Quote from Dr. Garrett Smith on December 28, 2018, 8:46 pm

Acetazolamide, a carbonic anhydrase inhibitor drug, is used in conventional medicine to relieve the symptoms of Poison/"Vitamin A" toxicity, particularly those related to increased pressure inside the skull.

Acute hypervitaminosis A in a young lady.

Acute vitamin A toxicity from a large dose has been reported to cause pseudotumour cerebri. Usually it is common in children. Herein we present the case of a young lady of 18 years old with the complaints of headache, vomiting, back pain and diplopia after ingestion of high dose (about 10 million international units) vitamin A capsule intentionally at a time due to some family problems. She gave no history of fever, convulsion, unconsciousness, pain in eyes, difficulties in walking and jaundice or any urinary problem during this illness. On query she gave no history of taking any other drugs including oral contraceptive and tetracycline & steroids. She also gave no history of sleep disorder. There was bilateral papilloedema, pupils were a bit dilated symmetrically but reacting to light, visual acuity 6/60 on left eye and 6/18 on right eye and bilateral 6th cranial nerve palsy more marked on left side. MRI of brain and orbits showed normal study. Patient improved after giving acetazolamide.

[Treatment of acne with consequences -- pseudotumor cerebri due to hypervitaminosis A].

Pseudotumor cerebri (PTC) is an entity characterized by elevated intracranial pressure of probably multifactoral origin, but most cases remain idiopathic. We report a 15-year-old girl with PTC due to prolonged consumption of Arovit (Vitamin A) for treatment of acne. The diagnosis was established by measuring raised cerebrospinal fluid pressure after an intracranial mass lesion and dural venous sinsus thrombosis were excluded. The increased level of vitamin A confirmed the diagnosis of hypervitaminosis A as the causative pathogen. The patient was treated with lumbar punctures and acetazolamide (Diamox). PTC due to hypervitaminosis A is a serious complication, which can cause permanent visual impairment. Patients treated with retinoids require proper surveillance. The elevated serum level of retinoids after withdrawal may persist for weeks.

Knowing about this medication and its mechanism of action now, are there any food-based carbonic anhydrase inhibitors that have a longstanding reputation of helping human health and longevity?  Yes, there are multiple.  One that stands out is pomegranate.

Carbonic anhydrase inhibitors from the pericarps of Punica granatum L.

Seven highly active inhibitors against carbonic anhydrase (CA, EC 4.2.1.1), punicalin (2), punicalagin (3), granatin B (5), gallagyldilactone (7), casuarinin (8), pedunculagin (9) and tellimagrandin I (10), and four weakly active inhibitors, gallic acid (1), granatin A (4), corilagin (6) and ellagic acid (11), were isolated from the pericarps of Punica granatum L. (Punicaceae). They are ellagitannins. The type of inhibition by 3 and 7 using p-nitrophenyl acetate as a substrate, is noncompetitive. The structure-activity relationship of inhibitory effects on CA is discussed.

What issues related to Poison/"Vitamin A" toxicity might pomegranates be able to help, based on the research?

A Comprehensive Review of Punica granatum (Pomegranate) Properties in Toxicological, Pharmacological, Cellular and Molecular Biology Researches

Existence of these pharmacological and toxicological mechanisms and properties and interference of several signaling pathways including PI3K/AKT, mTOR, PI3K, Bcl-X, Bax, Bad, MAPK, ERK1/2, P38, JNK, and caspase relation to Pg [pomegranate], suggest that Pg can be extensively used as a possible therapy for prevention and treatment of several types of diseases including prostate cancer, colon cancer, breast cancer, lung cancer, skin cancer, leukemia, anti-atherosclerosis, hyperlipidemia, hypertension, myocardial ischemia, myocardial perfusion, diabetes, oral inflammation, infection, anti-erectile dysfunction, male infertility, neonatal hypoxia-ischemic brain injury, alzheimer and obesity.

Are there any other natural foods/compounds that are also regarded as carbonic anhydrase inhibitors in the research, particularly those that I have identified in other places in this blog=forum as being anti-Poison/"Vitamin A" already, and that are often shown to be longevity-increasing?  Why yes, there are:

In Vitro inhibition of human carbonic anhydrase I and II isozymes with natural phenolic compounds.

Inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II with some natural phenolic derivatives was investigated using the esterase assay with 4-nitrophenyl acetate as substrate. Resveratrol, catechin, silymarin, dobutamin, and curcumin showed K(I) values in the range of 4.47-9.47 mm for hCA I and of 2.86-7.44 μm against hCA II, respectively. These natural product phenols were generally competitive inhibitors with 4-nitrophenylacetate as substrate. Some natural phenols investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms that have not been yet assayed for their interactions with such agents.

If you are not familiar with the compounds mentioned above:

• Resveratrol is an OPC (oligomeric proanthocyanidin, a polyphenol) that is found in many foods, particularly grapes (and in supplements in grape seed extract).  Be wary of overdoing grape seed extract and resveratrol/pynogenol supplements, as it can lower iron levels excessively if too much is taken in supplement form.  Those on my Nutritional Restoration programs get a comprehensive analysis of their iron metabolism and OPCs supplements are used only when needed.  Food OPCs are always OK.
• Catechins are also polyphenols and are found in many foods, the tea plant Camellia sinensis (white, green, black, Oolong, etc., must always be organic) is one of the highest commonly consumed sources.  Some teas are excessively high in fluoride (particularly if they are non-organic), and the high levels of tannins in tea can inhibit iron and other mineral absorption, so this route shouldn't be overdone.  Excessive oxalate consumption from teas can also cause kidney stones in those who also have an excess of calcium floating around their system (we fix the calcium issue with the Nutritional Restoration program).
• Silymarin is found in the herb milk thistle, and is commonly regarded as extremely helpful for the liver.  That said, people who are sensitive to ragweed (seasonal allergies and/or hay fever symptoms is how this shows up) are often found to be sensitive to milk thistle and get hay-fever-like symptoms from it, so it does not work for everyone.
• Curcumin is derived from turmeric and both of these have reams of research (see links) showing them to be helpful in an ever-increasing number of disease conditions.  Not everyone gets along with these though.

And finally, ZINC is a critical component of nearly all carbonic anhydrase inhibitors, and if you search this site, you'll find that zinc is absolutely crucial in the body protecting itself from Poison/"Vitamin A" through the manufacture of the protective Retinol-Binding Proteins (RBPs).

See CARBONIC ANHYDRASE:  Why zinc? and Role of Zinc in Catalytic Activity of Carbonic Anhydrase IX:

The carbonic anhydrases (CAs) in the α class are zinc-dependent metalloenzymes.

So, for proper carbonic anhydrase activity in the body, it could be assumed that proper zinc levels are also necessary.  For proper protection against Poison/"Vitamin A" toxicity via hepatic (liver) production of RBP, zinc is also necessary.  There are no coincidences.  Things you should know about zinc straight away, in my opinion:

• It is difficult to get enough zinc from foods while undergoing Poison/"Vitamin A" detox.  It is quite possible that the noticeable trend in the literature of vegan or heavily vegetarian diets showing patterns of Poison/"Vitamin A" toxicity is at least in part to the diet being very low in zinc (animal products provide the most zinc in foods).
• An excess of supplemental zinc for too long can easily drive depletion of copper causing a whole new problem of copper deficiency. I have observed distinct patterns of certain parts of the world having major trends towards either copper excess OR copper deficiency, and we TEST, we don't GUESS, to figure this out for each INDIVIDUAL person based on my Nutritional Restoration work.
• Through the proper use of zinc- and copper-related bloodwork--NOT hair mineral analysis as it utterly fails in the zinc/copper assessment arena, I've used both and have a very strong experience-backed opinion on this--a person's long-term need for supplemental zinc (or not) can be figured out over time.  Zinc and copper analysis via bloodwork, along with iron-related bloodwork, are the most important nutritionally-related blood tests one can do...hair mineral analysis is good for many other minerals, just NOT THOSE THREE.

As usual, we can use the "conventional" research to reverse-engineer what works and how to do these things in the most effective ways possible. While you can experiment on your own, many people find it quite helpful to have the full range of my clinical experience and the Nutritional Restoration testing to help guide them through the process.