Metabolic Maintenance

SAMe Plus Cofactors

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SAMe is a critical methyl donor for several important reactions in the body including the formation of healthy levels of neurotransmitters. Other nutrients contribute to the cycle of methylation reactions as well. We offer SAMe with its nutrient cofactors to provide an easy-to-take product to support methylation processes in the body.

  • Promotes the conversion of homocysteine back to SAMe*
  • Nourishes healthy neurotransmitter formation*
  • Supports balanced mood*

Product Information

SAMe Plus Cofactors 200 mg


Product Code: 00156            Capsules per Bottle: 60


Each size 00 acid-resistant vegetarian cellulose and gellan gum capsule contains:


Vitamin B-6 (as Pyridoxal 5 Phosphate)

2 mg

Folate (200 mcg from L-5-Methylfolate, glucosamine salt)

333 mcg DFE

Vitamin B-12 (as Methylcobalamin)

500 mcg

Calcium (as Calcium Citrate)

20 mg

Magnesium (as Magnesium Citrate)

20 mg

SAMe (from 444 mg S-Adenosyl-methionine-disulfate-p- toluensulfonate, calcium chloride, calcium oxide)

200 mg

Other ingredients: L-leucine, (capsule contains gallen gum.)


What is SAMe Plus Cofactors?

SAMe (pronounced like the name “Sammy”), or S-Adenosyl-L-methionine, is a metabolite of the amino acid L-methionine and can be found in all cells of the body. SAMe is a substrate crucial to three central metabolic pathways: methylation; transsulfuration; and transaminopropylation. The transsulfuration pathway ultimately leads to the synthesis of glutathione, a cellular antioxidant involved in numerous biological functions. SAMe plays a crucial biochemical role as a methyl donor in the synthesis of neurotransmitters, nucleic acids, phospholipids, and proteins [1]. 

Through these pathways, SAMe is also involved in the synthesis of proteoglycans for cartilage, myelination, and synthesis of carnitine, coenzyme Q10, and creatinine, the formation of cysteine, other endogenous anti-inflammatory, neurotrophic, and antioxidant molecules, as well as the synthesis, repair, and recombination of DNA [2].

SAMe has been shown to exert anti-inflammatory activity in patients affected with osteoarthritis [1]. Finally, other studies demonstrated its activity in supporting liver health in those with alcoholic hepatitis and cirrhosis [1].

Cofactors are essentially helper molecules that allow biochemical reactions to occur. SAMe cannot participate in these important biological pathways without the help of vitamins B-6, B-12, and folate, as well as the mineral magnesium. This formula contains these cofactors as well if their presence in your diet does not meet the requirements of the same processes requiring supplemental SAMe. 


How does SAMe Plus Cofactors Work?

Since its discovery, SAMe has been extensively studied for its ability to promote a positive mood and emotional balance, but the precise mechanism of this effect is still somewhat unclear [1]. 

It is known, however, that SAMe does cross the blood brain barrier, and when distributed to the brain, it stimulates the activity of dopaminergic and serotonergic pathways, probably through its involvement in transmethylation processes. We also know that SAMe-dependent methylation reactions are required for our cells to make all of the positivity and alertness-associated neurotransmitters: dopamine, serotonin, epinephrine, and norepinephrine. The networks of neurons that respond to the messages sent by these neurotransmitters are involved in the regulation of cognitive processes such as emotion, arousal, and certain types of memory. 

In the midst of mood-related research, scientists noted that SAMe treatments also lead to improved arthritis symptoms—an unintended, positive side effect. Many years and numerous clinical studies later, we now know that SAMe is about as effective as standard anti-inflammatory drugs (i.e. ibuprofen) in easing the symptoms of osteoarthritis [3,4]. Because of these findings, for the last 20 years, SAMe has been touted in the US as a dietary supplement that promotes joint health, mobility, and joint comfort [5]. In a similar manner to a glucosamine and chondroitin regimen, the response to SAMe is very long-lasting and suggests that this nutrient has a deeper impact on osteoarthritis than simply relieving symptoms. It is likely that SAMe also has a protective effect against damage to cartilage [3].

In all cells, SAMe is involved in the biosynthesis of phospholipids which play several important roles within the cell membrane. These roles include regulation of cellular enzymatic and bioelectrical activity and the maintenance of membrane fluidity. Membrane fluidity, specifically in brain cells has been linked with the efficacy of binding sites for neurotransmitters like dopamine and stress signals [2]. SAMe supplementation helps to maintain normal phospholipid ratios and restores enzymatic activity leading to normalization of metabolic processes within the cell. This may also explain, at least in part, the effect of SAMe on boosting hepatic (liver) function, as chronic liver disease has been shown to cause changes in cell membrane composition and enzymatic activity of hepatocytes [2]. Glutathione is also a key player in detoxification within the liver, and SAMe supports the transsulfuration pathway that leads to glutathione production, preventing depletion of glutathione stores, normalizing mitochondrial enzyme activity, and preventing the production of acetaldehyde and deposition of fat in the liver [1].

Vitamins B-6, B-12, and folate are necessary cofactors in the methylation cycle, allowing the reactions required for SAMe’s benefits. They are provided in this formula in their bio-active forms: pyridoxal 5 phosphate, methylcobalamin, and L-methylfolate. Magnesium is a cofactor for neurotransmitter synthesis and transmission.


What is the Suggested Use for SAMe Plus Cofactors?

  • Mood and brain health. SAMe-dependent methylation reactions are vital for the synthesis of neurotransmitters: dopamine, serotonin, epinephrine, and norepinephrine. SAMe is also needed for phosphatidylcholine production which is vital for cell membrane fluidity and central nervous system function. SAMe deficiency has been reported in patients with inherited defects in folate and methionine metabolism (such as MTHFR mutations) as well as in common diseases such as depressive disorders, Alzheimer's Dementia, Parkinson's Disease, and HIV [6]. Supplementation can help to combat these deficiencies.
  • Joint health. SAMe has been shown to promote joint comfort by increasing the production of proteoglycans and reducing inflammatory mediators, among other effects.
  • Liver health. SAMe contributes to the fluidity of liver cell lipid membranes, plays a role in detoxification pathways, and increases hepatic glutathione levels for liver health. 
  • SAMe cannot participate in these important biological functions without the presence of vitamins B-6, B-12, and folate, as well as the mineral magnesium. This formula contains these cofactors as well.
  • Our capsules are acid-resistant to protect SAMe from the low pH of the stomach and deliver it to the small intestine where it is absorbed. Metabolic Maintenance uses SAMe stabilized with calcium made by Gnosis-Bio in Italy. It does not require refrigeration or coatings.


Source Materials: SAMe, methylcobalamin and L-leucine are made by fermentation. Pyridoxal 5 phosphate and L-methylfolate are made by chemical synthesis. Calcium and magnesium are mined minerals. Citric acid (for citrates) is made by fermentation of corn sugar. Cellulose for capsules is derived from softwood tree pulp. Gellan gum for acid resistant capsules is made by fermentation with Pseudomonas elodea. All ingredients are vegan and non-GMO.


Allergens: According to information provided by our suppliers, these capsules are free of the eight major allergens as identified by the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA): Wheat (gluten), eggs, milk, soybeans, shellfish, fish, peanuts, tree nuts.


Recommendations: One to two (1-2) capsules daily, between meals, or as directed by a healthcare professional.


Precautions: Pregnant or lactating women and individuals taking prescription medications should consult with a healthcare professional before taking any supplement. If you suffer from bipolar (manic) depression, do not use this product.

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