Recently, I have come across transient receptor potential channel (TRP). The definition from Wikipedia states: There are 7 channels total and each channel consists of a few receptors. One channel that caught my eye particularly was TRPV, which is associated with pain, burning, hot, and pungent odor. Ever since taking mb12 by accident (took it before I even knew about methylation/this forum), my body has been very sensitive to irritants. I would often get body rashes, scalp bumps, and tingling sensation from bed sheets/carpets/dust. Sometimes, my scalp or body would start itching without any known issue. Anti-inflammatory supplements like quercetin and bromelain helped with inflammation, but it was only temporary, and I could not take them for a long-term due to different side effects. One observation I have made is that whenever I consume spicy or pungent tasting food (vinegar, mustard, wasabi, jalepenos, banana pepper, fermented food), my body and scalp would start tingling instantly. I always connected them with histamine reaction, but never fully understood why. Also, for some reason, this symptom worsened as I was taking more magnesium. To understand what is going on, it is important to understand the relationship among magnesium, calcium, and vitamin D. I made a post about them here. In a nut shell, too much/frequent magnesium intake decreases serum calcium level. In response to this, parathyroid hormone (PTH) is secreted to initiate osteoclast (break down of bones), pulling bone calcium to the blood. During this process, hydrogen ion is created, which is often referred as "excess acidity." Hydrogen ion activates TRPV1 pathway, which brings a wide range of problems. These problems include apoptosis induction via TGF-B, increased endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), decreased hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor), and increased intracellular calcium level (0). TRPV1 is activated by active ingredients in some foods like garlic (allicin), chili peppers (capsaicin), wasabi (allyl isothiocynate), and vinegar. Too much TRPV1 activation can lead to osteoporosis, joint pains, and heightened sensitivity (1). I noticed that joint pain is frequently brought up in this forum. At the same time, garlic, ACV, and fermented foods are one of most famous superfoods that a lot of people take. All these foods are driving TRPV1 pathway for more pain and inflammation. Continuous TRPV1 activation can result in various cancesr, digestive tract issues, bladder disease, pulmonary inflammation, diabetes, calcification of arteries/veins, and itch (2). There are several prescription strength medications to antagonize TRPV1 pathway, but they are not readily available. Carotenoids have been successful at mediating TRPV1, but they do not interact with capsaicin (3). The list of carotenoids that works for TRPV1 regulation includes lutein and B-carotene. Lycopene did not work for some reason. Another study lists herbal remedies that agonzie or antagonize TRPV1 pathway. Even though too much/frequent TRPV1 activation is unwanted, it is important to keep in mind that inflammation is one of our body's main defense mechanism. One rat study noted that too much inhibition of TRPV1 can lead to a systematic inflammation, rather than localized inflammation (4). Summing up, we can note that both overstimulation and understimulation of TRPV1 can lead to a systematic inflammation. Balance never gets old when it comes to health. TRPV1 agonist/activators (Increases intracellular Ca level): H+ ions (I think this is one of the main reasons why too much acidity hurts our body) Capsaicin (chili pepper) Ginger (derived products, tumeric/curcumin included, lowers inflammation, but increases Ca level) Ginseng (dose dependent, can act as Capsaicin inhibitor as well) Cannobinoids Mustard oil Pungent tasting food Spicy food Heat (above 43 degree celcius - may be why prolonged intense exercise/frequent hot shower is not good) TRPV1 inhibitors Thapsigargin Yohimbie Carotenoids (B-carotene, lutein) Resveratrol (not much study on this...) If you know any other TRPV1 related supplements/ingredients please share them. Thank you.