Diet and Skin Wrinkles: Glycation, the Randle Cycle, and the Seed-Oil Question
Executive summary
No food, and no way of eating, stops ageing or removes wrinkles. The honest claim is narrower: some dietary patterns may lower specific biochemical processes that nudge skin toward wrinkling, and only ever alongside sleep, daylight, stress, movement and everything else you do.
Wrinkling is, in large part, the wearing out of the skin's structural proteins, collagen and elastin. Three mechanisms plausibly contribute: glycation (sugars cross-linking those proteins), chronic low-grade inflammation (to which fuel-selection biology may contribute), and, more speculatively, the oxidation of fragile polyunsaturated fats deposited in skin.
Glycation is the best-supported of the three. Reducing sugars react with collagen and elastin to form advanced glycation end-products (AGEs) that stiffen the tissue and resist normal repair (Ref 1, Ref 2). Much of the receptor-level detail (RAGE signalling) comes from cell and animal work and should be held loosely (Ref 3, Ref 4).
In observational data, higher blood glucose is associated with looking slightly older, on the order of a fraction of a year per unit of glucose, in part by way of wrinkling (Ref 7, Ref 8). That is an association, not proof of cause.
Chronically high sugar and insulin, and the forced fuel-selection described by the Randle cycle (Ref 9, Ref 10), plausibly feed the chronic, low-grade inflammation of ageing sometimes called "inflammaging", which is a recognised risk marker whose exact causal weight is still being worked out (Ref 11, Ref 12).
The seed-oil-and-sun idea is a hypothesis, not an established fact. Dietary linoleic acid is reflected in body fat (Ref 14), and ultraviolet light can oxidise polyunsaturated fats in skin (Ref 13), but no trial shows that eating fewer seed oils protects the face, and at least one skin-cell study found no measurable oxidation after short ultraviolet exposure (Ref 15). I am still collecting data here.
The practical message is a set of principles, not a magic shopping list: lower dietary carbohydrate as far as is sensible for you (Ref 19), reduce the excess industrial polyunsaturated load (my opinion, not settled fact), and avoid keeping sugar and insulin permanently elevated. None of it substitutes for sleep, daylight, movement and human connection.
Interest declared up front: I personally follow a low-carbohydrate, largely animal-based pattern of eating, so I hold a prior view that could bias me. I offer private consultations, but I sell none of the foods discussed here.
Introduction
The question this article asks is narrow and, I think, the only honest version of a popular one: does what you eat affect how your skin wrinkles, and if so, how much of that can we actually claim to know? The popular version, the one that sells, is "the foods that erase wrinkles". I have never been able to write that piece, because in the biology of ageing nothing works that way, and I would rather keep your trust than meet the demand.
Let me be clear at the outset about what I am and am not arguing, because this topic is easy to overstate in either direction. I am not claiming that any food, or the absence of any food, prevents wrinkles or reverses ageing. I am making a smaller and, I think, more defensible point: there are identifiable biochemical processes that contribute to the ageing of skin's structural proteins, diet plausibly modulates some of them, and the size of that contribution in any individual is something none of us can honestly quantify. Where the evidence is strong I will say so; where it is a mechanism I find persuasive but cannot prove, I will label it plainly as such.
A word on where I am coming from, in both senses. I trained first in dentistry, then in dermatology, and separately in anti-aging medicine and in metabolic medicine, and I have spent many years looking at the relationship between how people eat and how their skin and metabolism behave. I also owe you a declaration of interest that has nothing to do with money: I personally follow a low-carbohydrate, largely animal-based pattern of eating, and I already lean toward the view that stable, saturated animal fats are the safer default. That is a prior, and priors bias people, so please weigh what follows against it. I lean on biochemistry and mechanism more than on the messy human trials in this field, because the trials are so often confounded by uncontrolled diets and a dozen simultaneous lifestyle changes, but I hold that stance openly and I am genuinely willing to be moved by good contrary evidence.
The one mechanism worth understanding: what wears out the skin's springs
Most writing in this area hands you a list of foods. I would rather give you the single idea underneath the list, because once you have the mechanism you can reason for yourself.
Think of the dermis, the living layer beneath the surface of your skin, as a good mattress. What gives a mattress its bounce is the network of springs inside it. In skin, those springs are structural proteins, principally collagen and elastin, laid down and maintained by cells called fibroblasts. Young skin is springy because those proteins are intact and well organised. Aged, wrinkled skin is, in large part, what you get when the springs stiffen, tangle and lose the ability to repair themselves. So the useful question is not "which food is magic for my face"; it is "what wears the springs out". From a biochemical point of view there are three plausible culprits, and I will take them in descending order of how confident I am about each: sugar gumming the springs together, a low, smouldering fire of inflammation around them, and, most speculatively, fragile fats lodged in the springs and oxidising in the sun.
Glycation: sugar cross-linking the scaffolding
This is the most established of the three, and the least controversial, so it is the right place to start.
Glycation, in plain terms, is what happens when sugar in your blood reacts with your proteins without an enzyme telling it to. According to a review of the area retrieved via PubMed, glucose and fructose link the amino acids in the collagen and elastin that support the dermis and produce advanced glycation end-products, which carry the rather appropriate acronym AGEs; the process is accelerated when blood sugar is elevated and is further stimulated in skin by ultraviolet light (Ref 1). A helpful way to picture an AGE is as a tiny weld. Instead of a mattress of independent, bouncy springs, you get springs spot-welded to one another: stiffer, more brittle, and harder to service.
It is worth being precise about one thing here, because it is a point people often get wrong: glycation is not selective. It is a slow, non-enzymatic chemistry that will cross-link more or less any long-lived protein it can reach, which is exactly why collagen, one of the longest-lived proteins in the body, is such a frequent target. Nothing about the mechanism singles out skin, or singles out wrinkles; skin is simply where we can see the result.
Once formed, these welds are not easily undone. In work using mouse skin and modified collagen in the test tube, AGE-cross-linked collagen resisted the enzymes that would normally break down and recycle damaged collagen, so it accumulated (Ref 2). That is a plausible molecular reason why glycated tissue behaves like something that cannot be properly repaired, though I would flag clearly that this particular demonstration is in animal tissue and in vitro, and human skin may not behave identically.
There is a second arm to the story. Glycated proteins can bind a cell-surface receptor called RAGE (the receptor for AGEs), and that binding is described, in reviews retrieved via PubMed, as switching on oxidative and inflammatory signalling inside cells (Ref 3). The cleanest skin-specific version of this comes from experiments in cultured skin cells and animal skin, where ultraviolet exposure increased AGE-RAGE binding and, downstream, inflammatory signalling (Ref 4). I want to be upfront that this last part is largely cell-and-animal work, with added ultraviolet, rather than a demonstration in a living human face, so hold it loosely. The direction of travel is consistent, but the strength of the evidence is not the same as for the basic cross-linking.
A detail most accounts skip: not all sugars glycate at the same rate. In laboratory studies, fructose appears to be several times more reactive as a glycating agent than glucose, molecule for molecule, both in its early Maillard chemistry (Ref 5) and in its ability to cross-link collagen in the test tube (Ref 6). I would not oversell this. These are in-vitro findings, and, as ever, the honest caveat cuts the other way too: you carry far less fructose than glucose in your blood at any moment, so fructose being nastier per molecule does not straightforwardly mean it matters more in real life, because glucose is simply present in much larger amounts. The practical upshot for me is modest: I keep an eye on total sugar load rather than fixating on one sugar.
Does any of this actually show on a face? In the Leiden Longevity Study, higher non-fasted blood glucose was associated with a higher "perceived age" from facial photographs, by about 0.4 years for each 1 mmol/L increase in glucose among non-diabetic people, after adjustment for the obvious confounders (Ref 7). A later analysis from the same group found that a good part of that association ran specifically through skin wrinkling (Ref 8). I like these studies because they are a real-world echo of the mechanism, but I have to be honest about what they are: cross-sectional and observational, so they show association, not cause, and half a year of "perceived age" is a small effect.
This is also where I will gently point out an inconsistency in the usual "anti-wrinkle foods" lists, which tend to feature high-sugar items such as mango or dark chocolate. Judged as isolated ingredients those foods have real merits. But it is a little odd to hand someone a high-sugar fruit as an anti-wrinkle food in one breath while, in the next, agreeing that sugar drives the glycation that ages skin. I am not telling you mango is poison. I am saying the logic does not hold together, and now you can see why.
The honest bottom line on glycation is this. I cannot tell you what fraction of any given wrinkle was caused by sugar; there are far too many overlapping inputs for anyone to isolate that cleanly, and anyone who gives you a precise percentage is guessing. What is well supported is that glycation is real, that it stiffens and cross-links the skin's structural proteins, and that it is one genuine contributor among several.
Fuel selection, the Randle cycle, and inflammation
The second thing that plausibly wears out the springs is chronic inflammation, and this is where I get to describe a mechanism I find genuinely interesting, the glucose-fatty-acid cycle, usually called the Randle cycle.
The analogy makes it easy. Imagine a single engine that can run on either petrol or diesel, but not both flat out at once, because the two fuels share the same final set of parts. Your cells are a little like that. On the path from either fat or glucose down to ATP, the actual usable fuel currency a cell spends, there is a shared set of steps that cannot process both fuels at maximum at the same time. (When I say a cell "oxidises" a fuel, I mean the controlled, enzyme-run way it strips electrons out of that fuel to make ATP; nothing is literally on fire.) So a cell tends to be mostly running on one fuel or the other and to down-regulate its handling of the other. This competition was first described in 1963, in the paper that gave the cycle its name (Ref 9).
I should immediately add the cite-then-critique that intellectual honesty requires. The Randle cycle is a real and durable piece of physiology, but it is not the whole story of how fuels and insulin sensitivity interact. Later work makes clear that the accumulation of fat-derived signalling molecules inside muscle and liver, along with inflammation and oxidative stress, also drives changes in how cells respond to insulin (Ref 10). So the cycle is one lever, not the entire machine.
Here is why it may matter for your face. On a pattern of eating that keeps sugar and insulin chronically high, you keep pushing this fuel-selection system, and chronically elevated glucose and insulin are themselves a recognised driver of the low-grade inflammatory state described in metabolic disease, with raised interleukin-6, tumour necrosis factor-alpha and interleukin-1-beta (Ref 20). I want to be careful to label that as a mechanistic argument rather than a directly measured causal chain, because the leap from "the Randle cycle is chronically engaged" to "therefore the body is inflamed" is reasoning, not a single experiment I can point you to. What is better supported is the next link: chronic, low-grade, sterile inflammation is one of the genuinely accepted features of ageing, to the point that the field has a name for it, "inflammaging", and reviews describe how nutrient excess and overnutrition feed a closely related "metaflammation" (Ref 11).
And here the register of the evidence deserves precision, because the researchers themselves are careful. They describe inflammaging as a highly significant risk factor that sits alongside ageing, while stating plainly that its precise cause and its potential causal role in producing the damage remain largely unknown (Ref 12). So I would put my own position like this. That chronically high sugar and insulin are pro-inflammatory, I am reasonably confident about. That inflammation is bad for ageing tissue, including skin, is well supported. Exactly how much it ages your particular face, I cannot quantify, and it is probably a different amount in each of us.
I can hear the fair objections, and they deserve honest answers rather than to be waved away. One is that ectopic fat, fat stored in liver and muscle, is itself a cause of insulin resistance, so the arrow may point the other way. Another is the person who cuts carbohydrates and sees their fasting glucose rise, and concludes the whole picture is wrong. On that second point, a distinction matters: cutting carbohydrates can produce an adaptive, physiological insulin resistance, in which muscle preferentially spares glucose for the brain and its cells stop letting in glucose in response to insulin's signal, and this is not the same thing as the pathological insulin resistance of metabolic disease, even though a single fasting-glucose number cannot tell them apart. These objections are reasonable, and a proper treatment of each is longer than this article can carry; I raise them here so you know I am not pretending they do not exist.
One more thread ties this section to the last. When the human body does synthesise fat from surplus carbohydrate, the process (de novo lipogenesis) is stimulated by higher glucose and insulin, and its principal product is palmitate, a saturated fatty acid (Ref 17). I will come back to why that particular fact is quietly interesting.
Fragile fats and the sun: a hypothesis, clearly labelled
The third idea is the most speculative thing I will say, so I want a large, honest label on it before I begin. What follows is a hypothesis I find compelling, not a fact. I could be wrong, and I would be perfectly content to be shown so.
To follow it you need the difference between two kinds of fat. A saturated fat is a sturdy, stable molecule with no chemically weak points. An unsaturated fat, and especially a polyunsaturated one, contains one or more carbon-to-carbon double bonds, and each double bond is a fragile spot, a place that is comparatively easy to attack and oxidise. The kitchen version of this is familiar: saturated fats such as butter or tallow are solid and keep well, while polyunsaturated seed oils are liquid and eventually go rancid, and "rancid" is just a homely word for oxidised. Think of the double bond as a weak link in a chain: the more of them a fat carries, the easier the chain is to break.
The chain of the hypothesis runs as follows. First, the polyunsaturated fats you eat do not simply pass through; they are built into your tissues, and the amount of linoleic acid (the main dietary polyunsaturated fat) stored in body fat is used as a biomarker of long-term dietary intake precisely because intake is reflected in the tissue (Ref 14). Second, in skin, ultraviolet light can oxidise polyunsaturated fats, and a skin-focused review describes how this lipid oxidation generates reactive breakdown products that then form damaging adducts on collagen and elastin and contribute to the changes of photoageing (Ref 13). Third, the oxidised breakdown products of these fats are themselves biologically active and can be pro-inflammatory rather than inert (Ref 16). So the individual links are each plausible.
Now the honest counter-weight, because this is exactly the sort of tidy story that deserves suspicion. The review evidence above is largely mechanistic and drawn from cell and tissue models, not from a human face over years. More pointedly, at least one study exposing human skin cells to short bursts of ultraviolet A found the expected lipid oxidation did not appear, and reported no detrimental consequence over that window (Ref 15). And the biomarker paper that tells us dietary linoleic acid is reflected in body fat is the same kind of paper that, in a large cohort, found no association between that stored linoleic acid and heart attacks (Ref 14), which should caution anyone, myself included, against a simple "polyunsaturated fat is straightforwardly harmful" narrative. Above all, there is no trial showing that eating fewer seed oils gives you younger skin or protects your face from the sun. That experiment does not exist. So from here on this is observation and mechanism, not proof, and I am still collecting data.
What I can offer is an anecdote, clearly flagged as the weak evidence it is. In myself, in some of my patients, and in patients colleagues look after, a pattern keeps recurring: people who shift toward mostly animal-sourced saturated fats and cut the seed oils report that they stop burning in the sun the way they used to. It happened to me. I cannot lean on that, because someone who changes their diet usually changes ten other things at once, their sun habits, their weight, their sleep, so the anecdote is exactly the kind that can mislead, and I hold my own observations loosely. I mention it not as proof but because I cannot honestly pretend I have not seen it.
A necessary word on sunscreen, because this is where the wrong message is easy to take. I am not telling anyone to abandon sunscreen and go and bake. The thing that genuinely damages and ages skin is the burn itself. My own position is simply that, since changing how I eat, I personally burn less than I did and reach for sunscreen less than I once did. There is a much-quoted observation that skin cancer rates did not fall as neatly as expected after sunscreen became widespread, but I will not leave that hanging as a spooky mystery, because the honest reading is that the comparison is heavily confounded: people stay out longer when they feel protected, older formulations blocked the burning wavelengths while letting other ageing ones through, detection improved, and the heaviest sunscreen users are often those at highest risk to begin with. The honest summary is that the evidence here is not settled either way, so I treat my own experience as an experiment of one and nothing more. Please do not copy me on the strength of an article. If you are very fair-skinned, or you have ever had a skin cancer, do not take my personal experiment as your protocol; that is a conversation for you and a clinician who can actually examine you.
The Mediterranean question
All of this leads to a slightly heretical question, which I want to ask as a question rather than bang a drum about. Is the Mediterranean diet as unambiguously good for skin as we are usually told?
There are two honest problems. The first is definitional: what, precisely, is "the Mediterranean diet"? I have an office in Milan and spend a good deal of time there, and every Italian I meet eats differently; one has pasta daily, the next weekly. The label is far fuzzier than the confident headlines imply. The second problem is that some of the celebrated early data has real cracks. A commentary retrieved via PubMed points out that fieldwork behind the famous Cretan data overlapped with periods of Greek Orthodox fasting, when people were genuinely eating far less fat than usual, which would have made the everyday diet look leaner and healthier than it really was (Ref 18). I will cite it and then be fair about it: that commentary documents the fasting overlap itself; it is a strong reason for scepticism, not a full re-audit of the original study, and it is a short letter rather than a large re-analysis.
Set the population studies aside, though, because I find the biochemistry more persuasive anyway, and here is the quietly interesting fact I promised earlier. When the human body synthesises its own fat to store, the principal product is a saturated fatty acid, palmitate (Ref 17). Left to its own devices, the body builds the sturdy, stable molecule. So when I am told that a large glug of polyunsaturated oil is the single healthiest fat I can eat, I find myself asking, genuinely, whether that is as obvious as it sounds, given that saturated fat is what my own physiology chooses to make and store. I am not declaring olive oil bad, and I would not want that sentence quoted as if I had. I am inviting you to sit with the question, and I remain open to evidence in either direction.
What this looks like in practice
Now the practical part, and I am aware of a trap: I opened by gently mocking "five foods" lists, so the last thing I should do is hand you my own. Principles travel; lists do not.
The first principle is to lower dietary carbohydrate as far as is sensible for you. I will state one thing as physiology rather than opinion: there is no such thing as an essential carbohydrate. Your body can manufacture the glucose it needs from other substrates, which is why a published argument in the nutrition literature can reasonably ask whether dietary carbohydrate is required at all, in contrast to the essential amino acids and essential fatty acids that you genuinely must obtain from food (Ref 19). Fewer dietary carbohydrates means less of the sugar available to drive glycation, and steadier fuel that avoids constantly jamming the fuel-selection system described above. How far is "sensible" depends on you, and I cannot set that number through a screen.
The second principle, which I will flag clearly as my opinion rather than settled fact, is to reduce the excess industrial polyunsaturated load, chiefly refined seed oils. My reasoning is the evolutionary and biochemical one above, not a completed trial, and you should treat it as such.
The third principle is to avoid keeping sugar and insulin permanently elevated across the day, which is the same Randle idea applied to how you actually eat, and which lowers the smouldering inflammation that goes with chronic over-fuelling.
What does that look like as food? For me it is animal-sourced and simple: well-salted ruminant meat, fish, the natural fats that come with them, and unrefined salt. That is the core of how I eat. But I would rather you did not take it as gospel because I said it. There is genuine debate here, and you will find intelligent, qualified people who will tell you close to the opposite. Do not believe me, or anyone, merely because we have collected qualifications; go and understand the biochemistry, the physiology and the human history for yourself, and then decide.
I should also say plainly that I am not proposing you eat like this, joylessly, for the rest of your life. If a way of eating makes you miserable, that has its own costs. If the larger pattern is sound, a small, deliberate, occasional deviation you genuinely enjoy is not going to undo it. I follow this fairly strictly, roughly nine parts in ten, and the remaining tenth is modest and non-alcoholic in my case, an occasional Coca-Cola or some dessert. It is not individually "healthy", and I would not pretend otherwise, but in the context of an otherwise sound life it is a reasonable trade for enjoyment taken in sensible amounts. Where you draw that line is yours to decide.
On supplements, my rule is simply food first, with supplements reserved for specific situations rather than used as a default; I will not name products here.
And one human note, which is also where I will mention consultations, briefly. Knowing these principles is the easy part; living them around a real job, a real family and real tastes is the genuinely hard part, and if you find it difficult, that is not a personal failing. You do not need to see me for this. For most people a good, regular relationship with a local clinician is worth more than any single consultation with me, and there are many excellent clinicians who can help. I do offer private consultations for those who specifically want to work through their own situation with me, but I would rather you heard the humble version of that sentence than the salesy one.
Conclusion
Let me bring this back to where it started, honestly. I cannot promise you that eating this way will stop you getting wrinkles, and nobody being truthful can. What I can say is that you may be able to lower the specific biochemistry that pushes skin toward wrinkling: less glycation, less of the smouldering inflammation that accompanies chronically high sugar and insulin, and, if the seed-oil hypothesis holds up, fewer fragile fats sitting in the skin waiting to be oxidised. That is worth doing. It is not a magic trick, and I cannot tell you, for your face in particular, how much difference it will make, because I cannot see you through a screen and because the honest answer differs from person to person.
And keep the proportions right, because your face largely keeps the score of how you live. The best diet in the world will not rescue skin running on broken sleep, no daylight, chronic stress and no real human connection. Get those foundations in first, in whatever combination fits your life. Eat real food that is not spiking your insulin all day, get sensible daylight on your skin and eyes, sleep until you are genuinely rested, move, and stay close to the people you love. No plate and no product gets to skip those. Layer this biochemistry on top of them, and you have stacked the odds sensibly in your favour. That is about as honest as I can make it.
Disclosures
I sell none of the foods or supplements discussed in this article, and I have no financial interest in any of them. I do, however, hold a relevant non-financial bias that you should weigh: I personally follow a low-carbohydrate, largely animal-based pattern of eating, and I already lean toward stable animal fats as the safer default, so I am not a neutral observer of this evidence. I lean on mechanism and biochemistry more than on the confounded human trials in this field, and I have tried to flag every point where I am reasoning rather than citing a settled result. I offer private consultations for those who want to discuss their own situation, though for most people a good, regular relationship with a local clinician is worth more than any single consultation with me.
References
Identified and verified via PubMed; DOI links included.
Danby FW. Nutrition and aging skin: sugar and glycation. Clin Dermatol. 2010;28(4):409-411. https://doi.org/10.1016/j.clindermatol.2010.03.018 (Narrative review of glycation in skin ageing.)
Nowotny K, Grune T. Degradation of oxidized and glycoxidized collagen: role of collagen cross-linking. Arch Biochem Biophys. 2013;542:56-64. https://doi.org/10.1016/j.abb.2013.12.007 (Mouse skin and in-vitro collagen; AGE cross-linking resists degradation. Animal and in-vitro finding.)
Yamagishi S, Fukami K, Matsui T. Evaluation of tissue accumulation levels of advanced glycation end products by skin autofluorescence: a novel marker of vascular complications in high-risk patients for cardiovascular disease. Int J Cardiol. 2015;185:263-268. https://doi.org/10.1016/j.ijcard.2015.03.167 (Review; AGE-RAGE interaction and oxidative/inflammatory signalling.)
Oh S, Lee SY, Jang JW, Son KH, Byun K. Fermented fish collagen diminished photoaging-related collagen decrease by attenuating AGE-RAGE binding activity. Curr Issues Mol Biol. 2024;46(12):14351-14365. https://doi.org/10.3390/cimb46120860 (UV-irradiated keratinocytes and animal skin; AGE-RAGE binding drives inflammatory signalling. Cell and animal work.)
Dills WL. Protein fructosylation: fructose and the Maillard reaction. Am J Clin Nutr. 1993;58(5 Suppl):779S-787S. https://doi.org/10.1093/ajcn/58.5.779S (Review; early Maillard chemistry proceeds faster with fructose than glucose. In-vitro chemistry.)
Fujimori E. Cross-linking and fluorescence changes of collagen by glycation and oxidation. Biochim Biophys Acta. 1989;998(2):105-110. https://doi.org/10.1016/0167-4838(89)90260-4 (In-vitro rat-tail collagen; fructosylation more effective than glucosylation at cross-linking. In-vitro finding.)
Noordam R, Gunn DA, Tomlin CC, et al. High serum glucose levels are associated with a higher perceived age. Age (Dordr). 2013;35(1):189-195. https://doi.org/10.1007/s11357-011-9339-9 (Observational, cross-sectional; ~0.40 years higher perceived age per 1 mmol/L glucose in non-diabetic adults. Association, not causation.)
van Drielen K, Gunn DA, Noordam R, et al. Disentangling the effects of circulating IGF-1, glucose, and cortisol on features of perceived age. Age (Dordr). 2015;37(3):9771. https://doi.org/10.1007/s11357-015-9771-3 (Observational; higher glucose associated with higher perceived age, in part mediated by skin wrinkling.)
Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1(7285):785-789. https://doi.org/10.1016/s0140-6736(63)91500-9 (Original description of the Randle cycle.)
Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care. 2007;10(2):142-148. https://doi.org/10.1097/MCO.0b013e328042ba90 (Review; the Randle cycle is one mechanism among several for insulin resistance.)
Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576-590. https://doi.org/10.1038/s41574-018-0059-4 (Review; inflammaging and nutrient-driven metaflammation.)
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4-S9. https://doi.org/10.1093/gerona/glu057 (Review; inflammaging is a significant risk factor, but its causal role remains largely unknown.)
Negre-Salvayre A, Salvayre R. Post-translational modifications evoked by reactive carbonyl species in ultraviolet-A-exposed skin: implication in fibroblast senescence and skin photoaging. Antioxidants (Basel). 2022;11(11):2281. https://doi.org/10.3390/antiox11112281 (Review; UV-A drives polyunsaturated-fat oxidation and reactive carbonyl adducts on collagen and elastin. Largely mechanistic and in-vitro/ex-vivo.)
Nielsen MH, Frydenberg M, Bork CS, et al. Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study. Eur J Nutr. 2021;60(7):3639-3646. https://doi.org/10.1007/s00394-021-02526-y (Observational cohort; adipose linoleic acid is a biomarker of long-term dietary intake, but was not associated with myocardial infarction in this cohort.)
Leung KS, Chan HF, Leung HH, et al. Short-time UVA exposure to human keratinocytes instigated polyunsaturated fatty acid without inducing lipid peroxidation. Free Radic Res. 2017;51(3):269-280. https://doi.org/10.1080/10715762.2017.1300885 (In-vitro keratinocytes; short UVA exposure did not induce measurable lipid peroxidation. Counter-evidence.)
Mazzocchi A, De Cosmi V, Risé P, et al. Bioactive compounds in edible oils and their role in oxidative stress and inflammation. Front Physiol. 2021;12:659551. https://doi.org/10.3389/fphys.2021.659551 (Review; oxidised metabolites of dietary oils can be biologically active and pro-inflammatory.)
Smith GI, Shankaran M, Yoshino M, et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J Clin Invest. 2020;130(3):1453-1460. https://doi.org/10.1172/JCI134165 (Human clinical study; de novo lipogenesis yields palmitate, a saturated fat, and is stimulated by glucose and insulin.)
Sarri K, Kafatos A. The Seven Countries Study in Crete: olive oil, Mediterranean diet or fasting? Public Health Nutr. 2005;8(6):666. https://doi.org/10.1079/phn2005765 (Commentary/letter; Cretan fieldwork overlapped with Orthodox fasting, a confounder of the original diet picture.)
Westman EC. Is dietary carbohydrate essential for human nutrition? Am J Clin Nutr. 2002;75(5):951-953. https://doi.org/10.1093/ajcn/75.5.951 (Commentary/letter arguing there is no dietary requirement for carbohydrate, unlike essential amino acids and fatty acids.)
Silveira Rossi JL, Barbalho SM, Reverete de Araujo R, et al. Metabolic syndrome and cardiovascular diseases: going beyond traditional risk factors. Diabetes Metab Res Rev. 2021;38(3):e3502. https://doi.org/10.1002/dmrr.3502 (Review; chronic hyperglycaemia and hyperinsulinaemia drive metaflammation with raised IL-6, TNF-alpha and IL-1-beta.)
