Hypothesis: A cognitive benefit seen in the "red wine paradox" might be also obtained by delivering Tylenol directly to the veins in conjunction with consuming the right polyphenols

I don't drink alcohol because of my religion. The Word of Wisdom (Doctrine and Covenants 89) counsels against "strong drink." So for years I read about the "red wine paradox" seen in France--the phenomenon of moderate red wine consumption being protective against cognitive decline (see Nooyens AC, Bueno-de-Mesquita HB, van Gelder BM, van Boxtel MP, Verschuren WM. Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study. Br J Nutr. 2014 Feb;111(4):715-23. doi: 10.1017/S0007114513002845.)--and wondered how I could get the same effect without actually drinking wine. I looked at many of the different polyphenols that could be involved, and quercetin seemed like a good candidate. But studies with these compounds in rats and mice that looked promising never seemed to work out for humans in subseqent human studies.

A few years ago, my mother was visiting us, and she was already in the early stages of cognitive decline. She took a sage supplement I had, and within hours she was much more like her previous feisty self. But subsequent bottles of the same sage brand of sage supplement did not have the same effect. Plain dried sage also failed to have a postive effect. I've been trying to figure out what could have been different about the first bottle; somewhere in its processing, the sage could have been exposed to yeast that altered it somehow, but in what way?

Quercetin-3-O-glucuronide has been found to be quite effective in treating Alzheimer's disease in a mouse model:

Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of Aβ1–40 and Aβ1–42 that is necessary for the formation of neurotoxic oligomeric Aβ species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.

Ho L, Ferruzzi MG, Janle EM, Wang J, Gong B, Chen TY, Lobo J, Cooper B, Wu QL, Talcott ST, Percival SS, Simon JE, Pasinetti GM. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J. 2013 Feb;27(2):769-81. doi: 10.1096/fj.12-212118.)

How can we get hold of some of that quercetin-3-O-glucuronide? Our liver makes glucuronide compounds via a process in the liver cells called glucuronidation. Ethanol, i.e., alcohol, triggers one of the pathways involved in glucuronidation of Tylenol (also known as acetaminophen or paracetamol), so perhaps getting Tylenol directly to the liver (i.e., not going through the stomach and intestines first) at the same time as quercetin can help the liver make some quercetin-3-O-glucuronide, too. 

Intravenous Tylenol doesn't seem to be a common part of most people's health regimens given how invasive it is to have an IV; I couldn't find any Tylenol skin patches for sale. There is a tantalizing study showing reduced delirium in older patients given IV Tylenol after a surgery (See Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, Gallagher J, Gasangwa D, Patxot M, Packiasabapathy S, Mathur P, Eikermann M, Talmor D, Marcantonio ER. Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):686-696. doi: 10.1001/jama.2019.0234. Erratum in: JAMA. 2019 Jul 16;322(3):276. PMID: 30778597; PMCID: PMC6439609.). 

What would happen if we gave people Tylenol intravenously via skin patches at the same time as they ate/drank lots of high-polyphenol fruits/vegetables/herbs? I think this is a possibility that should be looked at. Something is getting in the way of carrying over the results of rat/mice studies into humans when it comes to preventing age-related cognitive decline, and it think it might be a difference in human digestive systems versus the digestive systems of mice/rats.

Hypothesis: Hyaluronic acid in cosmetics and hair products are contributing to female infertility

It's interesting and a bit sad to look at what has been happening to fertility statistics in the USA. Women in their 20s are having far fewer babies now than they did 20 years ago. (See https://www.census.gov/content/dam/Census/library/stories/2022/04/fertility-rates-declined-for-younger-women-increased-for-older-women-figure-2.jpg.) No, it's not because they're less interested in having relationships or have greater access to birth control and abortions. While careers are certainly important to them, careers were important 20 years ago. Early abortion medicines are more available now than they were 20 years ago, so that could certainly be part of it, but effective contraceptive alternatives were numerous (and often given out free) 20 years ago. The dropoff in fertility seems to be more than just an increase in access to abortion. Many women in their 20s who want to have babies are having issues conceiving; that used to be quite rare, if I recall correctly. What could be happening?

I was recently learning about urinary tract infections and came across an interesting article on trigonitis (the trigone is a triangular piece of tissue in the lower part of the bladder), and it mentioned the efficacy of using sodium hyaluronate to help rebuild the surface of the trigone in order to heal trigonits. 

Sodium hyaluronate is a derivative of hyaluronic acid that replaces the deficient glycosaminoglycan (GAG) layer of the bladder wall. It is the traditional agent for GAG substitution therapy based on existing theories about urothelial dysfunction. Sodium hyaluronate has been safely administered with success for the treatment of chemical and radiation cystitis as well as interstitial cystitis.

Stavropoulos M, Papatsoris AG, Konstantinidis C, Chrisofos M. Pseudomembranous Trigonitis: A Common but Underrecognized Urological Entity. Adv Urol. 2010;2010:269254. doi: 10.1155/2010/269254. Epub 2010 Dec 1. PMCID:  PMC2997493. (online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997493)

Tight junction proteins are important in the tissue of the trigone compared to the rest of the bladder. (See Sánchez Freire V, Burkhard FC, Schmitz A, Kessler TM, Monastyrskaya K. Structural differences between the bladder dome and trigone revealed by mRNA expression analysis of cold-cut biopsies. BJU Int. 2011 Jul;108(2 Pt 2):E126-35. doi: 10.1111/j.1464-410X.2010.09934.x. Epub 2011 Jan 18. PMID: 21244608 (online at https://pubmed.ncbi.nlm.nih.gov/21244608)). 

Reduction of tight junction complexity in the uterus--which is right next to the bladder--can prevent blastocysts from implanting in the uterine surface and thus prevent a successful pregnancy. (See Mokhtar MH, Giribabu N, Salleh N. Testosterone Reduces Tight Junction Complexity and Down-regulates Expression of Claudin-4 and Occludin in the Endometrium in Ovariectomized, Sex-steroid Replacement Rats. In Vivo. 2020 Jan-Feb;34(1):225-231. doi: 10.21873/invivo.11764. PMID: 31882482; PMCID: PMC6984066 (online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984066))

If you've been paying attention to cosmetics and hair products in the past few decades, there has been a noticeable increase in the ones touting the inclusion of hyaluronic acid. Moreover, hyaluronic acid can also be present in ingredients such as keratin, hydrolyzed keratin, and the like.

Women, what if the sodium in our diets and in our bodies is sometimes combining with the hyaluronic acid in hair and cosmetic products to mess with the tight junction proteins in our uterine surfaces in ways that are contributing to female infertility? Is any hair look worth that result? A great adventure and joy of my life is being a mother, and I would hate to leave uninvestigated anything that could be preventing other women from enjoying the same privilege.