Definitions, Terms and Abbreviations

Adrenal Fatigue / Failure - is a term applied to a collection of nonspecific symptoms: body aches, fatigue, nervousness, sleep disturbances and digestive problems. The medical term adrenal insufficiency, or Addison's disease, refers to inadequate production of adrenal gland hormones (esp. cortisol and DHEA) as a result of an underlying disease.

Alleles — inheritable sub-parts of chromosomes (1 from each parent)

Allele types and Attributes: Allele types and Attributes

This article "MTHFR C677T and A1298C: Explained In Plain English" attempts to clarify what an MTHFR C677T and A1298C mutation is, in a way you can understand. Another overview "MTHFR A1298C Mutation: Some Information on A1298C MTHFR Mutations" is given by Dr. Ben Lynch. A third is "MTHFR gene variant" from the Genetic and Rare Diseases Information Center (GARD) at the U.S. NIH.

A1298C allele gene mutationA1298C allele gene mutation

C677C allele gene mutationC677C allele gene mutation

Auto-immune disease — occurs when the body produces antibodies that attack its own tissues, leading to the deterioration and in some cases to the destruction of such tissue. Celiac disease is one autoimmune condition, where eating gluten, a protein found in wheat, barley and rye, causes the body to attack the lining of the small intestine. [See: List]

See this grouping of numerous interconnected inflammatory diseases. For more information see: Autoimmune disease and the human metagenome and Inflammatory Disease comes from the Human Microbiome

BH4 Cycle / Tetrahydrobiopterin Cycle — assists with the breakdown of Phenylalanine, cofactor for the formation Neurotransmitters, cofactor to produce Nitric Oxide (NO), assists with the breakdown of Ammonia, a critical cofactor for the rate-limiting enzymes involved in the synthesis of the monoamine neurotransmitters.

Chronic Fatigue Syndrome (CFS) — a group of significantly debilitating medical conditions characterized by persistent fatigue and other specific symptoms that lasts for a minimum of six months in adults (and 3 months in children or adolescents); Also referred to as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or by other terms.

Deoxyribonucleic acid (DNA) — the master nucleic acid carrier of genetic information in the cell capable of self-replication and synthesis of RNA cell-function processors.

Diabetes (Diabetes mellitus / DM) — a metabolic disease in which the body's inability to produce any or enough insulin causes elevated levels of glucose in the blood.

Dopamine — a neurotransmitter, and a precursor of other substances including epinephrine.

Double alleles — two mutated gene sub-parts inherited from one parent, two identical alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.

Epigenetic control — refers to mitotically and/or meiotically heritable variations in gene expression that regulate numerous cellular and biochemical pathways.

Fibromyalgia (FM or FMS) — characterised by chronic widespread pain and allodynia (a heightened and painful response to pressure), with other symptoms include debilitating fatigue, sleep disturbance, and joint stiffness, difficulty with swallowing, bowel and bladder abnormalities, numbness and tingling, and cognitive dysfunction; often associated with depression, anxiety and stress-related disorders.

Folate / Folic Acid (B9, folacin) — one of 8 B vitamins; a key factor in the synthesis (the making) of nucleic acid (DNA and RNA) for cellular replacement and function occurring in green plants, fresh fruit, liver, and yeast. [Deficiency may lead to: loss of appetite, weight loss, weakness, sore tongue, headaches, heart palpitations, irritability, depression and behavioral disorders, and in gestating women leads to birth defects.]

Genes — a unit of heredity that is transferred from a parent to offspring and determines in some measure a characteristic of the offspring.

Gluten — a mixture of proteins, including gliadins and glutelins (present in many types of grains, esp. wheat), that is responsible for the elastic texture of dough. [A mixture of two proteins that causes illness in people with auto-immune disorders, MTHFR gene mutation, celiac disease, etc.]

Hashimoto's thyroiditis — chronic lymphocytic thyroiditis, an autoimmune disease in which the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes. The first disease to be recognized as an autoimmune disease.

Hormones — a regulatory protein chain produced in an organism and transported in the circulatory system or tissue fluids to stimulate specific cells or tissues into action and regulates numerous biochemical pathways and processes.

Homocysteine — an amino acid that occurs in the body as an intermediate in the metabolism of methionine and cysteine. [When elevated it is a marker of a Methyl Cycle abnormality.]

Hyperthroidism — overactivity of the thyroid gland. [Excessive symptoms: resulting in an increased rate of metabolism, increased activity/anxiety or weakness, GI disorders (vomiting and/or loose stools), insomnia, irritability, tachycardia, heat intolerance, increased sweating, hair loss, weight loss, Graves' ophthalmopathy (which causes bulging, reddened eyes, etc.)]

Hypothyroidism — abnormally low activity of the thyroid gland. [Deficiency symptoms: retardation of growth and mental development in children and adults, low metabolism, loss of energy, depression, and with 300+ symptoms.]

Leptin — a peptide hormone protein that plays a key role in regulating energy intake and expenditure, including appetite, produced by fatty tissue and thought to help regulate fat storage in the body.

Lithium — a mineral necessary for enzymes, hormones, vitamins, and growth factors in the body that participates in fertility, glucose useage, mood, mental clarity, etc. [Deficiency symptoms: brittle nails, dry skin, yellowing of teeth, muscle cramps, excessive eye twitching, weakness, and sweating in cold weather. Later stage deficiency symptoms include: muscle spasms, numbness and tingling in the hands, feet, and face, memory loss, depression, hallucinations, poor appetite, and abnormal heart rhythm.]

Lymes disease — infection with unresolved complications from lingering effects of Borrelia burgdorfori (alt sp: burgdorferi; forms endospores/microbial cysts and biofilms) [Bb], Babesia, Bartonella, and Ehrlichia microorganisms. The underlying bacteria take at least three forms: spirochete, microbial cysts, and biofilm.

Magnesium — deficiency causes cramping and pain in a muscle or group of muscles, low bone calcium absorption, increased asthma symptoms, insulin resistance, increased platelet reactivity, increased risk for hypertension, stroke, and other manifestations of atherosclerotic disease, and it affects other body regulatory pathways. See:

Myalgia — pain in a muscle or group of muscles.

Myalgic-encphalomyelitis (ME) [Chronic Fatigue Immune Dysfunction Syndrome (CFIDS), Chronic Fatigue Syndrome)] — a condition causing persistent fatigue that lasts for at least 6 months and isn't due to another medical condition (that is currently known or understood).

Methylation — a complex biochemical process whereby a methyl group is added to the cytosine or adenine DNA nucleotides that are used in the process of making biochemical compounds into usable, re-usable or excretable forms.

MTHFR (Methylenetetrahydrofolate reductase) — rate-limiting enzyme in the methyl cycle.

Multiple Chemical Sensitivity (MCS)- is not a legitimate medical diagnosis, yet! Individuals develop multiple non-specific symptoms by unknown pathways in response to stress after possible exposure to chemical, biologic, or physical agents. [See text: *** MTHFR Resource Center ***]

Neurotransmitters — chemical compounds [Serotonin, Melatonin, Dopamine, Norepinephrine (noradrenaline), Epinephrine (adrenaline)] used at the end of nerve fibers to transmit the nerve signal across synapses; these transfer the impulse to another nerve fiber, a muscle fiber, or some other structure.

Nitric Oxide Cycle (NO) — Nitric oxide is produced by three main enzymes called nitric oxide synthase (NOS). L-arginine, L-Citrulline, Arginine AKG (alpha ketoglutarate) or Arginine Ethyl Ester are semi-essential precursor amino acids for nitric oxide production in the body.

"NOS1 produces nitric oxide that is used in the brain to signal between neurons."

"NOS2 or iNOS, produces inducible NO at a rate 100 — 1000 times normal. NO is poisonous to bacteria and at this high rate of production, the body uses nitric oxide as an important part of the immune system and for wound healing."

"NOS3 or eNOS, is the one that most people think about when we talk about nitric oxide. This enzyme produces nitric oxide in the inner lining of the blood vessels, called the endothelium, which instructs the blood vessels to relax. This relaxing, or expanding of the blood vessels is called vasodilation. Vasodilation helps to reduce blood pressure, improve circulation, and improve waste removal efficiency." Nitric Oxide

Nutrigenomics — the scientific study of the interaction of nutrition and genes, esp. the role of diet in causing disease.

Phenylalanine — is broken down as a cofactor for the formation of Neurotransmitters.

Phosphatidylinositol polyphosphates — regulate diverse functions in the body. Ex: endocrine system regulation.

Pituitary gland — the pituitary produces ACTH to regulate the adrenal gland.

Polycystic ovary syndrome (PCOS) — women with PCOS grow many small cysts on their ovaries. The cysts are not directly harmful but lead to hormone imbalances which contribute to other disease processes.

Probiotics - They provide live strains of good bacteria to help food digestion and intestinal absorption of nutrients and bolster your immune defenses. [See: Probiotics]

Pulmonary hypertension — elevated or abnormally high blood pressure in the pulmonary arteries of the lungs.

ReverseT3 — triiodothyronine (RT3)RT3 is a metabolite of T4 (thyroxine). Typically, when T4 loses an atom of iodine—a process known as monodeiodination, or T4 to T3 conversion—it becomes triiodothyronine (T3), the active thyroid hormone. But in some cases, the body conserves energy by converting the T4 into RT3, an inactive form of T3 that is incapable of delivering oxygen and energy to the cells, as T3 does. RT3 blocks functional use of T3, a condition that Kent Holtorf, MD calls "cellular hypothyroidism."

Ribonucleic acid (RNA) — also known as messenger RNA, carries instructions from DNA for controlling the synthesis of bio-essential proteins.

S-Adenosyl-l-methionine (SAMe) — A direct metabolite of the essential amino acid L-methionine and the methyl-group donor in the biosynthesis of DNA and RNA, phospholipids, proteins, epinephrine, melatonin, creatine, and other molecules.

Selenium — Selenium is incorporated into proteins to make antioxidant enzymes glutathione peroxidase and thioredoxin reductase. It is also found in three deiodinase enzymes, which convert one thyroid hormone to another and is therfore essential for thyroid function. It also plays a role in regulating the expression of cell-signaling molecules called cytokines, which orchestrate the immune response. (The minimal dose of selenium for TPO (TPOAb) antibody reduction, that results from iodine excess, was established to be 200 mcg daily but an upper limit of 400 mcg has been suggested, without signs of toxicity at levels as high as 724 mcg. Take the selenium on an empty stomach with vitamin E, which works in synergy with selenium, to ensure proper absorption.) Food sources are: tuna, shrimp, sardines, salmon, turkey, cod, chicken, lamb, scallops and beef.

Single alleles — one gene sub-part inherited from one parent, one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.

Synapse — chemical based connection points (nerve fiber end to end junctions, nerve fiber to muscle, etc.) in neural pathways.

Thyroid — a large ductless gland in the neck (by the larynx) that secretes hormones [mostly thyroxine (T4) and triiodothyronine (T3)] regulating growth and development through the rate of metabolism, regulates body energy storage and usage. This gland makes and stores hormones that regulate heart rate, blood pressure, body temperature, stored food conversion into energy, the rate of chemical reactions (metabolism) in the body, mental illness, etc. It is itself regulated by the pituitary gland.

Thyrotropin — a hormone secreted by the pituitary gland that regulates the production of thyroid hormones.

Thyroxine / levothyroxine (T4) — a stored form of hormone secreted by the thyroid gland which regulates metabolism. [See: Thyroid]

Thyroid stimulating hormone (TSH) — a hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body.

Triiodothyronine (T3) — a hormone secreted by the thyroid gland which regulates metabolism. [See: Thyroid]

Ventricular hypertrophy — most frequently referred to as a pathological reaction to cardiovascular disease, or resulting from high blood pressure. It is usually a marker for disease involving the heart.

Vitamin B — are a group of water-soluble interdependent vitamins involved in converting glucose to energy that play important roles in cell metabolism; any of a group of substances (the vitamin B complex ) that are essential for the working of certain enzymes in the body and, while not chemically related, are generally found together in the same foods. [See: B vitamins] They include:

* Source of folate are fruits and vegetables (especially green leafy vegetables), fortified breads and cereals, lentils, chickpeas, asparagus, spinach, and most beans."

Vitamin B2 - Riboflavin

"Vitamin B2 [Riboflavin] is important for FAD and FMN.
Flavin Adenine Dinucleotide [FAD]:

  • Riboflavin [Vitamin B2] is the central component required by all flavoproteins such as the cofactors in Redox biochemical reactions.
    • 1. FAD—Flavin Adenine Dinucleotide [FAD / FADH2]
    • 2. FMN—Flavin Mononucleotide [FMN /FMNH2]
  • The synthesis of the active form of folate (L-methyl folate/5-MTHF) is FADH2 dependent, and FAD is dependent upon Vitamin B2."

Carol S. Savage, MD [Source: Facebook Group | MTHFR Gene Mutation — July 13, 2013 at 12:30pm]

Vitamin-B6 — forms include: Pyridoxine (PN), most common form for vitamin B6 supplement; Pyridoxine 5'-phosphate (PNP); Pyridoxal (PL); Pyridoxal 5'-phosphate (PLP), the metabolically active form (sold as 'P-5-P' vitamin supplement); Pyridoxamine (PM); Pyridoxamine 5'-phosphate (PMP); 4-Pyridoxic acid (PA), the catabolite excreted in urine. It is used in Amino acid metabolism, Gluconeogenesis, Lipid metabolism, Neurotransmitter synthesis, Histamine synthesis, Hemoglobin synthesis and function, and Gene expression which are essential for normal body functions.

"We know that folic acid, vitamin B6, and vitamin B12 are all involved in breaking down homocysteine in the blood. Therefore, increasing your intake of folic acid and B vitamins may lower your homocysteine level."

Vitamin-B9 (folate, folicin, folic-acid) — It is a water-soluble vitamin that is part of the B vitamin family. Its two forms are the naturally occurring Folate found in food and the synthetically produced folic acid used in fortified foods and supplements. Folic acid requires extra effort for the body to convert to the usable folate form. Vitamin-B9 (folate) is necessary for fertility in both men and women; protection against a number of congenital malformations, including neural tube defects of spina bifida and anencephaly; aiding rapid cell division and growth for pregnancy, infancy and wound repair; recycling of homocysteine into usable cystein, glutathione and taurine; maintain proper balance of vitamin B12 and iron; producing healthy red blood cells; synthesizing, repairing and methylating DNA, acting as a cofactor in biological reactions (converting tyrosine to dopamine, tryptophan to serotonin, et cetera); minimizing confusion and depression; decreasing both age-related macular degeneration and mortality due to malaria; and preventing deficiency caused glossitis, diarrhea, anemia or cancers. [See: Top 10 Foods Highest in Vitamin B9]

Vitamin-B12 (Vit B12 / B12) — cyanocobalamin [synthetic] / methylcobalamin [preferred form for metabolism] is important for the normal formation of red blood cells (necessary for oxygen transport in the body) and healthy nerve tissues. It is also used in: metabolism regulation, cell division and immune health. Undetected and untreated vitamin B12 deficiency can lead to anemia, affect memory and thinking (bipolar disorder, mood swings, dementia and Alzheimer's), and even permanent nerve and brain damage. The only dietary source of B12 comes from animal protein's: seafood, milk products (milk, yogurt, cheese, etc.), meat, poultry and eggs. Vitamin B12 is a very difficult vitamin for the body to assimilate and needs optimal digestive conditions for absorption. [See: PROBIOTICS & PREBIOTICS; and B12 Deficiency—Common. Dangerous. Naturally Treatable]

Vitamin D is a secosteroid. Vitamin-D3 — (Forms: [VIT-D3, 1, 25 HYDROXY, D3] and [VIT-D, 25 HYDROXY, D3]) Vit-D is not really a vitamin but is an internally synthesized hormone that affects neuromuscular and immune function [FASEB J. 2014 Jun;28(6):2398-2413. Epub 2014 Feb 20. Vitamin D hormone regulates serotonin synthesis.] and regulates over 900 genes in the body ( "Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone." Vitamin D (Calcitriol), []. Two essential vitamin D3 blood tests (1,25-D3 and 25-D3) are required to judge the functioning of your vitamin D3 metabolism. High 1,25-D3 levels indicate excessive VDR (vitamin D receptor) activation and can indicate an urgent immune response against T-h1 (T-cell helper type 1) intracellular microbes. Do not take forms other than D3 without testing.

Inflammation and vitamin D: the infection connection from the National Center for Biotechnology Information, U.S. National Library of Medicine:
"The level of 25(OH)D does not always reflect the level of 1,25(OH)2D. Assessment of both metabolites often reveals elevated 1,25(OH)2D, indicating abnormal vitamin D endocrine function."
"Some authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms."

Vitamin D metabolism
"The sequential metabolic processes that convert biologically inactive, parental vitamin D into active metabolites begin when vitamin D3 is photosynthesized in the skin or when vitamin D2 or D3 is ingested. Vitamin D is transported to the liver where it is hydroxylated by an enzyme (CYP2R1, also known as cytochrome P450 2R1) to produce 25(OH)D [1]. 25(OH)D is then transported to the kidneys where it is hydroxylated by another enzyme (CYP27B1, formerly 1a-hydroxylase) to produce 1,25(OH)2D. 1,25(OH)2D (also known as calcitriol), the active metabolite, is the most potent steroid hormone in the human body [2]. Feedback mechanisms regulate production of 1,25(OH)2D in the kidneys via serum levels of parathyroid hormone (PTH), fibroblast-like growth factor-23 (FGF23) calcium, and phosphate [3]. 1,25(OH)2D is also produced in many other tissues (e.g., skin, macrophages, colon, pancreas, blood vessels, etc.) by enzymatic actions [4]. The vitamin D binding protein (VDBP) transports 1,25(OH)2D to the vitamin D receptor (VDR) in the cell nucleus [5]. The VDR is a member of the nuclear receptor family of ligand-regulated transcription factors. 1,25(OH)2D binds to the VDR and mediates the transcription of DNA, triggered by signaling proteins, like nuclear factor kappa-B (NFk-B)"