Dr. Jonathan Wright has always had an eye out for research that suggests new diagnostic and therapeutic approaches. He believes that understanding the body’s inherent biochemistry can reveal novel treatments with the potential for doing good without doing harm. He brings this way of thinking to the development of laboratory testing, looking for diagnostic approaches that will yield earlier detection of potential problems. Early detection allows for early intervention in the disease process, when it is most possible to slow or reverse the course of disease. In addition to keeping up with current research, Dr. Wright has a vast database of older, still valid research, to draw on.
Xanthurenic (XANA) and Kynurenic Acid (KYNA) are metabolites on the Kynurenine Pathway of tryptophan metabolism. MVL has added Xanthurenic and Kynurenic Acid to its profiles to improve the clinical management of estrogen detoxification.Studies indicate that individuals with low-activity catechol-O-methyltransferase (COMT) may require additional B6, B12 and folate to detoxify pro-carcinogenic estrogen metabolites. While high levels of Xanthurenic and Kynurenic Acid are commonly associated with mild or subclinical B6 deficiency and/or inflammation, the vitamin B2 requirement for XANA synthesis is seldom discussed or acknowledged in other laboratory reports. Additional risks represented by increased levels of XANA or KANA are also rarely discussed, though equally important:
Insulin resistance and diabetes
• High levels of XANA may form complexes that block insulin receptors and, over time, destroy pancreatic cells.
Cancer risk
• KYNA, and to a lesser extent, XANA both bind to and activate the aryl hydrocarbon receptor (AhR). Activation of the AhR either by environmental toxins (dioxin, etc.) or XANA and KYNA can induce cell damage and carcinogenesis.
Neurologic function
• KYNA blocks glutamate from binding with N-methyl-D-aspartate (NMDA) receptors on neurons, which may alter mood or behavior. KYNA also binds to the alpha7-nicotinic acetylcholine receptor important for long-term memory.
Cardiovascular function
• Higher XANA levels are associated with cardiovascular disease. Chronic inflammation may increase the amount of circulating tryptophan metabolized outside of the liver. Peripheral metabolism of tryptophan in leucocytes, endothelial cells, macrophages and vascular smooth muscle cells increase risk factors for atherosclerosis in those with elevated LDL-cholesterol, BMI, or triglycerides, particularly in younger women.
Autoimmunity
• KYNA levels modulate the production of IL-6 and increased levels of IL-6 are associated with rheumatoid arthritis (RA), systemic-onset juvenile chronic arthritis (JCA), osteoporosis, and psoriasis.
The Kynurenine Pathway metabolizes excess tryptophan and controls hepatic heme synthesis and tryptophan availability for serotonin synthesis. The Kynurenic Pathway also produces immune-regulatory and neuroactive metabolites, nicotinic acid (vitamin B3), and oxidized nicotinamide adenine dinucleotide (NAD+). During homeostasis, the primary site of Kynurenic Pathway activity is the liver, where all of the enzymes to metabolize tryptophan into NAD+ are found, and account for 90% of tryptophan metabolism. During chronic inflammation, the extra-hepatic metabolism of tryptophan increases, and B6 levels decrease. Pro-inflammatory cytokines, combined with lower B6 levels, shift the Kynurenic pathway to produce more Xanthurenic and Kynurenic Acid (see diagram). Conversely, low levels of both Xanthurenic and Kynurenic Acid may indicate a tryptophan deficiency, a liver disorder, or a very rarely, severe B6 deficiency.
Taurine is chemically, a very simple compound, but its affects on cells is both wide-ranging and profound. It is found in high concentration in most human tissues, and is particularly high in cardiac and skeletal tissue. A person’s risk of dying from cardiovascular disease is higher if they have low 24-hour urine taurine. In studies of thousands of men and women in 22 countries, researchers found the highest mortality from heart disease in populations with the lowest 24-hour urine taurine levels. Various studies have shown that 24-hour urine taurine is a reliable biomarker for cardiovascular disease mortality risk.
Here are a some additional facts about Taurine:
• Physiological functions of taurine include maintenance of contractile function, osmoregulation, conjugation, antioxidant activity, membrane stabilization, and protein phosphorylation.
• Although most dilated cardiomyopathies are irreversible, taurine-deficient cardiomyopathy can be reversed with taurine supplementation.
• Taurine has been approved for the treatment of congestive heart failure in Japan, and shows promise for the treatment of several other diseases.
• Osmoregulation by taurine is an important factor of cell survival of all types.
• Taurine supplementation has been linked to decreased BMI and reduced inflammatory markers in obese women.
Testosterone Metabolites Profile
The Testosterone Metabolites Profile is recommended when there is a concern about prostate cancer risk. It measures a number of testosterone metabolites, including 5-alpha DHT and the highly protective 3-beta Adiol, as well as the ratio of 3-beta Adiol to 3-alpha adiol + DHT.
Xanthurenic and Kynurenic Acids
A deeper understanding of these biomarkers provides an early warning system regarding a wide variety of health risks including blood sugar metabolism, cancer risk, depression, cardiovascular disease, and more.
Neutrophilic Segmentation Profile
The relatively short lifespan of a neutrophil allows for a more rapid response to B12 or folate supplementation, and quick follow-up evaluation to supplementation may be of benefit when working up patients with macrocytic anemias or other conditions associated with B-12/folate deficiency.
