Chronic stress, immune imbalance, and thyroid dysfunction are deeply interconnected. This forms a stress–immune–thyroid triad where each system influences the others, affecting energy, mood, and resilience. Research shows that targeted support—including adaptogens, micronutrients can help restore communication across this network. Rather than offering quick fixes, this systems-based approach addresses underlying feedback loops, combining clinical insight, patient engagement, and supportive lifestyle practices to rebuild physiological balance and improve well-being over time.
Laura Lewis, MS
Cofactors are essentially helper molecules that allow biochemical reactions to occur. Some cofactors are inorganic metal ions such as iron and magnesium. Organic (carbon-containing) cofactors are sometimes classified more specifically as “coenzymes”. Coenzymes primarily assist the action of enzymes, but these words are generally interchangeable. All of the water-soluble vitamins (Bs and C), and two fat-soluble vitamins (A and K) fall into this category of coenzymes/cofactors. [1]
What do Cofactors do?
Vitamin cofactors play a role in a multitude of biochemical reactions involving energy metabolism. They are also necessary for processes necessary for proper vision, blood coagulation, hormone production, and the integrity of collagen. [1] Collagen is a protein found in bones, skin, cartilage, and other structural tissues. [1]
Some cofactors function by ferrying electrons or negative charges to enhance a reaction. Vitamins B2, B3, and C are all precursors of electron-carrying coenzymes. Vitamin C (ascorbic acid) is a cofactor for the hydroxylase enzymes. These are the enzymes that support the structural integrity of collagen, the hydroxylation of cholesterol to form bile acids, and the synthesis of norepinephrine (noradrenaline) from the amino acid tyrosine. [1]
Three activated forms of riboflavin (vitamin B2) serve as hydrogen carriers to assist in the Kreb’s also known as the citric acid cycle. This biological process produces cellular energy. The vitamin cofactor forms of niacin (B3) play a role in the catabolism of fat, carbohydrates, and amino acids, and in the enzymes involved in the synthesis of fats, steroids, and other vital metabolites.
B5 (Pantothenic acid) is a component of coenzyme A. Coenzyme A is necessary for the metabolism of carbohydrates, amino acids, fatty acids, and other biomolecules as well as the synthesis of fatty acids.
Vitamin B6 has two coenzyme forms that serve as cofactors in over 120 enzyme reactions (too many to list here). Vitamin B12 serves as an important cofactor in methylation: converting homocysteine to methionine and recycling the methyl group from Methylfolate. Folate then can be converted into its coenzyme form, allowing for amino acid conversion reactions and the synthesis of nucleic acids, RNA and DNA. [1]
L-Methylfolate does not work alone in your cells. It needs a number of cofactors present at adequate levels to do its job. The most important cofactors for folate are B6 and B12.
Homocysteine levels can build up in the blood without vitamin B6, as B6 aids in glutathione synthesis using homocysteine. [2] Healthy homocysteine levels are associated with a healthy cardiovascular system, among other health benefits.
B12 deficiency can also halt the same cycle, but by preventing homocysteine’s transformation to methionine. L-Methylfolate and B12 are essentially coenzymes in the folate methylation process. More specifically, methionine synthase catalyzes the primary remethylation pathway with the help of vitamin B12 and activated folic acid (L-Methylfolate). [3]
Magnesium a cofactor in more than 325 enzymatic reactions and about two-thirds of the American population are estimated to be magnesium deficient. [4] Magnesium is a cofactor for the COMT enzyme, which transfers a methyl group from SAMe to metabolize dopamine, norepinephrine, and epinephrine. [4]
Cofactors and Mood Support
Unfortunately, there is a vicious cycle when it comes to stress and nutrition. Vitamins and minerals, including magnesium, are used more quickly in the body in states of physical and mental stress. [5] When you need the benefits of nutrition the most, nutrients are typically less available.
Knowing this, when you are under stress, you may want to support your micronutrient intake. This may be especially important for the cofactors necessary to assist in the process of methylation. Your mood may also be uniquely difficult to keep balanced under stress, in part due to the availability of nutrition.
Specifically, magnesium is a great stress and mood support mineral. Not only is it necessary for methylation and downstream processes, it also plays a role in the relaxation of muscles and physical calming of the body.* [6] On top of these, magnesium offers benefits to bones, energy, the cardiovascular system, muscular system, dental health, insulin signaling, and general emotions.* [6]
Disclaimer:
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
Laura Lewis is a clinical researcher and science communicator with a Master of Science degree and a background in nutrition science and integrative health. She brings a decade of experience translating complex clinical data into accessible insights for healthcare practitioners and patients alike.
Laura has contributed to educational programming and strategic content development across the integrative and functional medicine space. Her strengths lie in evidence synthesis, practitioner engagement, and crafting communications that bridge the gap between scientific rigor and real-world application. At ARG, Laura supports clinical content development and educational initiatives that elevate practitioner confidence and product credibility.