Let’s Talk Mold
Takeaways from the ISEAI 2019 Inaugural Conference May 2019.
Day 2 with Bob Miller CTN – Part 3 of 3
Genomic Impact on Detox Ability
If you have been following this mini-series on mast cells, NAD/NADPH, inflammation, and detoxification, you should understand why this has taken 3 blogs to convey. Besides the need for some basic background to understand these metabolic and immune processes, the intricacy of their interwovenness precludes brevity. This final layer will not disappoint if you have enjoyed the depth and complexity. If you feel more than a little bewildered, re-read part 1 and 2 before attacking this third installment. If you are wondering when this whole talk on genomics will actually get to genetics, hang in there till the end. Everything prior has been for the purpose of laying a foundation on which genomics will be erected at the end of this blog.
Before we erect the final level of genomics, we have a final foundation to lay, that of the NAD/NADPH system. Nicotinamide Adenine dinucleotide and Nicotinamide adenine dinucleotide phosphate serve as critical participants in metabolism, oxidation/reduction reactions, and electron transfer for energy production. They do so by receiving or donating electrons and hydrogen atoms through our enzymes to other organic molecules. With their help we can alter organic molecules by adding or removing oxygens (oxidation and reduction process respectively). With their help we can transfer electrons released by burning carbohydrates, fats, and proteins in a manner that can then produce usable energy as ATP. NADPH can also be used to produce reactive oxygen species which the immune system uses to attack invaders. Detoxification of external and internal toxins often require these nutrients or else we cannot rid our bodies of them. NAD and NADPH are even being connected to the aging process.
NAD and NADPH differ in structure and function. Their structure differs by NADPH possessing a phosphate. The function of NAD lies more in the production of energy and the mitochondria. The function of NADPH lies more in cellular anti-oxidant function and the production of reactive oxygen species. The enzyme, NOX (NADPH oxidase) uses NADPH to make these reactive oxygen species for a number of reasons including as a chemical warfare of sorts against invading organisms to destroy them. In the right amounts, at the right times, in the right places, they serve a beneficial function.
When too much is produced in the wrong places, disease can result. Such overproduction in the cardiovascular system vessels may contribute to heart and cerebrovascular disease. In the brain, nerve cells may be harmed and even destroyed, contributing to neurodegenerative diseases. If DNA is targeted, cancer may result from mutations induced by the oxidative damage.
Several intrinsic and extrinsic factors stir up the NOX enzyme to make more reactive oxygen species. Histamine itself stimulates NOX and therefore our first connection to mast cells which release histamine arises. Oxalates from food sources or from internal processes may stimulate NOX. Other nutritional sources include excess or mishandled iron, glutamate, and homocysteine. The hormone aldosterone upregulates NOX. External triggers include smoking and EMF (electromagnetic frequency. Even psychosocial stressors stimulate NOX activity.
Regardless of the source, NOX uses NADPH and lowers the available supply for other necessary processes like detoxification. Meanwhile, several downstream results accrue from the upregulation. More free radicals float around with potential to oxidize cell membranes, DNA, or other functioning proteins. Mast cells are upregulated by the free radicals, releasing more cytokines, increasing inflammation, turning up the immune system. Glutamate raises as its conversion to glutamine and to GABA slows. The increased glutamate may over-excite nerve cells triggering anxiety. These are just the effects of which we are currently aware.
Finally, we have an adequate foundation on which to address genetics. By seeing the connections leading up to this point, we can recognize the import of various SNPs (single nucleotide polymorphisms) which slow or speed up different steps in the big picture. Various SNPs in processing iron and the heme protein responsible for carrying it may increase oxidative stress. SNPs in the NOX gene itself may encourage overproduction of ROS. SNPs in histamine production, degradation, and receptors may predispose to disease risks. Glutamate processing SNPs contribute similarly. While not mentioned so far, SNPs in sulfite and sulfate detoxification may be a problem for some. SNPs in a process called autophagy, or cell recycling, are being linked to these processes. Even SNPs which predispose to great effects of EMF are found tied up in this complicated web.
As always, understanding the problems is not enough in functional medicine. We want to know how to alter dysfunctional processes for our patient’s benefit. We look for ways to increase NAD production and maintain balance in the factors noted above. We aim for just the right amount of iron. We evaluate for oxalate excess. We assess for histamine excess and encourage a low histamine diet if needed. We balance glutamate with B6 and magnesium. We encourage patients to avoid preservatives with sulfites. We monitor and modulate methylation. We work on whole person health to lower stress. If patients appear sensitive to EMF, we guide them in lowering exposures.
In summary, as NOX produces more reactive oxygen species, the free radicals stimulate mast cells. The mast cells trigger inflammation which increases reactive oxygen species. Alongside these processes, other chemical or cellular mediators trigger more damage to systems and tissue. Ultimately symptoms result. By addressing upstream factors, we can see magnified beneficial responses. By evaluating SNPs, we can target the weak links in metabolism or look for better options to modulate. We are just on the tip of the iceberg in understanding the interplay between different SNPs and their effects on chronic disease through the NAD/NADPH and Mast cell systems. Functional Medicine doctors like myself looks forward to every discovery which lead to our patients living healthier more abundant lives.