comprehensive guide on homocystinuria management.

What Is Homocystinuria?

Homocystinuria: A Rare Genetic Condition Homocystinuria is a rare genetic condition that affects the body's ability to break down certain amino acids. This inherited disorder prevents the body from properly metabolizing an amino acid called methionine, leading to the build-up of homocysteine in the blood and urine. Homocystinuria is a lifelong condition that can have serious health implications if left untreated. Understanding the causes, symptoms, diagnosis methods, and available treatment options is crucial for individuals living with or caring for someone with homocystinuria. Causes of Homocystinuria: Genetic Mutations and Enzyme Deficiencies Homocystinuria is primarily caused by genetic mutations that affect the enzymes responsible for breaking down methionine. These mutations can be inherited from one or both parents, and each case of homocystinuria may have different underlying genetic causes. The most common form of the condition, known as classical homocystinuria, is caused by a deficiency of an enzyme called cystathionine beta-synthase (CBS). However, other less common forms of homocystinuria can result from deficiencies in enzymes such as methylene tetrahydrofolate reductase (MTHFR) or cobalamin cofactor metabolism (MMACHC). Symptoms and Signs: Recognizing the Red Flags Homocystinuria can manifest in various ways, and the severity of symptoms can vary among individuals. Some common signs and symptoms of homocystinuria include: 1. Developmental delays and intellectual disability. 2. Eye problems, such as nearsightedness, dislocation of the lens, and glaucoma. 3. Skeletal abnormalities, including long limbs, a tall and thin build, and curved spine. 4. Blood clotting abnormalities, which can lead to an increased risk of strokes and other thromboembolic events. 5. Mental health issues, including anxiety, depression, and psychiatric disorders. It is important to note that these symptoms may not always be present at birth and may become more apparent over time. Early diagnosis and intervention can greatly improve outcomes for individuals with homocystinuria. Diagnosis Methods: Unraveling the Genetic Puzzle Diagnosing homocystinuria involves a combination of clinical evaluations, laboratory tests, and genetic testing. Medical professionals will assess an individual's medical history, perform a physical examination, and conduct various laboratory tests to measure levels of homocysteine and methionine in the blood and urine. Genetic testing may also be recommended to identify specific genetic mutations associated with homocystinuria. Additionally, newborn screening programs have been implemented in many countries to detect homocystinuria shortly after birth, allowing for early intervention and treatment. Diagnosis Methods Overview: Pros: Cons: Clinical Evaluation Can provide initial insights into symptoms and risks. Subjective and may vary depending on the expertise of the clinician. Laboratory Tests Objective measurements of homocysteine and methionine levels. Results may be affected by factors like diet or medications. Genetic Testing Identifies specific genetic mutations. Expensive and potentially time-consuming. Newborn Screening Allows for early detection and intervention. May produce false-positive or false-negative results.

Causes Of Homocystinuria

Homocystinuria is a rare genetic disorder that affects the body's ability to process certain amino acids. This condition results in a buildup of homocysteine, an amino acid, in the blood and urine. Homocystinuria is primarily caused by genetic mutations that affect the enzymes responsible for breaking down homocysteine. These mutations can be inherited from one or both parents, making it an autosomal recessive disorder. One of the most common causes of homocystinuria is a deficiency in one of the enzymes involved in the metabolism of homocysteine. This can be caused by mutations in genes such as CBS, MTHFR, MTR, and MTRR. These mutations can disrupt the normal functioning of the enzyme, leading to the accumulation of homocysteine in the body. In some cases, homocystinuria can also be caused by a deficiency in vitamin B6, which plays a crucial role in the metabolism of homocysteine. This deficiency can be caused by a variety of factors, including a poor diet, malabsorption issues, or certain medications that interfere with the absorption or utilization of vitamin B6. Other less common causes of homocystinuria include deficiencies in other B-vitamins, such as folate and vitamin B12, or defects in the transport mechanisms that allow homocysteine to be efficiently cleared from the body. These abnormalities can also contribute to the accumulation of homocysteine and the development of homocystinuria. Genetic Mutations Vitamin Deficiencies Transport Defects 1. CBS 1. Vitamin B6 deficiency 1. Abnormal homocysteine transporters 2. MTHFR 2. Folate deficiency 2. Impaired homocysteine clearance 3. MTR 3. Vitamin B12 deficiency 4. MTRR In conclusion, homocystinuria is primarily caused by genetic mutations that affect the enzymes responsible for metabolizing homocysteine. Deficiencies in vitamin B6, folate, and vitamin B12, as well as defects in homocysteine transport mechanisms, can also contribute to the development of this rare genetic disorder. Understanding the causes of homocystinuria is crucial for diagnosis and management, as it can help healthcare professionals develop appropriate treatment plans and support for individuals and families affected by this condition.

Symptoms And Signs

Homocystinuria is a rare genetic disorder that affects the body's metabolism of an amino acid called methionine. People with this condition are unable to properly break down methionine, leading to a buildup of homocysteine in the blood and urine. The elevated levels of homocysteine can cause a wide range of symptoms and signs that can vary in severity from person to person. One of the most common symptoms of homocystinuria is developmental delay. Infants with the condition may not reach certain developmental milestones, such as sitting, crawling, or walking, at the expected age. They may also have difficulty with learning and may experience intellectual disability. Another prominent sign of homocystinuria is the appearance of certain physical features. These include tall stature, long limbs, and a thin build. People with the condition may also have a "marfanoid" appearance, with features such as a long, narrow face; a high and narrow palate; and a protruding jaw. In addition to the physical characteristics, individuals with homocystinuria may experience eye-related symptoms. These can include nearsightedness, dislocation of the lens within the eye, and a higher risk of developing glaucoma. If left untreated, these eye problems can lead to vision loss. Other symptoms that may be associated with homocystinuria include seizures, blood clotting abnormalities, and psychiatric disorders such as anxiety and depression. Some individuals may also have an increased risk of developing osteoporosis, a condition characterized by weakened bones. It is important to note that the symptoms and signs of homocystinuria can present differently in each affected individual. Some individuals may only exhibit mild symptoms, while others may have more severe manifestations of the disorder. Early diagnosis and prompt treatment are crucial in managing the symptoms and preventing potential complications associated with homocystinuria.

Diagnosis Methods

Homocystinuria is a rare genetic disorder that affects the body's ability to break down certain proteins. It is caused by a deficiency of an enzyme called cystathionine beta-synthase (CBS), which leads to the buildup of homocysteine in the blood and urine. Early diagnosis is crucial for effective management and treatment of this condition, as it can lead to serious complications if left untreated. In this blog post, we will explore the various diagnostic methods used to identify and confirm the presence of homocystinuria. 1. Newborn Screening: One of the most common methods of diagnosing homocystinuria is through newborn screening programs. This involves collecting a small blood sample from the baby's heel shortly after birth, which is then sent to a laboratory for analysis. The sample is tested for elevated levels of homocysteine and methionine, which can indicate the presence of the disorder. If the initial screening test is positive, further testing is done to confirm the diagnosis. 2. Molecular Genetic Testing: Once a suspicion of homocystinuria is raised based on the symptoms or the results of newborn screening, molecular genetic testing is usually performed to confirm the diagnosis. This involves analyzing the DNA of the patient to identify any mutations or variations in the CBS gene. Genetic testing can help determine the specific type of homocystinuria and provide valuable information for personalized treatment and management strategies. 3. Biochemical Tests: In addition to genetic testing, various biochemical tests can be conducted to evaluate the levels of homocysteine and other related compounds in the body. These tests can include measuring plasma or urine levels of homocysteine, methionine, cystathionine, and other amino acids. Abnormal results can provide further evidence of homocystinuria and help guide treatment decisions. Potential Testing Methods Description Plasma Amino Acid Profiling This test measures the levels of various amino acids, including homocysteine and methionine, in the plasma. Elevated levels can indicate the presence of homocystinuria. Homocysteine Loading Test This test involves administering a high dose of methionine or homocysteine and then measuring the levels of these compounds in the blood over time. It can help evaluate the body's ability to process homocysteine. Enzyme Assays Enzyme assays can be performed to measure the activity of cystathionine beta-synthase (CBS) or other enzymes involved in the metabolism of homocysteine. Reduced enzyme activity may suggest the presence of homocystinuria. Overall, the diagnosis of homocystinuria involves a combination of newborn screening, genetic testing, and biochemical tests. The accurate identification of this disorder is crucial for initiating appropriate treatment and management strategies. If you suspect that you or your child may have homocystinuria, it is important to consult a healthcare professional who can guide you through the diagnostic process and provide the necessary support.

Genetic Testing For Homocystinuria

In the field of genetic medicine, testing plays a crucial role in diagnosing and managing various genetic disorders. One such disorder is Homocystinuria, a rare genetic condition that affects the body's ability to break down an essential amino acid called methionine. Genetic testing for Homocystinuria is an essential tool for identifying the specific genetic mutations responsible for the disorder, allowing healthcare professionals to provide appropriate treatment and counseling for affected individuals and their families. Homocystinuria is an inherited metabolic disorder caused by mutations in one of several different genes involved in the metabolism of methionine. These genetic mutations disrupt the normal processing of methionine, leading to an accumulation of toxic byproducts in the body. Genetic testing can identify the specific gene mutation responsible for Homocystinuria and can help confirm the diagnosis. Genetic testing for Homocystinuria usually involves a blood sample or a cheek swab. The sample is sent to a specialized laboratory where it is analyzed to identify mutations in the genes associated with the condition. This type of testing is highly accurate and can detect even small genetic changes that may contribute to the development of Homocystinuria. - Li: One main advantage of genetic testing for Homocystinuria is its ability to provide a definitive diagnosis. Confirming the presence of specific gene mutations linked to Homocystinuria can help healthcare professionals tailor treatment plans and provide accurate genetic counseling for affected individuals and their families. - Li: Genetic testing also plays a vital role in carrier screening for Homocystinuria. Individuals who carry a mutated gene associated with this disorder have an increased risk of passing it on to their children. Identifying carriers through genetic testing can help couples make informed decisions about family planning and take appropriate measures to reduce the risk of passing on the disorder. - Li: Furthermore, genetic testing can help guide treatment choices for individuals with Homocystinuria. Different gene mutations can affect the severity of symptoms and the responsiveness to specific therapies. Understanding an individual's unique genetic makeup can enable healthcare professionals to develop personalized treatment plans and optimize patient outcomes. In summary, genetic testing plays a crucial role in the diagnosis and management of Homocystinuria. It provides a definitive diagnosis, helps screen for carriers, and guides treatment decisions. With advancements in genetic medicine, healthcare professionals can use this valuable tool to provide tailored care and support to individuals and families affected by Homocystinuria.

Available Treatment Options

When it comes to managing and treating homocystinuria, there are various treatment options available that can help patients lead a healthier life. The primary goal of treatment is to minimize symptoms, prevent complications, and improve the overall quality of life for individuals with this rare genetic disorder. Dietary Modifications: One of the main treatment strategies for homocystinuria involves making dietary modifications. This includes reducing the intake of foods high in methionine, an amino acid that breaks down into homocysteine. This can be achieved by following a low-protein diet and avoiding foods such as meat, eggs, dairy products, and certain beans. Additionally, increasing the intake of pyridoxine (vitamin B6), folic acid, and betaine supplements can help lower homocysteine levels in the body. Medication: In some cases, medication may be prescribed to manage homocystinuria. This can include the use of medications such as pyridoxine (vitamin B6), folate (vitamin B9), and betaine. Pyridoxine helps to convert homocysteine into a less harmful substance, while folate and betaine aid in the breakdown of homocysteine. These medications are usually prescribed based on individual needs and may require regular monitoring of blood homocysteine levels. Pros Cons - Can effectively lower homocysteine levels - May require frequent monitoring and adjustment - Can help manage and prevent complications - May result in the need for lifelong medication - Can be easily incorporated into daily routine - Possible side effects Monitoring and Follow-Up: Regular monitoring of blood homocysteine levels is crucial in managing homocystinuria. This helps determine the effectiveness of treatment and allows for necessary adjustments to the treatment plan. It is important for individuals with homocystinuria to have regular check-ups with their healthcare provider to assess their overall health, monitor potential complications, and ensure proper management of the condition. It is important to note that the treatment options for homocystinuria may vary among individuals based on the severity of the condition, age, and overall health. Consulting with a healthcare professional or a specialist in metabolic disorders is essential to develop a personalized treatment plan that suits the specific needs of each patient.

Dietary Modifications For Homocystinuria

Homocystinuria is a rare genetic disorder that affects the way the body processes certain amino acids, leading to a buildup of homocysteine in the blood. This can result in various health problems, including damage to the heart, blood vessels, eyes, and skeletal system. While there is no cure for homocystinuria, dietary modifications can play a crucial role in managing the condition and preventing complications. One of the key dietary modifications for individuals with homocystinuria is reducing the intake of methionine-rich foods. Methionine is an amino acid that is normally metabolized by the body. However, in people with homocystinuria, the enzyme that breaks down methionine is deficient, leading to an accumulation of homocysteine. To reduce methionine levels, it is important to limit or avoid foods such as meat, poultry, fish, dairy products, eggs, and nuts which are high in methionine. On the other hand, it is important to increase the intake of foods that are low in methionine but high in other essential amino acids. These include fruits, vegetables, whole grains, and legumes. These foods not only provide essential nutrients but also help in maintaining a balanced diet. Additionally, it is recommended to include foods that are rich in vitamin B6, B12, and folate, as these vitamins are essential for homocysteine metabolism. - Include foods that are low in methionine but high in other essential amino acids. - Avoid or limit the intake of methionine-rich foods such as meat, poultry, fish, dairy products, eggs, and nuts. Methionine-Rich Foods Methionine-Low Foods Meat Fruits Poultry Vegetables Fish Whole grains Dairy products Legumes Eggs Nuts It is important for individuals with homocystinuria to work closely with a registered dietitian or nutritionist to develop a personalized meal plan. These professionals can provide guidance on portion sizes, food choices, and ways to ensure adequate intake of essential nutrients while managing methionine levels. They can also help in monitoring the individual's nutritional status and making necessary adjustments to the diet as needed. In addition to dietary modifications, individuals with homocystinuria may also benefit from certain supplements. These may include vitamin B6, B12, folate, and betaine. These supplements can help support the metabolism of homocysteine and prevent its accumulation in the blood. However, it is important to consult with a healthcare professional before starting any supplements, as the dosage and appropriateness may vary for each individual. Read the full article

0 notes

singleroad · 1 year ago

Text

I did 23andMe 4yrs ago and uploaded by DNA sequence to Promethease for fun but looked at it again this weekend and realized that I have that MTHFR gene mutation

but

I don’t have the big one that is known to cause miscarriages and birth defects etc… but it is one known to cause issues with folate metabolism

I also have problems with DCA absorption, so… that gene says less meat, MTHFR says I shouldn’t be vegetarian lmao

I need to do more research

Trying to find a folate vitamin that my body can absorb

This comes from trying to do research on what supplements I should take to increase fertility and ovum health (and lessen endometriosis symptoms)

looking at folate, CoQ10, inositol, magnesium, selenium, fish oil, vitamin D, calcium, NAC, B12, EGCG

I want to try vitamin E as well but need to be sure it is in it’s pure form bc otherwise it risks concealing the early signs of cancer like melanoma 🤔

1 note · View note

tohealthwiththatmthfr · 1 year ago

Text

MTHFR: The Gene That Can Affect Your Health and How to Optimize It

The MTHFR gene is involved in the methylation process, which is essential for many important bodily functions, including DNA repair, detoxification, and the production of neurotransmitters. About 40% of people have a variation in the MTHFR gene that can interfere with its function. This can lead to a number of health problems, including:

Increased risk of chronic diseases, such as heart disease, stroke, and cancer

Mental health problems, such as depression and anxiety

Fertility problems

Fatigue

Headaches

Sleep problems

There are a number of things that people with the MTHFR gene mutation can do to optimize their genes and improve their health. These include:

Eating a healthy diet that is rich in folate, vitamin B12, and choline.

Taking supplements that contain methyl folate and active B12.

Avoiding processed foods, alcohol, and caffeine.

Getting regular exercise.

Managing stress.

If you are concerned that you may have the MTHFR gene mutation, you can talk to your doctor about getting tested. If you do have the mutation, there are a number of things that you can do to improve your health and well-being.

Here are some additional tips for optimizing your genes with MTHFR:

Get enough sleep. Sleep is essential for methylation, so make sure you are getting at least 7-8 hours of sleep per night.

Manage your stress levels. Stress can interfere with methylation, so find healthy ways to manage your stress levels, such as yoga, meditation, or spending time in nature.

Get regular exercise. Exercise helps to improve circulation and detoxification, which can both support methylation.

Avoid toxins. Exposure to toxins can interfere with methylation, so avoid exposure to environmental toxins, such as pesticides, heavy metals, and cigarette smoke.

By following these tips, you can help to optimize your genes with MTHFR and improve your overall health and well-being.

#MTHFR #mthfrwarrior #mthfr gene mutation #mthfrawareness

0 notes

nutritionexpert · 4 years ago

Text

personalized Nutrition

Mariam Ashfaq

Personalized Nutrition:

Personalized nutrition (PN) is also termed “as nutritional genomics and personalized or customized nutrition”. Personalized nutrition directs the consumption of diet for health optimization and wellbeing. Factors: Many factors contribute such as:

Biochemistry

Metabolic rate

Inherited genes

Microbiomes

Physical activity level

Sleep pattern

Dietary habits

Epigenetics

Need of Personalized Nutrition:

As it has been stated according to many researches that chronic diseases are the main leading cause of death in worldwide. Moreover, it has also been deduced that consumption of poor diet sources is a risk factor for chronic diseases.

It has been investigated that the diseases such as obesity, cardiovascular and cancer can originate in the first two years of life due to lack of nutrient rich diet. Thus, PN has been noticed to explicate and positively influence that diet figures an individual’s response to nutrients and, mutually, that genetic composition influences the metabolism of nutrients and requirements of nutrients in regard to optimize the capability and health.

Weight management

Improve mood and productivity

For diabetes

Cancer, cardiovascular and arthritis

For hormone imbalancenment

Individuals with GI complaints

Elements of personalized nutrition:

Personalized nutrition is referred to as the customized nutritional guild lines and interventions to manage, cure and avert the onset of chronic diseases and improve health and quality of life. Three elements defined the basics of personalized nutrition: 1. Personalized sciences and data 2. Personalized guidance and therapeutics 3. Personalized education and training

Relation of omics and personalized nutrition:

Genomics the study of hereditary genes helps to determine the incidence of mutation in genes or provide the knowledge of genetic disorders in order to design more effective nutritional strategies or guidelines to optimize the well-being. Hence, decoding the gene expression can help to diagnose the underlying cause of disorders. Therefore, translation of omics data can facilitate to develop clinical and personalized interventions. This may include:

Proteomics: it defines the encoding of protein within the genetic material of human being and characterizing the protein functions.

Metabolomics: it refers to the metabolites produced as a result of protein action.it ensures the level of concentrated metabolites.

Microbiomes: this discipline refers to the gut microbiomes activity within their respective cavities such as oral, vagina or intestinal lumen. The colonization of these microbiomes influences the digestion and absorption of food. They play a role in defining the biological processes and indicate the health issues such as diabetes, inflammation in brain or host immune function modulation. Hence, study of genome and microbiome help to design more personalized nutritional interventions to manage, prevent and cure the disease.

Nutritional genomics:

The branch of nutrition which usually involve:

Nutritional genomic

Nutri-genetics

Epigenetics

Nutritional genomics:

It mainly emphasizes on diet disorders and lifestyle disorders and also defines the interaction between the inherited genes and environmental factors like bioactive components in food, containments, stress and sleep.

Nutri-genetics:

It identifies the variation in genetics which impacts the functioning of organs. For an instance the mutation in gene 5,10-methylenetetrahydrofolate reductase (MTHFR) which is convert folate or folic acid into 5-methyl folate which is the active form of folic acid can result in the low activity of enzymes. Hence, no activation of folic acid therefore, these individuals require active form of folic acid to optimize their health.

Epigenetics:

The field of epigenetics explains that genes which contain all the genetic information responsible for organ functioning as once an organ cell is differentiated and well defined for its functioning are not only the risk factor for the onset of chronic diseases. However, the environmental element or lifestyle factor also play a role along with genes as for an instance it is not uncommon for two identical twins having the same genetic makeup and characteristics that one of them can suffer from disease however other may be healthy. Therefore, it is concluded that not only genetic expression is a culprit for a disease but lifestyle can be too.

Genetics and Nutrition Therapy:

The gene expression can be controlled at two levels mainly referred as:

Genomic

Epigenomics

Transcription of DNA occur by several transcription factors in which ligand and specialized proteins, RNA polymerase attaches to promoter and initiate the process of transcription.it has been deduced that any ligand or any mutation can initiate or inhibit the process of transcription. Hence, bioactive components of food such as omega-3 or omega-6, curcumin, resveratrol, genistein or quercetin can act as a ligand and can activate the process of transcription in a well-defined manner.

However, some pro-inflammatory gens can inhibit the process therefore, it is concluded that these bioactive components of foods can inhibit proinflammatory transcription such as interleukin -1 or nuclear factor kappa B, which in return reduces the chance of genetic mutation or cancer.

Another marker, epigenetic control can be done at two level, histone modification or DNA modification.it has been deduced that epigenetics only influence during fetal stage in which DNA is modified.

But now recent research concluded that epigenetics greatly influences the adulthood as in this phase alteration in DNA methylation has been seen. Hence, epigenetic is also associated with several chronic diseases such as cancer and diabetes. Therefore, environmental factor and diet also contribute.

Allergen free diet:

Every human body immune system responds differently for an instance, some people may have severe allergic reactions called as anaphylaxis due to some food allergen and symptoms may include:

Shortness of breath

Redness

Swelling

Sneezing

Rhinitis

Ulceration

Dermatitis

Skin reactions

Itching

Wheezing

coughing

Practitioners recommend allergen free diet to those individuals who show Ig E mediated response to some food allergens. Such diet includes peanut free die, tree nut free diet, gluten free diet, casein free milk or yogurt or low FODMAP. Glycemic response:

Personalized nutrition is important in case of diabetes myelitis as according to a research seen in individuals suffering from diabetes different post prandial glycemic response was observed when given same meals. Therefore, it was decided that personalized diet should be prescribed which depend upon physical activity, sleep, dietary pattern and stress. Hence, personalized nutrition helps to control glycemic ratio and prevent hyperglycemia which when progress for long-term can cause kidney failure or cardiovascular disease.

For an instance in a research it was investigated that one group consisting of 20 healthy males and the other group consisting of 20 males suffering from diabetes type 2 where tested by giving them glucose drink. The result suggested that there was difference in two group due to different metabolic response

Another study in which individuals were given two kinds of bread some show high glycemic index to one bread and some show low glycemic index.

Ketogenic diet:

Ketogenic diet, termed as high protein diet and low carbohydrate and low-fat diet is usually prescribed to drive body’s metabolic system in the ketosis state.

This type of diet usually prescribed to patients such as diabetes. Cardiovascular diseases respiratory disease, females suffering from polycystic ovary syndrome and cancer. latest research also suggests this diet for weight loss as ketones play a role as fuel for body cells.

Nutrition in different stages of life:

Types of nutrients and food choices and calories differ in different stage of life such as in pregnancy there is more need of calories, iron, calcium and protein. However, in older age fewer calories are required but more nutrient dense food is recommended

Nutrition in different diseases:

Type of nutrient vary in different disorder or diseases for an instance

In kidney failure low phosphate and low protein diet is recommended

In cardiovascular diseases low sodium and triglyceride diet is given

In diabetes low glycemic index food is recommended however, this diet vary from person to person due to other factors

Microbiota level

Sleep pattern

Physical activity

Genetics

Stress level

Age factor

Food preferences

Psychology

Personalized nutrition for weight loss:

In research conducted in UK on obese individuals. Seventy-five individuals were divided into three sections and different eating pattern were implemented on them.

One of these sections, individuals who found difficult to stop eating due to lack of sensation of feeling of fullness which usually result from the hormone dysfunction, were recommended to consume high protein rich diet and low carbohydrate diet to help them feel satiety.

In other group fasting technique was applied in 5:2 days.in this technique people having the genes which prevent the brain to send satiety signals were recommended to have 12 to 16-hour gap between meals to reduce the consumption of calories. it was done in such such am way that two days fasting and eating normally for five days.

Last group, emotional eaters were treated through cognitive and psychological therapy to overcome the habit of emotional eating and in return decreasing weight.

It was concluded that individual who consume more protein and less carbohydrate lose 8%of their body mass. therefore, metabolic rate differs from person to person hence, personalized diet is recommended.

Benefits:

Long term weight loss

It slow down aging process

It improves mood and increase productivity

It enhances fertility rate

Reduce chronic diseases such as diabetes, cancer and cardiovascular

Reduce pain and stiffness in arthritis

Challenges of personalized nutrition: 1. Nutrition research: The main challenge faced by many practitioners are as the translated data of human genome is unable to implement as clinical intervention. As the data collection can be costly, may require technicians to operate devices and DNA testing equipment’s which are not affordable for everyone. However, there are many apps for identifying the parameters of health but they are not likely to produce accurate results. Therefore, there is a need for policy making to initiate the platform for public health and well being by installing the technologies and devices or artificial intelligence. 2. Practitioners: Many researchers concluded that many practitioners faced problems in providing personalized strategies according to omics data. 3. Professional education: For an education and training of public, the personalized nutrition should be included in the curriculum of students. institutions should develop policy to educate individual and aware them about recent research of health care. Conclusion: Personalized nutrition is a field that can help humans to prevent, manage and cure the disease.as it includes the translation of human genome and phenotype therefore, is more accurate and can suggest more effective strategies to prevent the onset of disease. However, challenges faced by practitioners can be overcome by developing policies for health care and by providing nutrition education to the public.

#Marriam Ashfaq

2 notes · View notes

healthysimplified-brittneyn · 5 years ago

Text

IdLife DNA Spotlight !!

Melanie’s business Real Strong Mom is all about “real food • real fitness • real life” and for Melanie it didn’t get anymore real than what she discovered from her DNA test!

Even as a successful health and fitness coach, Melanie has faced her own health struggles; lack of energy, drive and even trouble losing fat. Instead of spinning her wheels on things that “might work” she decided to find out what her body actually needed. Here’s what her DNA test revealed:

1. She carries the double mutation for MTHFR gene which results in reduced levels 📉 of activated folate and consequently, elevated 📈homocysteine levels. Folate is essential for brain 🧠 development and nerve function. In order to mitigate the risks associated with this gene variant we have removed folic acid (synthetic) and pumped in lots of folate rich foods like lentils, spinach, broccoli 🥦 and black beans.

2. Melanie has slightly reduced levels of vitamin D and increased requirements of B6. The lack of these two vitamins are most likely contributing to her lack of energy and drive. By adding in foods rich with these vitamins like eggs 🥚, tuna, avocado 🥑 and spinach as well as getting sun ☀️ exposure for at least 30 minutes a day. These adjustments have resulted in huge difference in energy and drive.

3. With one functional copy of the ACTN3 gene she is built for both sprint and endurance activities. This was confirmation that adding in explosive movements like jumping rope or sprints to her heavy lifting is just what her body needed!

4. A medium sensitivity to fats means she needs to pay attention to her proper ratios of different types of dietary fats. So yes she can keep the peanut butter 🥜 (she’s Loves peanut butter) but she’s also added in some other goodies like olive oil and avocado 🥑.

5. She has a low sensitivity to caffeine ☕️....phew! Melanie was super nervous the test was going to reveal her body didn’t respond well to caffeine. With a low sensitivity she can consume up to 400 mg (4 cups) without it bothering her.

Melanie was blown away with the information provided in her DNA test. She has been able to make changes to her nutrition, lifestyle and training that has improved both her energy and drive but also has helped her shed those last few pounds!

#DNA

#IDNUTRITION

2 notes · View notes

pineapplecoreconfidentials · 5 years ago

Text

🍍

Transfer questions for your doc

So, with only two little blast embabes making it to the genetic testing phase this round, and only one (which was determined abnormal) last round, I’ll suffice it to say that it is not in the cards for me to have a plentiful bounty of embryos chillin (literally) in storage, waiting to be plucked out and implanted in my uterus. I will not have the luxury of over abundance, or even abundance. With scarcity comes planning, or over planning.

So if (WHEN) we step up to the transfer phase of IVF, you best believe I’ll be having a sit down with my doc to make sure conditions are as favorable as freakin possible. Nothing that can be left to chance will be left to chance.

Yes, I’m a bit much. I’m not a big believer in that go-w-the-flow business when the tank is nearing E; that’s how you get stuck in the middle of nowhere, Jan (insert: eye roll).

A fellow IVF online warrior qween posted a list of questions she’s compiled to ask prior to a higher-risk transfer (cough, cough). Posting the list so that 1). it doesn’t need to sit in an unopened email in my inbox for the next x cycles, staring at me and haunting me, and 2). ya’ll can hopefully benefit.

Questions:

Is my uterine environment favorable for a transfer aka any concerns for:

endometriosis (receptiva test)

endometritis (biopsy/scratch)

polyps, fibroids, or other anomalies (hysterscopy, saline sono, HSG to check for hydrosalpinx)

Is the transfer at the right time (aka should I have an ERA procedure)?

Should a natural cycle FET be considered? If not, why?

Are there any lining concerns?

Are my hormones (estrogen and progesterone) where they should be in cycle, after retrieval, now?

Would a recurrent loss panel provide any useful information, if I haven’t suffered a loss?

Are there concerns about a clotting disorder and/or MTHFR (aka would baby aspirin be a good addition)?

(If there are any autoimmune issues to consider) would adding prednisone, medrol or Benadryl be advised? Should I consult a reproductive endocrinologist?

What general health changes should be considered (such as diet, gf/df, work out intensity, acupuncture)?

Printing this baby out and saving her for when (SEE? I’m learning) the level up presents itself.

#ivfjourney #ttc with infertility #ivfwarriorqween #ttc #ivf #transfer cycle #themoreyouknow

3 notes · View notes

moonlightlacrima · 5 years ago

Text

Well it’s seems that my list of diagnoses is getting longer.

Recently I went to my neuro-chiropractor to figure out about some back pain & tingling that I’ve been having. After explaining everything to him, including my symptoms & health history, he told me that he wanted to do blood work & test for a genetic mutation called MTHFR mutation. I said sure why not. So after that appt, I go get an X-ray (for my back pain & tingling) and get blood work. Go back for my next appt. X-ray shows I have scoliosis (mild, but rare to be just diagnosed as an adult) and some disk degeneration. Those we can treat. Then comes the bloodwork. My numbers are all over the place. None of it makes sense together. Not all of the bloodwork has come in yet. Schedule another appt for today. Today we go over all the bloodwork. We go over some of the stuff we went over last time but in more depth. Then we get to the mutation. I do have it. I have it in both alleles. This explains my fatigue. My depression. My pain. Why I feel like shit (besides the fact that I have an autoimmune disorder). He then goes to say, “you’re body is a ticking time bomb. it’s like you have the kerosene, but no match.” and he also says, “when you get serious with someone in the future & want children, they’ll need to be genetically tested.” I could pass this on to my future children. I could cause problems for my future children. I’d be a high risk pregnancy (I knew I might have trouble with pregnancy in the future as I might have antiphospholipid syndrome, but that has been a maybe right now. No definitive diagnosis yet). Thankfully the symptoms can be controlled as long as I take two supplements. We are also changing my diet to help with the other problems that showed up in my bloodwork. And I guess we’ll talk more about the scoliosis next visit.

#ashley’s late night ramblings #shut up ashley #health tag #kinda long post

1 note · View note

bookpiofficial · 3 years ago

Text

Methylenetetrahydrofolate Reductase Gene and Potential Risk to Autism Spectrum Disorder | Chapter 13 | New Horizons in Medicine and Medical Research Vol. 7

The goal of this study was to see if the methylenetetrahydrofolate reductase (MTHFR) variations in the Saudi community altered susceptibility to the risk of autistic spectrum disorder (ASD).

Methods and Subjects: The severity of ASD symptoms was assessed using diagnostic and statistical manual of mental disorders (DSM-V) criteria and scores on the childhood autism rating scale (CARS). TaqManTM genotyping assays for the 677C>T rs1801133 and 1298A>C rs1801131 SNPs in the MTHFR gene were used to assess genomic DNA from buccal cells of 112 patients with ASD and 104 healthy controls. The optimum interactive inheritance method for selected SNPs was determined using the SNPStats software (https://www.snpstats.net). The protein-protein interaction network of the MTFR gene was predicted using the Search Tool for the Retrieval of Interacting Genes (STRING) database (https://string-db.org).

Controls in the studied SNPs were compatible with Hardy-Weinberg equilibrium. The MTHFR rs1801133 C>T and MTHFR rs1801131 A>C SNPs were shown to have associated with ASD risk (odds ratio [OR]= 5.2 and 22.2, respectively). In cases vs controls, genotype relationships of these SNPs were statistically significant (P= 0.0012 and P= 0.0008, respectively). The SNPs studied were shown to be strongly linked to ASD cases with a score of 37 (codominant and recessive models; P= 0.001 and P= 0.0005, respectively). The C/C-A/A genotype was the most prevalent among six combination genotypes in ASD cases (42.9 percent ). A substantial variation in haplotype distribution between patients and controls was found in a global haplotype analysis (P=0.00057). The two SNPs were discovered to be in linkage disequilibrium (D'= 0.63, r2 = 0.260).

Conclusion: The MTHFR rs1801133 and rs1801131 SNPs interact to increase the risk of ASD, particularly when verified in larger cohorts with other genetic/environmental factors. Our findings could be used to support future genetic association research in the Saudi population, as well as government and health-care professionals working on regional health-management efforts.

Author(S) Details

Nasser A. Elhawary

Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, P.O. Box 57543, Saudi Arabia.

View Book:-

https://stm.bookpi.org/NHMMR-V7/article/view/6671

#Autism spectrum disorder #CARS scores #single nucleotide polymorphism #TaqMan genotyping #linkage disequilibrium #combined genotypes

0 notes

gopali · 3 years ago

Text

WEEK 1 ASSIGNMENT

DATA ANALYSIS (WEEK-1)

I chose Gapminder dataset for my analysis as I am interested in understanding the various social or economic issues of humankind and in trying to establish their causes and influences. Gapminder is a non-profit venture that seeks to promote sustainable global development and achievement of the United Nations Millennium Development Goals. Its purpose is to increase the use and understanding of statistics about social, economic, and environmental development at local, national, and global levels.

VARIABLES NAMES

alcconsumption

breastcancerper100TH

Research question: Is Alcohol consumption affects Breast Cancer? Literature Review

The objective of this study was to outline the biological pathways of alcohol-attributable breast cancer, the epidemiological risk relationship between alcohol consumption and breast cancer, and the global burden of breast cancer incidence and mortality attributable to alcohol consumption, with a focus on light drinking. First, the literature regarding the biological mechanisms of how alcohol affects the risk of breast cancer was reviewed and summarized. Second, a search of meta-analyses that evaluated the risk relationship between alcohol consumption and breast cancer was conducted. Last, the burden of alcohol-attributable breast cancer incidence and mortality was estimated by means of a Population-Attributable Fraction methodology. Data on alcohol consumption were obtained from the Global Information System on Alcohol and Health, and data on cancer incidence and mortality were obtained from the GLOBOCAN database. Alcohol consumption affects breast cancer risk through the alteration in hormone levels and the associated biological pathways, the metabolism of ethanol resulting in carcinogens, and the inhibition of the one carbon metabolism pathway. The systematic review found 15 meta-analyses on the risk relationship between alcohol consumption (also light consumption) and the risk of breast cancer. All but 2 of these analyses showed a dose-response relationship between alcohol consumption and the risk of breast cancer. An estimated 144,000 (95% confidence interval [CI]: 88,000 to 200,000) breast cancer cases and 38,000 (95% CI: 2,400 to 53,000) breast cancer deaths globally in 2012 were attributable to alcohol, with 18.8% of these cases and 17.5% of these deaths affecting women who were light alcohol consumers. All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption. Due to this strong relationship, and to the amount of alcohol consumed globally, the incidence of and mortality from alcohol-attributable breast cancer is large.

Conclusion

Recent publications add to the current body of evidence that consumption of alcoholic beverages is causally associated to cancer of the female breast, even at low levels of alcohol consumption.

Current data indicate that breast cancer risk does not vary by beverage type and strengthen the evidence that ethanol is the main causal factor; nevertheless, other compounds present in various alcoholic beverages may play a role in, or prevent, the development of breast cancer. Polymorphisms in genes involved in the formation and detoxification of ethanol metabolites are known to modulate the risk of cancer at other sites, and could modulate the association of alcohol consumption with breast cancer risk; however, at present, results are controversial and do not allow the identification of susceptibility alleles for breast cancer subtypes. Experimental and epidemiologic studies show that alcohol-induced breast cancer may be related to an enhanced responsiveness to ER, thus suggesting that the association may be stronger for exposure during adolescence and early adulthood. In addition, there is growing evidence of an environmental impact on the breast cancer epigenome through nutrition. The MTHFR polymorphism appears to play a role via a folate-dependent epigenetic mechanism also modified by ethanol and possibly by menopausal status. However, the precise targets of epigenetic deregulation in breast cancer are still unclear; the field is rapidly expanding and additional data may allow the identification of specific methylation signatures. REFERENCES: https://pubmed.ncbi.nlm.nih.gov/27130687/

https://www.sciencedirect.com/science/article/pii/S0749379713006466

0 notes

your-dietician · 3 years ago

Text

LRP5 and MTHFR gene variants with osteoarthritis prevalence

New Post has been published on https://depression-md.com/lrp5-and-mthfr-gene-variants-with-osteoarthritis-prevalence/

LRP5 and MTHFR gene variants with osteoarthritis prevalence

Masaki Nakano,1,&ast; Haruka Yui,1,&ast; Shingo Kikugawa,2 Ryosuke Tokida,3 Noriko Sakai,4 Naoki Kondo,5 Naoto Endo,5 Hirotaka Haro,6 Hiroki Shimodaira,1 Takako Suzuki,1,7 Hiroyuki Kato,1 Jun Takahashi,1 Yukio Nakamura1

1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan; 2DNA Chip Research Inc., Minato-ku, Tokyo, 105-0022, Japan; 3Rehabilitation Center, Shinshu University Hospital, Matsumoto, Nagano, 390-8621, Japan; 4Department of Orthopaedic Surgery, New Life Hospital, Obuse, Nagano, 381-0295, Japan; 5Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, 951-8510, Japan; 6Department of Orthopaedic Surgery, University of Yamanashi Graduate School of Medicine, Chuo, Yamanashi, 409-3898, Japan; 7Department of Human Nutrition, Faculty of Human Nutrition, Tokyo Kasei Gakuin University, Chiyoda-ku, Tokyo, 102-8341, Japan

Correspondence: Yukio Nakamura Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan Tel +81-263-37-2659 Fax +81-263-35-8844 Email [email protected]

Objective: Osteoarthritis (OA) is a common and degenerative joint disorder in the elderly. A greater importance of understanding the relationship between genetic factors and OA prevalence has emerged with population aging. We therefore investigated the associations of several bone disease-related genetic variants with the prevalence of OA and osteoporosis in Japanese elderly women from the Obuse study cohort, which was randomly sampled from a basic town resident registry. Methods and Results: In total, 206 female participants (mean ± standard deviation age: 69.7 ± 11.0 years) who completed OA, bone mineral density, and genotype assessments were included. The number of patients diagnosed as having knee/hip OA and osteoporosis was 59 (28.6%) and 30 (14.6%), respectively. Fisher’s exact testing revealed significant relationships between the minor T allele of LDL receptor related protein 5 (LRP5) rs3736228 and the prevalence of knee/hip OA and osteoporosis. The respective odds ratios (ORs) of the TT genotype for knee/hip OA and osteoporosis were 7.28 (95% confidence interval [CI] 2.22– 28.08) and 5.24 (95% CI 0.95– 26.98). An additional subgroup analysis for knee OA revealed that the frequency of the common C allele of methylenetetrahydrofolate reductase (MTHFR) rs1801133 had a statistically significant protective association with the prevalence of knee OA (OR 0.58, 95% CI 0.35– 0.97). Conclusion: In sum, the present study demonstrated significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women. These results will help further the understanding of OA pathogenesis and related genetic risk factors.

Introduction

Osteoarthritis (OA) is a common degenerative joint disorder occurring with age whose pathophysiology remains incompletely understood. At present, almost all non-surgical treatment options for OA are limited to analgesis and improving joint movement, with no fundamental cures.1 Osteoporosis is a widespread metabolic skeletal disease characterized by diminished bone mineral density (BMD) or bone strength, both of which increase the risk of fractures. Although several effective medications exist,2 both osteoporosis and OA are becoming major worldwide health concerns with population aging and rising health-care costs. Therefore, understanding the genetic risk factors for these disorders has emerged as an important issue for disease prevention and therapeutic management.

Many studies on the association of genetic factors with OA and osteoporosis have been reported to date. In the present day, the relationships among genetic variants and related disorders are generally investigated by genome-wide association studies (GWAS). Regarding the prevalence of OA and osteoporosis, 256 and 22 records, respectively, were found in the GWAS catalog (https://www.ebi.ac.uk/gwas/).3 Several gene polymorphisms appear to affect OA as well as osteoporosis. Indeed, associations of gene variants in LDL receptor related protein 5 (LRP5),4,5growth differentiation factor 5 (GDF5),6,7 and SMAD family member 3 (SMAD3)8,9 with OA prevalence have been reported. In addition, we very recently uncovered a novel association between a homocysteine metabolism-related methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133), which was reportedly related to osteoporosis, and the progression of spinal OA.10

We have recently established a new population-based epidemiological study of Japanese people that employs random sampling from the basic resident registry of Obuse, a rural town in Japan.11,12 The Obuse study contains detailed medical information on the community-dwelling elderly population with minimized selection bias, which allows for examination of a cohort representative of the general population. The present study aimed to investigate the associations of several reported bone disease-related genetic variants, including MTHFR rs1801133, with the prevalence of OA and osteoporosis in elderly women sampled from the Obuse study cohort. Significant associations were seen for LRP5 rs3736228 with the prevalence of knee/hip OA and osteoporosis, and for MTHFR rs1801133 with knee OA prevalence in Japanese elderly women.

Methods

The study protocol of this investigation for human research was approved by the investigational ethics review board of Shinshu University Hospital, Japan (approval number: 2792). The research procedure was carried out in accordance with the ethical guidelines of the 2013 Declaration of Helsinki. Written informed consent for research and publication was provided by all participants prior to the initiation of the study.

Study Subjects

The Obuse study was launched in October 2014 for epidemiological data collection until June 2017. The study randomly sampled 1297 male and female individuals from 5352 members of the resident population between 50–89 years of age in the basic resident registry of Obuse town (Nagano Prefecture, Japan) as a joint collaboration with the cooperating town office. In total, 203 male and 212 female participants provided written informed consent and were enrolled in the Obuse study. The current investigation included 206 female subjects who completed assessments of knee and hip OA, BMD measurements of the total hips and lumbar spine, and genotype determination of the gene variants of interest. Due to budget constraints, we analyzed only female subjects who were susceptible to systemic skeletal disorders including OA and osteoporosis compared to males.

Assessment of OA and Osteoporosis

OA of the knee and hip was assessed by radiographic examination. The degree of degeneration was evaluated in accordance with the Kellgren–Lawrence (KL) grading system.13 Radiographs were examined by 2 experienced orthopaedic surgeons (H.S. and Y.N.). The subjects with the worst KL grading of ≥ 3 in either side of the knees or hips, or who had undergone arthroplasty for OA were judged as OA patients. The subjects with persistent joint pain and tenderness were also radiologically assessed as having OA. BMD at the lumbar spine and hips was measured using dual-energy X-ray absorptiometry (DXA; PRODIGY, GE Healthcare, Chicago, IL). The regions of interest for lumbar and hip BMD were the L2–4 spinal and bilateral total hip regions, respectively. Subjects with BMD values of ≤ 70% of the young adult mean (YAM) for either the lumbar region or total hips were diagnosed as having osteoporosis.14

Determination of Genetic Variants

Cell-free DNA (cfDNA) was extracted from plasma samples of study subjects using a QIAamp Circulating Nucleic Acid Kit (Qiagen, Venlo, Netherlands) according to the manufacturer’s instructions. Genotyping assays were performed by a droplet digital polymerase chain reaction (ddPCR) QX200 system (Bio-Rad, Hercules, CA). Reaction mixture aliquots of 20 µL containing 10 µL 2 × ddPCR Supermix, 5 µL cfDNA sample, and 0.5 µL 40 × TaqMan SNP Genotyping Assay for each variant (Applied Biosystems, Waltham, MA) were prepared. The droplets were generated with a QX200 droplet generator and carefully transferred to 96-well PCR plates. After PCR cycling (40 cycles of 94°C for 30 s and 60°C for 1 min), the fluorescence of each droplet was determined using a QX200 droplet reader followed by analysis with QuantaSoft version 1.7.4 software (Bio-Rad). The present study examined the following genetic variants: LRP5 rs312009 and rs3736228, GDF5 rs143383, SMAD3 rs12901499, and MTHFR rs1801133.

Statistical Analysis

The background characteristic data of each study group (healthy control, OA, osteoporosis, and comorbid with OA and osteoporosis) are presented as the mean ± standard deviation (SD) together with the median value. Fisher’s exact test was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) of variant genotypes and alleles for the prevalence of OA and osteoporosis versus healthy controls. To examine the population homogeneity of the study participants, Haldane’s exact test for Hardy–Weinberg equilibrium (HWE) was calculated. All statistical tests were carried out by using R version 3.4 software.15 A two-tailed P-value of < 0.05 was considered statistically significant in this study.

Results

Background Characteristics of Study Subjects

The average ± SD age of the 206 female subjects at enrollment was 69.7 ± 11.0 years. The number of patients diagnosed as having OA and osteoporosis was 51 (24.8%; knee: 40, hip: 3, knee and hip: 8) and 22 (10.7%), respectively. Eight patients (3.9%) suffered from both osteoporosis and OA (knee: 6, hip: 1, knee and hip: 1) and were classified into the comorbid group. One hundred and twenty-five subjects having neither OA nor osteoporosis were defined as healthy controls in this study. The background characteristics of the study groups are summarized in Table 1.

Table 1 Background Characteristics of the Study Groups

Associations of Genotype and Allele Frequencies with OA and Osteoporosis

In the present cohort, we observed no remarkable associations for LRP5 rs312009, GDF5 rs143383, or SMAD3 rs12901499 with both OA and osteoporosis prevalence (Tables 2 and 3 and Figures 1 and 2). In contrast, the minor T allele of LRP5 rs3736228 and its homozygotic genotype showed significant relationships with the prevalence rate of knee/hip OA. The ORs of the TT genotype and T allele for OA compared with healthy controls were 7.28 (95% CI 2.22–28.08; P < 0.001) and 1.80 (95% CI 1.07–3.00; P < 0.05), respectively (Table 2 and Figure 1). Although not significantly, the common C allele of MTHFR rs1801133 tended to protect against knee/hip OA prevalence. The respective ORs of the CC genotype and C allele for OA were 0.55 (95% CI 0.23–1.22; P = 0.15) and 0.70 (95% CI 0.43–1.14; P = 0.13) versus the healthy control group (Table 2 and Figure 1). The prevalence rate of osteoporosis was significantly correlated with the TT genotype of LRP5 rs3736228 (OR 5.24, 95% CI 0.95–26.98; P < 0.05) (Table 3 and Figure 2). The distributions of genotype frequencies were in Hardy–Weinberg equilibrium (HWE P-value > 0.05).

Table 2 Genotype and Allele Frequencies in Patients with Osteoarthritis

Table 3 Genotype and Allele Frequencies in Patients with Osteoporosis

Figure 1 Odds ratios for osteoarthritis by each variant genotype. Fisher’s exact test was employed to calculate the odds ratio and 95% confidence interval of variant genotypes for the prevalence of osteoarthritis versus the healthy control group.

Abbreviations: LRP5, LDL receptor related protein 5; GDF5, growth differentiation factor 5; SMAD3, SMAD family member 3; MTHFR, methylenetetrahydrofolate reductase.

Figure 2 Odds ratios for osteoporosis by each variant genotype. Fisher’s exact test was employed to calculate the odds ratio and 95% confidence interval of variant genotypes for the prevalence of osteoporosis versus the healthy control group.

Abbreviations: LRP5, LDL receptor related protein 5; GDF5, growth differentiation factor 5; SMAD3, SMAD family member 3; MTHFR, methylenetetrahydrofolate reductase.

Subgroup Analysis for Knee OA Prevalence

In a subgroup analysis, we focused on the prevalence of knee OA, which was the most common disorder witnessed in this study. In knee OA only or knee OA + comorbid osteoporosis patients, both the TT genotype (P < 0.001) and T allele (P < 0.05) of LRP5 rs3736228 associated significantly with knee OA prevalence as compared with healthy controls (Table 4). Moreover, the C allele of MTHFR rs1801133 demonstrated a statistically significant protective association with the prevalence rate of knee OA (OR 0.58, 95% CI 0.35–0.97; P < 0.05) in the knee OA + comorbid osteoporosis subgroup (Table 4).

Table 4 Subgroup Analysis of Patients with Knee Osteoarthritis

Discussion

This study demonstrated a significant relationship between LRP5 rs3736228 and the skeletal disorders of OA and osteoporosis in elderly community-dwelling female residents randomly sampled from a Japanese town resident registry. A statistically significant protective association of the common allele of MTHFR rs1801133 with knee OA prevalence was also observed. As the population sampling of our cohort minimized selection bias, our results might be considered reflective of the Japanese general population.

LRP5 and 6 (LRP5/6) are required as co-receptors for canonical Wnt signaling16,17 and play important roles in skeletal development and metabolism. A number of LRP5 gene variants have been reported. Of those, associations of the missense variants LRP5 rs3736228 (Ala1330Val) and rs4988321 (Val667Met) with decreased BMD and the risk of osteoporotic fracture are well described.18,19 In particular, a relationship between LRP5 A1330V and diminished BMD has been identified in the Japanese population as well.20,21 A loss of function in LRP5 increased cartilage degradation in a mouse model22 and was also suggested to be associated with OA. However, little is known on the precise connection between OA and LRP5 gene variants. Although associations of LRP5 rs41494349 (Gln89Arg) with spinal OA4 and LRP5 rs3736228 with knee OA5 have been reported, no information has been recorded in the GWAS catalog to date (https://www.ebi.ac.uk/gwas/).3 Therefore, the findings of this study demonstrating a relationship between the T allele of LRP5 rs3736228 and knee/hip OA prevalence in a randomly sampled population cohort will be of value for further understanding the relationship between OA development and the pathophysiological role of LRP5 dysfunction.

In the subgroup analysis for knee OA, there was a protective association for the common C allele of MTHFR rs1801133 (Ala222Val) rather than a risk association of the minor T allele with the prevalence rate of knee OA. MTHFR is known to act within the methionine cycle and plays an essential role in homocysteine clearance. A functional deficiency of the MTHFR enzyme leads to mild elevation of circulating homocysteine levels.23 The A222V missense variant is a common mutation in the MTHFR gene that causes dysfunctional enzymatic activity. Notably, the T allele of MTHFR rs1801133 has been implicated in decreased BMD and the occurrence of osteoporotic fractures,24,25 and we very recently uncovered a relationship among homocysteine, MTHFR rs1801133, and spinal OA in Japanese postmenopausal women.10 The results of the present study imply a correlation between diminished homocysteine levels and a lowered risk of knee OA prevalence. Since circulating homocysteine levels can be decreased by vitamin B group supplementation,26 the significance of B-vitamins intervention in individuals bearing the T allele of MTHFR rs1801133 for preventing OA development may warrant further investigation.

An intron variant of LRP5 gene rs312009 as well as GDF5 rs143383 and SMAD3 rs12901499 showed no remarkable correlations with OA or osteoporosis prevalence in this study. The rs143383 is located in the 5′-untranslated region core promotor of GDF5, which encodes a chondrogenic protein. A relationship of rs143383 with OA has been demonstrated in various racial groups, including a Japanese cohort.6,7 On the other hand, SMAD3 is a member of the SMAD family of proteins and plays an essential role in mediating the transforming growth factor-beta signaling pathway. A genetic variant, rs12901499, within the intron 1 of SMAD3 is reportedly associated with OA in Caucasian and Asian populations.8,9 However, other studies have shown no relationship for either GDF5 rs143383 or SMAD3 rs12901499 with OA prevalence.27,28 Relatively small number of samples limited to female subjects is a limitation of the current study. Besides, although the subjects were randomly sampled from a resident registry, there was a potential for selection bias due to the low participation rate (32.0%) as a result of the noncompulsory survey design. Furthermore, since it sampled from a single town in Japan, this study might contain local features that should be considered when interpreting the data. Future studies with larger sample size and male subjects that include multiple regions in Japan and/or other Asian countries will overcome the controversial issues. Further investigations including experimental study on the mechanisms and/or pathways will be required as well.

Conclusion

We observed significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women from the randomly sampled Obuse study cohort. The results of the present study will help further the understanding of OA pathogenesis and related genetic risk factors, which will contribute to improved disease prevention and therapeutic management.

Acknowledgments

This work was supported by a grant from the JOA-Subsidized Science Project Research 2018–2020 to Y.N. We would like to thank Dr. Takashi Igarashi of the Center for Clinical Research at Shinshu University Hospital, Dr. Hironobu Sato of the Obuse Town Institute for Community Health Promotion, and the Obuse Town Office for sample selection in this study. Our gratitude extends to Mr. Trevor Ralph for English language editing as well as all participants in the present study.

Disclosure

All of the authors have declared that there were no conflicts of interest in this study.

References

1. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745–1759. doi:10.1016/S0140-6736(19)30417-9

2. Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med. 2017;167(3):ITC17–ITC32. doi:10.7326/AITC201708010

3. Welter D, MacArthur J, Morales J, et al. The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 2014;42(Database issue):D1001–D1006. doi:10.1093/nar/gkt1229

4. Urano T, Shiraki M, Narusawa K, et al. Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women. Spine. 2007;32:25–29. doi:10.1097/01.brs.0000251003.62212.5b

5. Yerges-Armstrong LM, Yau MS, Liu Y, et al. Association analysis of BMD-associated SNPs with knee osteoarthritis. J Bone Miner Res. 2014;29(6):1373–1379. doi:10.1002/jbmr.2160

6. Miyamoto Y, Mabuchi A, Shi D, et al. A functional polymorphism in the 5’ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007;39(4):529–533. doi:10.1038/2005

7. Chapman K, Takahashi A, Meulenbelt I, et al. A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5’ UTR of GDF5 with osteoarthritis susceptibility. Hum Mol Genet. 2008;17(10):1497–1504. doi:10.1093/hmg/ddn038

8. Valdes AM, Spector TD, Tamm A, et al. Genetic variation in the SMAD3 gene is associated with hip and knee osteoarthritis. Arthritis Rheum. 2010;62(8):2347–2352. doi:10.1002/art.27530

9. Yang HY, Hu WH, Jiang T, Zhao H. SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis. Biosci Rep. 2018;38(3):BSR20180380. doi:10.1042/BSR20180380

10. Nakano M, Nakamura Y, Urano T, et al. Associations of homocysteine metabolism with the risk of spinal osteoarthritis progression in postmenopausal women. J Clin Endocrinol Metab. 2021;dgab591. doi:10.1210/clinem/dgab591

11. Uehara M, Takahashi J, Ikegami S, et al. Sagittal spinal alignment deviation in the general elderly population: a Japanese cohort survey randomly sampled from a basic resident registry. Spine J. 2019;19(2):349–356. doi:10.1016/j.spinee.2018.06.346

12. Tokida R, Ikegami S, Takahashi J, et al. Association between musculoskeletal function deterioration and locomotive syndrome in the general elderly population: a Japanese cohort survey randomly sampled from a basic resident registry. BMC Musculoskelet Disord. 2020;21(1):431. doi:10.1186/s12891-020-03469-x

13. Ball J, Jeffrey MR, Kellgren JH, Editors. The Epidemiology of Chronic Rheumatism: Atlas of Standard Radiographs of Arthritis. Oxford, UK: Blackwell Scientific Publications; 1963.

14. Soen S, Fukunaga M, Sugimoto T, et al. Japanese society for bone and mineral research and japan osteoporosis society joint review committee for the revision of the diagnostic criteria for primary osteoporosis. Diagnostic criteria for primary osteoporosis: year 2012 revision. J Bone Miner Metab. 2013;31(3):247–257. doi:10.1007/s00774-013-0447-8

15. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2017. Available from: https://www.r-project.org/. Accessed September21, 2021.

16. Tamai K, Semenov M, Kato Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407(6803):530–535. doi:10.1038/35035117

17. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 2000;407(6803):535–538. doi:10.1038/35035124

18. van Meurs JB, Trikalinos TA, Ralston SH, et al; GENOMOS Study. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA. 2008;299(11):1277–1290. doi:10.1001/jama.299.11.1277

19. Richards JB, Rivadeneira F, Inouye M, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet. 2008;371(9623):1505–1512. doi:10.1016/S0140-6736(08)60599-1

20. Ezura Y, Nakajima T, Urano T, et al. Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone. 2007;40(4):997–1005. doi:10.1016/j.bone.2005.06.025

21. Urano T, Shiraki M, Usui T, Sasaki N, Ouchi Y, Inoue S. A1330V variant of the low-density lipoprotein receptor-related protein 5 (LRP5) gene decreases Wnt signaling and affects the total body bone mineral density in Japanese women. Endocr J. 2009;56(4):625–631. doi:10.1507/endocrj.K09E-133

22. Lodewyckx L, Luyten FP, Lories RJ. Genetic deletion of low-density lipoprotein receptor-related protein 5 increases cartilage degradation in instability-induced osteoarthritis. Rheumatology. 2012;51(11):1973–1978. doi:10.1093/rheumatology/kes178

23. Moll S, Varga EA. Homocysteine and MTHFR mutations. Circulation. 2015;132(1):e6–e9. doi:10.1161/CIRCULATIONAHA.114.013311

24. Bathum L, von Bornemann Hjelmborg J, Christiansen L, Madsen JS, Skytthe A, Christensen K. Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased risk of fractures: results from a population-based Danish twin study. Osteoporos Int. 2004;15(8):659–664. doi:10.1007/s00198-003-1584-z

25. Shiraki M, Urano T, Kuroda T, et al. The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab. 2008;26(6):595–602. doi:10.1007/s00774-008-0878-9

26. Homocysteine lowering trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ. 1998;316(7135):894–898. doi:10.1136/bmj.316.7135.894

27. Tsezou A, Satra M, Oikonomou P, Bargiotas K, Malizos KN. The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the Greek population. J Orthop Res. 2008;26(1):136–140. doi:10.1002/jor.20464

28. Hong JQ, Wang YX, Li SH, et al. Association between SMAD3 gene polymorphisms and osteoarthritis risk: a systematic review and meta-analysis. J Orthop Surg Res. 2018;13(1):232. doi:10.1186/s13018-018-0939-2

Source link

0 notes

paleorecipecookbook · 6 years ago

Text

Methylation and Autism

Demystifying methylation

The topic of methylation has exploded in popularity in recent years. An increasing number of healthcare practitioners are incorporating methylation assessment into their clinical practice, and the market for direct-to-consumer genetic testing, which allows people to identify genetic variants that may impact methylation, is booming.

Methylation is the process of transferring a single carbon atom and three hydrogen atoms, collectively referred to as a methyl group, from one substance to another in the body. The transfer of methyl groups regulates countless biochemical processes, including cell division, gene expression, DNA and RNA synthesis, development of the nervous system, immune cell differentiation, neurotransmitter synthesis, histamine clearance, and detoxification. To learn more about the ins and outs of methylation, listen to my podcasts Methylation 101, Methylation—What Is It and Why Should You Care? and What Influences Methylation? An Interview with Dr. Ben Lynch.

In autism, genetic variants such as MTHFR may load the gun, but the exposome pulls the trigger. There are many simple yet effective steps we can take to modulate the exposome, optimize methylation, and reduce the risk of autism in our children.

Optimal methylation and its opposite process, demethylation, are central to the maintenance of our physical, mental, and emotional health. Consequently, methylation deficits have many adverse effects on the body. Conditions associated with impaired methylation include fatigue, difficulty losing weight, depression, anxiety, hormone imbalances, poor detox capacity, infertility, and an increased risk of cancer. However, a growing body of research indicates that we should add another item to this list of conditions affected by impaired methylation—autism spectrum disorder.

The link between impaired methylation and autism

There is no arguing that autism is on the rise; the incidence of autism in U.S. children increased by over 100 percent from 2000 to 2010, and a shocking one in 59 children born today will be diagnosed with autism. (1) A growing body of research indicates that methylation influences the development of autism. Variants in the MTHFR gene and the presence of folate receptor autoantibodies are two factors that mediate the relationship between methylation and autism.

The MTHFR gene governs the production of methylenetetrahydrofolate reductase, the rate-limiting enzyme of the biochemical pathway that converts 5,10 methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-MTHF), the active form of folate. 5-MTHF is a compound that participates in methylation. An insufficiency of 5-MTHF impairs methylation and adversely impacts brain function. (2) MTHFR genetic variants, such as the C677T variant, reduce MTHFR enzyme activity and lower the level of 5-MTHF in the body. The frequency of the T allele of the C677T variant, which reduces MTHFR activity, is higher in children with ASD than in non-autistic children; this finding suggests that 5-MTHF insufficiency and altered methylation play a role in autism. (3)

Folate receptor autoantibodies (FRAAs) also influence methylation and ASD. FRAAs bind to folate receptor A (FRA) in the brain, preventing folate from entering the brain. Blocked folate receptors cause cerebral folate deficiency, which impairs methylation and brain function. Autistic children have a high prevalence of FRAA compared to non-autistic children. (4) In children with folate receptor autoantibodies, folate must be delivered to the brain via a route that bypasses the blocked receptor. Folinic acid, a non-methylated form of folate, readily crosses the blood–brain barrier and has been found to improve verbal communication in children with ASD. (5) The research on the relationship between MTHFR variants, folate receptor autoantibodies, and ASD suggests that supplying 5-MTHF and folinic acid may help correct methylation deficits and alleviate symptoms in children on the ASD spectrum.

The exposome and autism

The completion of the Human Genome Project in 2003 ushered in an era of “biological determinism,” the belief that human health and behavior are controlled primarily by our genes. However, relying solely on genes to predict and prevent disease is misguided because our bodies don't have enough genes to support the concept of biological determinism. Scientists now understand that factors that influence gene expression, rather than genes themselves, are responsible for driving disease. The study of the mechanisms that change the way genes are expressed but don't alter the underlying genetic code is called epigenetics. Methylation is just one of many epigenetic mechanisms that influence gene expression.

The sum of environmental exposures to which a person is exposed over the course of his or her lifetime, referred to as the “exposome,” epigenetically influences methylation and gene expression. I previously wrote about the exposome in my article “Why Your Genes Aren’t Your Destiny.” In autism, genetic variants such as MTHFR may load the gun, but the exposome pulls the trigger. (6) Some of the environmental factors that epigenetically influence the development of autism include diet, dysbiosis, maternal infection, and environmental toxins.

Dysbiosis

Fascinating new research indicates that gut bacteria epigenetically modulate gene expression; subsequently, alterations in the gut microbiome may impair methylation. (7) Dysbiosis is a common problem among autistic children that may contribute to methylation deficits. (8) Correcting dysbiosis and restoring a healthy microbiome may help correct underlying methylation issues in children with ASD.

Diet

Methylation is catalyzed by several enzymes that require specific dietary micronutrients, including folate, riboflavin, B6, B12, choline, betaine, zinc, and magnesium. A deficiency of these nutrients impairs methylation. (9) Furthermore, research indicates that a Westernized diet high in refined, processed foods alters methylation in the brain and impairs cognitive function; these findings suggest the existence of an important link between the consumption of a processed, nutrient-depleted diet and autism spectrum disorder. (10)

Infection

Maternal infections increase the risk of autism spectrum disorder by epigenetically altering the expression of genes associated with ASD in the fetal brain. (11, 12) Identifying and treating infections before a woman becomes pregnant may significantly reduce the risk of her child experiencing impaired methylation and ASD.

Environmental toxins: Heavy metals and BPA

The abundance of environmental toxins to which we are exposed daily has a significant impact on methylation and the risk of ASD. In utero exposure to heavy metals alters methylation of genes and is associated with an increased risk of autism. (13) Exposure to BPA, an extremely common environmental toxin found in plastic water bottles and food containers, in the lining of canned foods, and on thermal paper used for receipts, also alters DNA methylation and is associated with an increased risk of autism spectrum disorders. (14)

The exposome plays a crucial role in the regulation of methylation and the risk of ASD. Fortunately, there are many simple yet effective steps we can take to modulate the exposome, optimize methylation, and reduce the risk of autism in our children.

Testing and treating methylation problems

Identifying MTHFR genetic variants is a good first step to take when addressing methylation problems in ASD spectrum children. I recommend doing genetic testing through 23andMe. Once you have the results of your child’s 23andMe test, you can run the data through Genetic Genie to get methylation results. Variants in MTHFR C677T increase a child’s risk for methylation issues and autism spectrum disorder.

It is important to remember that just because a genetic variant is present does not mean it is being expressed. I recommend that functional methylation testing, such as the Doctor’s Data or Health Diagnostics Research Institute methylation panel, be done in conjunction with genetic testing. Functional methylation testing can help your healthcare practitioner determine whether a given genetic variant is impacting your child’s health and how to go about treating a methylation deficit. To that end, it is important to work with a practitioner who is familiar with methylation; methylation is a complex topic, and self-treating is often an inefficient (and costly) way to approach this health issue.

It is crucial that epigenetic causes of poor methylation be addressed in children on the ASD spectrum. An ancestral diet provides the nutrients required for methylation, including folate, riboflavin, B6, B12, zinc, choline, glycine, creatine, betaine, and magnesium. Targeted nutrient supplementation can also help; 5-MTHF may benefit autistic children with MTHFR variants and folinic acid helps those with folate receptor autoantibodies. In my practice, I am having success with a methylation protocol developed by Chris Masterjohn that involves choline, glycine, and creatine. You can learn more about Chris’s protocol in his podcasts Living with MTHFR and What to Do about MTHFR.

Correcting dysbiosis with pharmaceutical or botanical antimicrobials, fermented foods, and probiotics can help restore balance to the intestinal microbiota and optimize methylation. Women looking to become pregnant should focus on supporting their immunity to reduce their risk of infection during pregnancy and treat pre-existing infections before becoming pregnant.

Finally, environmental toxins should be avoided as much as possible during pregnancy, infancy, and early childhood to reduce the risk of autism. Some simple ways to minimize toxin exposure include investing in high-quality water filters for drinking and bathing water, using stainless steel and glass water bottles and food storage containers rather than plastic, and avoiding handling receipts. Women planning to become pregnant should assess their body burden of heavy metals and undergo detoxification well before pregnancy to reduce their future children’s exposure to environmental toxins in utero.

Now, I’d love to hear from you. What do you think of the research on methylation and autism? Do you have a child on the ASD spectrum, and if so, what methylation-optimizing strategies have been most helpful? Let me know in the comments below.

The post Methylation and Autism appeared first on Chris Kresser.

Source: http://chriskresser.com July 04, 2018 at 02:49AM

#paleo #recipe #food #delicious #healthy #yum #diet

3 notes · View notes