Wednesday, March 21, 2018

Dealing with acne: phosphatase enzymes (part 2)

My thirteen year old daughter has been trying topical application of UHT milk--for its alkaline phosphatase enzymes--on her face twice a day for just over a month now. (I explain why in part one of this series.) At the one-month mark, I checked the acne-prone areas of her face and found that her acne looked about bad as it had at the experiment's start a month earlier. That was weird, for her skin had been doing better several days before that.

I went to the refrigerator and smelled her liter of UHT milk, and it was quite sour. She'd been using the same liter container for a whole month. I did check it around the 3-week mark and it was still sweet then, but it soured since without her realizing it.

When milk goes sour, its pH decreases, meaning it becomes more acidic. (https://thedairydish.com/is-milk-acidic/) Alkaline phosphatases are so named because they have optimal activity when the pH is alkaline. Skin itself is acidic. (https://www.ncbi.nlm.nih.gov/pubmed/18489300) My daughter's sour milk applications thus probably didn't result in much alkaline phosphatase activity.

She is using a fresh liter of UHT milk now, and her face is doing better, too. I need to find a source of small UHT milk containers so that she can use a fresh one every week or so without it costing so much. Not that $1/liter is expensive, but it can add up if one has to open a new milk container every week or two.

Because skin is acidic, I also want to try acid phosphatase, which is optimally active at acidic pH levels. One source of acid phosphatases is wheat germ. (https://www.ncbi.nlm.nih.gov/pubmed/14408027) I can spend a lot of money to get a small amount of pure enzyme from a research supply company, or if I'm willing to accept impure enzymes, I can soak some wheat germ in cold distilled water, mix it gently, and then centrifuge it, using the liquid on top afterward. (http://www.sjsu.edu/people/peter.nemes/courses/Chem131A/s1/Acid-Phosphatase-Protocol.pdf) Guess which option I'll pick? I don't have a centrifuge yet, but I can make a "Dremelfuge" out of my husband's Dremel. (https://www.thingiverse.com/thing:1483)

However, I feel like I should give the UHT milk alkaline phosphatases a week or two more of trial time before changing the type of phosphatase we use. It's not the milk's fault that I didn't notice it had gone sour. When I do switch to wheat germ acid phosphatase, one thing I need to remember is not to mix the acid phosphatase with alcohol; ethanol inhibits acid phosphatase. (https://www.ncbi.nlm.nih.gov/pubmed/15762484)

Friday, March 9, 2018

Dealing with acne: phosphatase enzymes (part 1)

Almost two years ago, I was starting to worry about how to help my daughters with the inevitable onset of teenage acne and wrote about how manganese might be able to help: https://petticoatgovernment.blogspot.com/2016/07/skin-care-and-manganese.html. Now I have a thirteen year-old child, and she is dealing with some acne. It started to get quite bad up around her hairline. So she tried some lotion with some chelated manganese mixed in, but if the manganese helped her, it wasn't obvious that it did so. She also cut her milk consumption, since milk consumption is related to acne. (https://www.ncbi.nlm.nih.gov/pubmed/21335995) That did help a little, but she likes her morning glass of milk. And she likes peanut butter, which always tended to increase the number of pimples for me and my siblings. So I looked for recent research on what causes acne breakouts, and found that much has been discovered:
In the last years, a clear link between the endocrine signalling also influenced by Western diet and the pathogenesis of acne has emerged. In this context, a crucial role has been attributed to the hyperactivity of the conserved serine/threonine kinase mTORC1. mTOR is a nutrient-sensitive regulator of cellular growth, proliferation, lipid synthesis and protein translation, exerting its effects through two distinct signalling complexes: mTORC1 and mTORC2. In particular, the rapamycin-sensitive mTORC1 promotes cell growth and proliferation whereas mTORC2, rapamycin-non-sensitive, is involved in the regulation of cell polarity and in the functional phosphorylation of cytoskeleton actin fibres. mTORC1 is able to integrate multiple intra- and extracellular mediators such as growth factors (insulin, IGF-1) and energy-sensing signals (glucose, AMP/ATP-ratio), controlling the adequate availability of amino acids, especially the BCAA leucine, necessary for its own activation. Multiple diseases, either neoplastic, dysmetabolic or inflammatory, show dysregulation of mTOR pathway, which might be also involved in inflammatory skin diseases such as psoriasis, atopic dermatitis and allergic contact dermatitis. Enhanced levels of leucine [peanut butter is really high in leucine] and other amino acids, insulin, IGF-1 and glucose, deriving from meat, milk/dairy intake and high glycaemic load, permit mTORC1 activation through specific mechanisms. Consequently, by the phosphorylation of 4E-BP1, the lipin1 activator of SREBP-1 and S6K1, mTORC1 is able to enhance protein and lipid synthesis, as well as growth and cell proliferation. This could be translated into proliferation of acroinfundibular keratinocytes and increased lipid biosynthesis in sebaceous glands, responsible for seborrhoea. In two recent elegant papers, Melnik integrated mTORC1 signalling into the complex scenario of acne pathogenesis, highlighting the antagonistic interaction between the metabolic transcription factor FoxO1 and the nutrient-sensitive kinase mTORC1 . Nevertheless, either for the role of FoxO1 or for the modulation of mTOR in the pathophysiology of acne, direct evidences in humans are lacking.

"Mechanistic target of rapamycin (mTOR) expression is increased in acne patients' skin." Monfrecola G, et al. Experimental Dermatology 2016(25):153-155. online at http://onlinelibrary.wiley.com/doi/10.1111/exd.12885/full (references omitted).

In the Monfrecola publication, the researchers show that activated, i.e., phosphorylated S6K1 (P-S6K1), is more prevalent in the acne patient skin and is even more prevalent in the lesional skin than in the non-lesional skin. That points to the possibility that reversing the phosphorylation of S6K1 could decrease acne, which reversal could hypothetically be accomplished by topical application of phosphatase enzymes, for phosphatases remove phosphate groups.

Not being a funded research scientist, I looked around for inexpensive, readily available sources of phosphatase and came across just one: UHT milk. Milk has alkaline phosphatases (so named because they have optimal activity at alkaline pH) which are deactivated by pasteurization. However, the UHT process allows for subsequent reactivation of the alkaline phosphatases in the milk (https://www.ncbi.nlm.nih.gov/pubmed/988062https://helda.helsinki.fi/bitstream/handle/10138/41912/Ninios%20AI_Master%20thesis-1.pdf?sequence=1), and the longer the UHT milk sits around in its carton, the more active the enzymes become. The idea of using milk enzymes to promote clear skin has some historical backing for it: Cleopatra used to take milk baths, and for centuries milkmaids, despite high milk consumption, were praised for their complexions (some people think that was because of cowpox-caused immunity to smallpox, but that reason has apparently been debunked--http://www.jameslindlibrary.org/articles/the-origins-of-vaccination-no-inoculation-no-vaccination/).

I happened to have a liter of UHT milk in our pantry that was approximately a year past the "best by" date, so my teenage daughter and I are now doing an experiment with it to see if it helps her have less acne. On February 18, 2018, she started applying UHT milk to her hairline twice daily and all over her face once a day; she also stopped applying the lotion with manganese. This is what her hairline looked like:




Not terrible (although much of the skin damage is hidden by hair), but this was also taken when she was restricting her milk intake.

After a few days of the topical UHT milk treatment, she didn't have any new pimples forming, so I said she could drink as much milk and eat as much peanut butter as she wanted to. Then her father chimed in with concerns about whether she was washing her face enough, so I told her to use Cetaphil cleanser on her face every day. Unfortunately, she is not good at rinsing her face all the way off, and Cetaphil cleanser takes a lot of rinsing to remove completely. I think the Cetaphil residue blocked her pores, for she soon got pimples in places she hadn't had to worry about before, including one on the tip of her nose. So now she is washing her face with just water most days. Her hairline looks much better, but she is still dealing with pimples on other parts of her face. So yesterday, I instructed her to apply the UHT milk to her entire face twice daily. I hate to restrict her diet, but if the UHT milk phosphatases don't stop the acne, she will have to go back to restricting her milk intake. One thing we will not do is turn to coverup/foundation; if just Cetaphil residue can cause pimples in her skin, imagine what foundation would do to it!

I'll post follow-up pictures in a couple of weeks. She doesn't have cyclic eruptions, so if her skin is clear, then maybe we'll have found an easy intervention to save her from the teenage curse of acne. If not, it might be worth looking into what acid phosphatases are available; after all, skin pH is acidic, not alkaline.