Citrulline (name derived from citrullus, the Latin word for watermelon, from which it was first isolated) is an amino acid. It is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by nitric oxide synthase (NOS) family. Citrulline supplements have been claimed to promote energy levels, stimulate the immune system and help detoxify ammonia (a cell toxin). Citrulline is not involved in protein synthesis. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations (for example in case of malnourishment), because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Citrulline is converted to L-arginine by argininosuccinate synthase. L-arginine is in turn responsible for citrulline's therapeutic effects. Many of L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide (NO).

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme required for the formation of 5-methyltetrahydrofolate (5-MTHF), a form of folate able to cross the blood-brain barrier and which is necessary as a substrate for the remethylation of homocysteine to methionine by methionine synthase. Patients with severe MTHFR deficiency cannot make 5-MTHF and have extremely low levels in the CSF. Only treatment with oral 5-MTHF given as calcium mefolinate resulted in an increase in CSF 5-MTHF.

D-ribose, a naturally occurring pentose carbohydrate, and a key component in the adenosine triphosphate (ATP) molecule. D-ribose was studied for congestive heart failure. In addition was discovered, that D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome. Recently was published an article where were described, that d-Ribose reacted with the N-terminal valinyl residues of hemoglobin (Hb), thus producing glycated hemoglobin (HbA1c). It is known, that HbA1c is the most important marker of hyperglycemia in diabetes mellitus, which prompts future studies to explore whether D-ribose could also lead to diabetic complications.

D-mannose is a simple sugar found naturally in fruits such as cranberries and pineapples. Unlike many sugars, it is not metabolised or stored in the liver. Much of it is excreted in the urine, where it interferes with particle attachment and prevents certain kind of bacteria from sticking to the walls and causing infection. Mannose supplement is also indicated for treatment of carbohydrate-deficient glycoprotein syndrome, however clinical trials failed to prove its efficacy.

DB00144 (1-propionyl-2-butyl phosphatidylserine) is a phosphatidylserine derivative. It consists of a propionic and butyric acid residues attached in ester linkage to the first and second carbon of glycerol and serine attached through a phosphodiester linkage to the third carbon of the glycerol. DB00144 is not found in natural sources of phosphatidylserine, which contain fatty acids with a length of 20-22 carbon atoms. DB00144 was detected as one of the cellular metabolites in murine myocardium.

Flavin adenine dinucleotide is a coenzyme form of vitamin B2. Many oxidoreductases, called flavoenzymes or flavoproteins, require FAD as a prosthetic group, which functions in electron transfers. It is usually used for the prevention and treatment of various diseases that are caused by Vitamin B2 deficiency or metabolic disorder including stomatitis, eczema, etc. No adverse reactions were reported.

Cocarboxylase is the coenzyme form of Vitamin B1 present in many animal tissues. Thiamine pyrophosphate (cocarboxylase) is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. Pancreatic cells obtain thiamin from their surroundings and enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP is then taken up by mitochondria via a specific carrier the mitochondrial TPP transporter (MTPPT; product of the SLC25A19 gene).

Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate) is a molecule that is important in many biological processes; it is derived from adenosine triphosphate (ATP) by adenylate cyclase located on the inner side of the plasma membrane and anchored at various locations in the interior of the cell. Around 1960 Earl W. Sutherland, Jr. showed that cyclic adenosine monophosphate (cAMP) serves as the secondary messenger within the cell. Cyclic AMP works by activating protein kinase A (PKA, or cAMP-dependent protein kinase). PKA is normally inactive as a tetrameric holoenzyme, consisting of two catalytic and two regulatory units with the regulatory units blocking the catalytic centers of the catalytic units. Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus enabling those catalytic units to phosphorylate substrate proteins. It was discovered, that melanocytes require the RAS/RAF/MEK/ERK and the cyclic AMP (cAMP) signaling pathways to maintain the fine balance between proliferation and differentiation. cAMP suppressed CRAF activity in melanocytes and that was essential to suppress the oncogenic potential of CRAF in the cells. When RAS was mutated in melanoma, the cells switched their signaling from BRAF to CRAF. That switch was accompanied by dysregulated cAMP signaling, a step that was necessary to allow CRAF to signal to MEK. Thus, a fundamental switch in RAF isoform usage occurs when RAS was mutated in melanoma, and that occurs in the context of disrupted cAMP signaling. These data have important implications for the development of therapeutic strategies to treat this life-threatening disease.