Common Vitamin Could Be The Secret to Younger-Looking Skin
A new study has found that nourishment with vitamin C boosts epidermal thickness in lab-grown human skin models, and it does this by reactivating genes linked to cell growth. What's more, vitamin C concentrations normally delivered to human skin via the bloodstream are sufficient to have a measurable effect.
The research from Japan, first-authored by pharmaceutical scientist Yasunori Sato of Hokuriku University, points to vitamin C as a tool for staving off at least some of the impacts of aging on our largest organ.
"Vitamin C seems to influence the structure and function of epidermis, especially by controlling the growth of epidermal cells," explains biologist Akihito Ishigami of the Tokyo Metropolitan Institute for Geriatrics and Gerontology.
"We investigated whether it promotes cell proliferation and differentiation via epigenetic changes."
Related: 9 Foods That Pack More Vitamin C Than an Orange
Healthy human skin contains high levels of vitamin C, suggesting active accumulation, and concentrations are lower in aged or UV-damaged skin. We know that the vitamin plays an important role in skin health, boosting collagen production, alleviating UV damage, and providing antioxidant protection.
We also know that vitamin C plays a role in the demethylation of DNA, a process of removing methyl groups that is important for genetic stability and gene expression.
The addition or removal of methyl groups act like a kind of molecular switch that can turn gene activity on or off, without changing the genomic sequence.
What role demethylation plays in the differentiation of skin cells called keratinocytes, however, was unclear.
The human epidermis is dominated by keratinocytes, which form at the very bottommost layer and slowly move upward through its multiple layers as they mature, eventually becoming the dead cells that make up the skin's uppermost layer – the stratum corneum.
The stratum corneum consists entirely of dead cells, serving a protective function for the live skin cells underneath. It's from here that dead skin cells are shed, replenished by keratinocytes making their way up from below.
To test the role of vitamin C in skin health, the researchers grew human keratinocytes in petri dishes, with the upper layer exposed to the air, and fed by a nutrient solution from below, mimicking how skin behaves in living humans.
Into the nutrient solution, the researchers added concentrations of vitamin C consistent with the concentrations delivered by the circulatory system. A separate group of cells was grown without vitamin C as a control.
After one week, the models nourished with vitamin C had a thicker layer of living epidermis cells than the control group, while no effect was seen on the stratum corneum. After 14 days, the epidermal cell layer was thicker still, and the stratum corneum showed thinning, suggesting that the vitamin C was promoting cell proliferation.
Related:
The researchers sequenced the DNA and RNA of their samples, and traced this cell proliferation to demethylation that appears to be mediated by vitamin C sustaining the function of enzymes that regulate gene activity through demethylation.
These enzymes need a specific form of iron to keep doing their demethylation job, and vitamin C helps regenerate that form of iron. This effectively reactivates the genes associated with cell proliferation.
Under the influence of vitamin C, the expression of 12 key proliferation genes in the samples was increased, some by as much as 75 times.
When the researchers applied an inhibitor to the enzyme, the effect was reversed, confirming that vitamin C works through this specific pathway. These results suggest the vitamin may be useful to develop treatments for countering the effects of age.
"We found that vitamin C helps thicken the skin by encouraging keratinocyte proliferation through DNA demethylation," Ishigami says, "making it a promising treatment for thinning skin, especially in older adults."
The research has been published in the Journal of Investigative Dermatology.
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This transcript has been edited for clarity. Matthew F. Watto, MD: Welcome back to The Curbsiders . I'm Dr Matthew Frank Watto, here with my great friend and America's primary care physician, Dr Paul Nelson Williams. Paul, are thyroid nodules common? I heard they're not. Is that wrong? Paul N. Williams, MD: They're very common, Matt, and they actually become more common as we age. The reassuring thing is that most of them are benign and most of them are actually found incidentally. On the episode, we discussed how thyroid nodules are becoming even more common now that low-dose lung cancer screening is more prevalent. It's wonderful that the screening is more commonplace, but we're finding many incidental things, including thyroid nodules, on these scans. One nice thing to tell patients when we're starting the initial workup is that, by and large, these are extraordinarily common and they are usually benign — though not always, and we'll get to that in a little bit. Matt, if someone were to have a thyroid nodule, what kind of symptoms would you be asking the patient about? Watto: I would not have thought of this, but one of our guests, Dr Chindris, said that she asked people about neck tightness. That can be one of the symptoms that patients will have. She also asks about compressive symptoms, voice changes, and the classic hyperthyroid or hypothyroid symptoms (eg, heat intolerance, palpitations). Dr Chindris also mentioned that she had one patient who experienced a personality change and the family thought it might be related to the thyroid. This personality change did end up getting better once the patient had their hyperthyroidism treated. This might have been anecdotal, but I thought it was a cool anecdote. Take that for what you will, audience, but I guess personality changes could be on the list of symptoms as well. Williams: I guess it's one of the things that we always check when someone is feeling different or behaving sort of "off." So, maybe this validates that to some extent. Watto: But Paul, I'm going to be real with America here: I don't know that I've ever felt someone's thyroid and been able to absolutely, confidently state that they have a dominant nodule on a certain side of the neck. I'm good at noticing if someone's thyroid is so big that I can visibly notice it without even touching them, but thyroid nodules are difficult to feel. Tell us a little bit about that, Paul. You're the physical exam guy. Williams: If I remember the episode correctly, it turns out we miss about half of thyroid nodules on physical examination, even when they are over a centimeter. They're just tough and they're really hard to feel, especially if they're less than 1 centimeter. If they're located posteriorly, your chances are really sort of slim to none. These are not typically things that we find on examination. If they're large enough, I suppose that you could feel them, but don't beat yourself up. We also discussed the various techniques used for physical exams. When we were in medical school, the technique was to "stalk" the patient from behind and wrap your hands gently around their neck. You can also have the patient drink out of a straw. Watto: I think on the episode you asked, "So, how are we doing this? Are we still sneaking up behind them and choking them?" I like the approach that Dr Susan Mandel uses. She said she examines from the front, one side at a time, using her thumb. I think that's a good way to go. Williams: The one side at a time is clutch, for sure. Watto: And it's okay to give a patient a cup of water to have them swallow so you can feel the thyroid go up and down. I had stopped doing that for a little while — probably because of laziness; there aren't many cups in my office — but I think it's a good practice. Williams: Especially if you're feeling thyroids all day. Watto: Paul, the testing for this is pretty simple. Thyroid-stimulating hormone (TSH) is still going to be the workhorse here. Then, if you find a nodule, you're determining if it's a hot nodule or if the person could have Graves disease, depending on what you're seeing or feeling on exam. You don't necessarily have to get free T4 or T3 for every single person, but sometimes you can. We also asked about calcitonin because that had come up. There's not really a role for calcitonin anymore because if you are proceeding with fine-needle aspiration (FNA), they have these molecular tests that allow you to figure out which type of thyroid cancer it might be. So, it's just a pretty basic work workup. The TSH and then ultrasound can really shine here. Paul, have you ever ordered a radionuclide thyroid scan? Williams: No, I have not. I think I've seen it on certain algorithms and thought, Boy, if I'm thinking about ordering one of those, I should probably have the patient see endocrinology anyway, as is my way. I've never pulled the trigger on one myself, and I'm not even sure I've seen one ordered by endocrinology — at least not in the past 5 years, I don't think. Watto: Dr Chindris said she might order them sometimes, like in circumstances where you may be pre-oping a patient. But nowadays, even if someone is seeing an endocrinologist, they're not necessarily getting them. In primary care, if you're practicing on your own, you're probably not going to be ordering these too often. I don't think it's necessarily the wrong thing to do; you just don't have to do it. Williams: There are often easier ways to go about it, I think. Watto: And when you get the ultrasound report, it will have a TI-RADS — much like they have a BI-RADS for mammograms — and the higher the number, the worse it is. It goes from 1 to 5, with 5 being highly suspicious. If you do a FNA, you'll receive Bethesda categories which go from 1 to 6, with 6 being malignant and 1 being nondiagnostic. It's too much to get into on this video, but if you want to hear more, definitely check out the full episode where we talk through those. Paul, let's talk about GLP-1 agonists. Tell me if this is wrong, but I believe that everyone who's on a GLP-1 agonist should have yearly or twice-yearly thyroid ultrasounds, just as standard practice. Williams: That might be a bit overaggressive. Most people watching this probably know that if a patient has either a personal or family history of multiple endocrine neoplasia (MEN), that would be a contraindication for GLP-1 agonists. I think many of us have gotten a little bit squirrely in terms of thyroid cancer, in general. If there's a history of papillary thyroid cancer, we wonder, Ooh, is this still okay? When these agents were starting to be used, we probably looked it up every time and still had a little bit of trepidation about initiating GLP-1 agonist therapy. But our guests say they have plenty of patients with history of thyroid cancer — no, not medullary, but other differentiated types — who receive GLP-1 agonists, and our guests did not have any underlying concerns about this treatment. So, I don't know if we need to be doing serial ultrasounds. But Matt, I oftentimes feel like patients come to us and they may not know what specific type of thyroid cancer they have. Do you remember the party trick we can use to differentiate that? Watto: So, what you're saying, Paul, is that I don't have to routinely order a thyroid ultrasound if someone's on a GLP with agonist, but I should ask them if they have medullary thyroid cancer in their family or if they've had MEN2A. Then, if they're not sure what type of cancer they've had, you can ask them, "Have you been treated with radiation or thyroid suppression?" If they have been treated with either of those options, it's a good signal that they were probably treated for a well-differentiated thyroid cancer. You would not treat medullary thyroid cancer with radiation or suppressive doses of levothyroxine. That's a good way to figure out what type of thyroid cancer they have. In terms of anaplastic thyroid cancer, unfortunately it has such a poor prognosis that you're probably not going to be meeting someone 10 years down the line who doesn't remember which type they had. Those patients know if they had anaplastic thyroid cancer. So, the research and the party line right now would suggest it is safe to give GLP-1 agonists to patients who have had thyroid cancer or who have thyroid nodules. The only circumstance where GLP-1 agonists are not recommended is if they have medullary thyroid cancer or MEN2A. That's good news, Paul, because a lot of doctors out there are prescribing these for patients, and thyroid cancer is relatively common.
