Insights on Clinically Actionable Genes

By: WellnessWiz Jack Tips Ph.D., C.C.N.

MTHFR C677T & A11298C

Methylenetetrahydrofolate Reductase

Gene-activation of Vitamin B9 (Folate) – Quatrefolic Acid (L-5 MTHF)

Significance: Governs the ability of the cells and cellular organelles to employ folate metabolically for various cellular activities such as detoxification, recycling glutathione, repair, and much more. SNPs (Single Nucleotide Polymorphisms) on the MTHFR gene can result in the cellular tendency to accumulate environmental toxins which disrupt metabolic processes and damage cellular performance. The body’s innate ability to “methylate” – add a methyl molecule (CH3) to a gene – silences that gene’s expression. The removal of that CH3 molecule from a gene allows that gene’s active transcription. Thus, methyl molecules are the genetic “on/off switches.”

methyl molecules are genetic on/off switches

Gene Test: Systemic Detoxification Profile with GIS (Genetic Impact Score). The Detoxification Report provides in-depth analysis and actionable1 insights.

Blood Tests: Methylation Profile: B1 (Thiamin), B2 (Riboflavin), B3 (Niacin), B6 (Pyridoxine), B9 Folate, B12 (Cobalamin), Cystathionine, Cysteine, Homocysteine, Methionine, SAMe (S-Adenosyl-L-methionine), SAH (S-Adenosylmethionine).


The methylation process, one of the great secrets of life, is profoundly important to our holistic health – mental, emotional, and physical adaptability and survival. Integral to this vital process is the B vitamin, folate.

Perspective: On Earth, every living organism is made from carbon atoms. Most have bonds with hydrogen, though a few are bound to oxygen (O), nitrogen (N), and sulfur (S). When a single carbon atom (C) attaches to three hydrogen (H) atoms, it becomes a “methyl  group” (CH3). Methylation is the transfer-process or “donation” of methyl groups—a molecular game changer involving a hydrogen atom.

Demands For Methylation: Most of the body’s methylation activity is to synthesize two molecules: 1) Creatine, and 2) Phosphatidylcholine.

  • Creatine supports muscle-building and repair, is necessary for digestion via hydrochloric acid, supports sperm motility (reproduction), and is vital to the sensory processes—vision and hearing.
  • Phosphatidylcholine is a necessary component of the cell membranes (lipid-bilayer) for cellular energy and respiration; and serves the liver regarding lipid metabolics. Deficiency can result in poor cell membrane and organelle performance as well as all forms of fatty liver disease which are becoming pandemic in the human population. It is also a critically important raw material for the neurotransmitter, acetylcholine, necessary for proper brain function.

Hypo & Hyper Methylation

On the methylation bell curve, most people with issues are hypo (under) methylators, but a few are hyper (over) methylators. With methylation, genes, epigenetics, environmental, and life challenges intersect with the body’s innate cellular responses to “adapt and survive.” Each extreme has its challenges that affect a person’s quality of life and longevity. As with all facets of life, balance in all things.

The body has complex, innate mechanisms to balance the methylation processes. The amino acid glycine and the antioxidant tri-methyl-glycine serve to buffer and help regulate methylation for optimal health. One concern of the deadly herbicide, glyphosate, is that it takes a toll on the body’s glycine supplies risking cellular depletion of glycine. Low glycine levels are associated with irregular blood sugar processes, poor sleep patterns, osteoporosis, and skin  wrinkles. Thus supporting methylation and trimethylglycine simultaneously is a smart way to supplement in today’s environment.

Selenomethionine & Thiolactone Reductase

Another way to supplement for balanced methylation processes is the nutrient selenomethionine which provides both selenium and the amino acid methionine which becomes the universal methyl donor via the cells’ ATP (Adenosine Tri-Phosphate) energy creation homocysteine cycle.

When this fundamental life process lacks core nutrients, the body can suffer from thiolactone toxicity, the reason that savvy clinicians want to know a person’s homocysteine blood levels to assess cardiovascular health and if the beneficial thiolactone reductase system can benefit from nutritional support via actionable B-Vitamins and strategic herbs.

Both Vitamins B9 and B12 are necessary to recycle homocysteine back to methionine, and methylation processes are right in the middle of the process. Also Trimethylglycine Betaine, TMG), helps recycle homocysteine back to methionine along with other B vitamins (B1, B2, B3,  B6) support the process.

Re-methylation pathway

Science has discovered a window into understanding a component of the “acquired disease process.” Thoughts, emotions, environmental toxins (chemicals) can cause activation of a disease process. For the body to stop that, when the cause(s) are first addressed, it will silence the alarm with a methyl molecule.

Folate 🡪 Methylation Importance

  • Repair and construct DNA and RNA
  • Detoxify histamine
  • Adapt to the environment
  • Allow mental flexibility, cognition
  • Protect the cells’ telomeres and genetic material that impact aging
  • Regulate cellular energy
  • Repair cell membranes and nerve sheaths
  • Support proper allergic responses
  • Construct immune cells
  • Produce glutathione (protect and detox cells)
  • Hormone regulation and balance
  • Support detoxification of chemicals and heavy metals
  • Modulate intracellular stress responses
  • Regulate the brain’s neurotransmitters for mood, brain function, and sleep
  • Support healthy weight management
  • And many more


Folate, Not Folic Acid. The proper term for Vitamin B9 is Folate. It’s not the same as the undesirable compound, folic acid, but outdated science, food producers (flour, bread), and vitamin manufacturers have errantly employed folic acid thinking that they were the same. Folate is what plants and the gut-microbiome make for cellular nutrition. Folic Acid is a synthetic vitamin that taxes (and even damages) the liver to process it into folate, and folic acid reacts with heavy  metals and the ubiquitous herbicide, glyphosate, metals to block folate synthesis and utilization, in the liver and in the brain. Folic acid depletes the master antioxidant, Glutathione, leaving the cells more susceptible to free-radical pathologies.

the promise of epigenetics

Epigenetic Implementations. A person’s innate epigenetic responses transcribe gene information into cellular metabolic proteins via a complex, interrelated gestalt based on thoughts, feelings, beliefs, stresses, environment (nature vs. nurture), exposures (toxins, pathogens vs. HerbalomicTM 2 plant components), and is modified by the actions of many other genes. The good news is, even if there is a gene variance (e.g. SNP), a person is not doomed to expressing it!

Promise of Epigenetics. Epigenetic expression of a cellular activity that causes uncomfortable symptoms (dis-ease), can be turned off and the body can stop expressing that dis-ease and return to a more optimal state of metabolic health, if/when the causes are corrected.

MTHFR Risk Alleles

Blinders & Mistakes

Although the human genome contains some 40 methyl-folate genes plus hundreds of other genes involved in methylation activities (CBS, COMT, PON1, CYP1A2, SUOX,  UGT1A1, MTR, NAT2, MTRR, MTHFD1L, and many more), science has focused on just two risk alleles—C677T and A1298C—with thousands of research studies. Thus a science in its infancy.

Here, we’re discussing those two risk alleles, with the admonishment to look at a broader picture and never base supplementation on looking at just these two most-studied risk alleles.

MTHFR Gene-Variant SNP rs Number Risk Allele
MTHFR C677T 1801133 A
MTHFR A1298C 1801131 G

Clinical Implementation

The Systemic Gene Report (Detox Section) supports understanding these two genes in light of some 130 other genes and applies the GIS (Genetic Impact Score) Artificial Intelligence Algorithm to evaluate their impact on hundreds-of-millions of permutations involving other genes. Here we see the importance of a whole genome sequencing rather than a spot-check “chip” reader view of a few genes.

Simply put, with “Person A,” homozygous SNP’s in A1298C can be of little consequence; but in “Person B,” the homozygous SNP’s in that risk allele can be of huge consequence. It all depends on the “whole genome” impact. This is a testimony to biochemical individuality.


For those new to this terminology: everyone has two alleles (alternative forms of a gene that can occupy the same position on a  chromosome), one from Mom and one from Pop.

  • Homozygous means that the person has identical pairs of alleles for any gene pair of heredity characteristics, thus a phenotype3 of + + or – – .
  • Heterozygous means having a dissimilar pair of alleles for a particular heredity trait, thus a phenotype of + – or – +.
Homozygous vs. Heterozygous

Practitioners who simply look at a couple of MTHFR genes and recommend stout doses of methylfolate often do a great disservice to their patients as evidenced by aggravations. Thus the admonishment, “A little knowledge is a dangerous thing,” and becomes a powerful affirmation of the holistic model rather than the fragmented, isolated model of health and disease so commonly practiced today.

The Natural Health perspective to look at the whole person helps put these two risk alleles into proper perspective, clearly identified by the GIS (Gene Impact Score.) This makes it a snap for practitioners to support the most important, actionable SNP’s with the proper dosages!

Most Important SNP – C677T Risk Allele

To date, scientific data and publications support that, regarding converting Folate for cellular life processes, the C677T risk allele is the most important one. Following that, though to a lesser extent, is the A1298C risk allele. The actionable nutrient for both of these risk alleles is Methyl-Folate, with the reminder to view these two risk alleles with the understanding that the methylation processes are dependent upon many other B-vitamins and nutrients.

MTHFR Methylation – A Big Risk Factor In Many Concerns:

  • ALS (Lou Gehrig’s Disease)
  • Alzheimer’s
  • Anxiety
  • Atherosclerosis
  • Autoimmune diseases
  • Autism
  • Bipolar disorder
  • Blood clots
  • Blood vessel damage cancer
  • Celiac disease
  • Chronic degenerative diseases
  • Chronic fatigue
  • Depression
  • Diabetes
  • Down syndrome
  • Fibromyalgia
  • Gestational diabetes
  • Homocystinuria (HCY)
  • Inflammatory diseases
  • Lupus erythematosus
  • Migraines
  • Miscarriages
  • Mitochondrial diseases
  • Multiple sclerosis (MS)
  • Neural tube defects
  • Parkinson’s disease
  • Schizophrenia

So it’s fair to say, “practically everything.”

What To Do?

  1. Systemic Formulas has pioneered two methylation-specific formulas: the flagship MORS  (Methylation Donors) (capsules and liquid for micro-dosing), and the specific Homocysteine TLR (Thiolactone Redux Support).
  2. Exercise – Research supports exercise as improving methylation processes.
  3. Foods that support methylation – organic, leafy green vegetables, organic beets, raw organic broccoli, free-range or organically raised eggs, grass-fed beef, organic citrus fruit.
  4. Avoid foods that interfere: alcoholic beverages, gluten, soy, sugar, refined carbohydrates.
  5. Reduce exposure to plastics.
  6. Avoid Folic Acid (in commercial breads and irresponsible supplements).

Empowered By Gene Knowledge

Knowing if a cell’s fundamental metabolic processes are supported or inhibited by a certain gene provides the clinician keen insights on how to naturally support cellular health, prevent disease, and extend longevity via actionable nutrients.

Q. Who Needs To Know Their MTHFR Status?

A. People Who Want To Be Proactive Regarding:

  • Longevity
  • Lifestyle improvements for more optimal detoxification processes
  • People who want to prevent diseases as they age
  • People who want to reverse symptoms and have a chance for their bodies to “self-correct”
  • People with symptoms. (Emphasizing that “everyone” is the substantiated answer)

Knowledge Is Power

The Systemic Gene Test and resulting Gene Report in the hands of trained natural health professionals are powerful, clinical tools that are revolutionizing Functional Medicine and Clinical Nutrition with science-backed authority to employ supplements for more optimal health, longevity, and prevention of disease.

High Demand

Gene Testing is in high demand. Patients want to know. Early-responding clinicians are seeing a dramatic increase in their case-loads and revenue; but most importantly, gene testing provides a clinically-responsible, actionable basis for natural health advice.

What Now? Action-Item Checklist:

  • Enroll in the Systemic Gene Test Program and implement with your patients. Click Here for more info and to enroll.
  • Get your personal Gene Report. Order your kit at 800-445-4647.


  1. Actionable – Scientific validation that a decision can be made, and action taken, because there is sufficient grounds for that action. E.g. Scientific study proves the beneficial impact of herbal, nutriment (vitamin, mineral, nutrient) supplementation regarding a gene report’s identification of gene expressions. 
  2. Herbalomics™ – the epigenetic impact of botanical molecules on DNA expressions of health and disease. © by Dr. Shayne Morris. Reveals “actionable” nutrients based on scientific studies.
  3. Phenotype – an organism’s actual observed properties, e.g. form, structure, development, behavior.