deepresearch succeeded where o3 failed once again
Non-AGE Fluorophores in Skin Under UVA/Visible Excitation
Background: Skin Autofluorescence and AGE Reader Conditions
The DiagnOptics AGE Reader non-invasively measures skin autofluorescence (SAF) as a surrogate for advanced glycation end-products (AGEs). It uses near-UV to visible excitation (≈300–420 nm, peak ~370 nm) and detects emitted light in the 420–600 nm range (The AGE Reader, a Novel Tool for Noninvasive Cardiovascular Risk Assessment) (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
). SAF is reported as the ratio of emitted (420–600 nm) to reflected excitation light (The AGE Reader, a Novel Tool for Noninvasive Cardiovascular Risk Assessment). While fluorescent AGEs (e.g. pentosidine, exc ~335 nm/em ~385 nm) contribute to SAF (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
), many non-AGE compounds can also fluoresce under these conditions. This can confound SAF readings – especially in young, healthy individuals with low AGE levels but high levels of dietary or metabolic fluorophores. Below we dive into the chemistry of such compounds, focusing on phytochemicals and other endogenous fluorophores that emit under 300–420 nm excitation.
Endogenous Metabolic Fluorophores (Non-AGE)
Even without elevated AGEs, skin contains native molecules that fluoresce in the UVA–visible range:
-
Reduced NADH/NADPH: NADH (nicotinamide adenine dinucleotide, reduced form) is a fundamental metabolic cofactor that strongly autofluoresces. It has excitation bands ~320–380 nm and emission ~420–480 nm (
Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase - PMC
). NADH’s peak fluorescence occurs around 340 nm excitation yielding ~460 nm emission (NADH fluorescence - Bioblast). (Its oxidized form NAD^+ is not fluorescent.) High cellular NADH/NADPH (e.g. from active metabolism) can increase SAF. In fact, NADH is a known contributor to tissue autofluorescence (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
). Typical NADH concentrations in cells (hundreds of µM) mean its signal is significant.
-
Flavins (FAD/FMN and Riboflavin): Flavin adenine dinucleotide (FAD), an oxidative metabolism cofactor, fluoresces when oxidized. It absorbs broadly from ~350 up to 475 nm and emits green light roughly 480–600 nm (peak ~525 nm for free FAD (NADH and FAD kinetics reveal altered mitochondrial function in right …)). Riboflavin (vitamin B₂), the free flavin, similarly has an excitation maximum ~349 nm and emission ~532 nm (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). These flavins are naturally present (FAD in mitochondria, riboflavin in tissues/blood), and their fluorescence falls well within the AGE Reader’s detection band. For example, riboflavin’s greenish emission (around 532 nm) can add to background SAF (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). Flavin fluorescence is estimated to contribute ~20% of E. coli autofluorescence at 525 nm (Use of Flavin-Related Cellular Autofluorescence to Monitor …), highlighting its potency.
-
Intrinsic Proteins (Elastin & Collagen Crosslinks): Elastin, a structural protein in dermis and vessel walls, is highly autofluorescent. Its extensive conjugated cross-links (desmosine, etc.) cause blue-green fluorescence. Elastin has an excitation range ~350–450 nm and emission ~420–520 nm (A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS), perfectly overlapping the AGE Reader range. Collagen itself has native fluorescence mainly from pyridinoline cross-links and aromatic amino acids, but much of collagen’s emission is in near-UV (<420 nm) and thus minimally counted in SAF. However, enzymatic crosslinks like pyridinoline (in collagen) and oxidative crosslinks like dityrosine can emit around 400 nm, potentially adding some signal. In summary, structural proteins (especially elastin) can contribute substantial background autofluorescence (A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS) independent of AGEs.
-
Lipofuscin and Oxidation Byproducts: Lipofuscin, an age-related pigment (a complex of oxidized lipids/proteins), is highly fluorescent. It shows broad excitation 345–490 nm and emission ~460–670 nm (A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS). In older subjects, accumulated lipofuscin in skin could elevate SAF (emitting into the 460–600 nm window). Similarly, other advanced oxidation end-products (aldehyde adducts, etc.) form fluorescent chromophores (often termed ceroid pigments) with emissions in the blue-orange range. In a young person, these are low, but it’s worth noting that fluorescence is not exclusively due to glycation – oxidation products can mimic AGE signals.
-
Porphyrins: Porphyrin metabolites (from heme synthesis or skin microbiome) are natural fluorophores. For example, coproporphyrin III (produced by skin bacteria or gut) absorbs UV (~365 nm) and emits red light around 620 nm (Typical fluorescence spectra of coproporphyrin and protoporphyrin …). Protoporphyrin IX (heme precursor) has a Soret excitation ~405 nm and emission ~630–/700 nm. The AGE Reader’s detector (up to 600 nm) would catch the shorter portion of these emissions. In practice, porphyrin fluorescence is observed as a red/orange glow under UV (e.g. acne bacteria produce porphyrins that fluoresce orange). While typically low in amount, an unusual increase in porphyrins could slightly raise SAF readings on the red end.
-
Other Cofactors & Vitamins: Various vitamins can fluoresce. Notably, vitamin A (retinol) exhibits fluorescence (excitation ~335 nm, emission ~458 nm in serum) (A new, rapid fluorometric determination of retinol in serum - PubMed). Retinol and its esters are stored in skin; high vitamin A levels (e.g. from supplements) could therefore add a bluish fluorescence (~458 nm) to SAF. Vitamin B6 (pyridoxine/pyridoxal) is also intrinsically fluorescent, with typical excitation in the 320–350 nm range and emission ~400 nm ([PDF] Study on Fluorescence Spectra of B Vitamins Yang Hui - Atlantis Press). B6 is present as a coenzyme (pyridoxal-5-phosphate) in cells and may contribute a minor UV-blue autofluorescence. Finally, melanin, the skin pigment, has a broad fluorescence tail (excitation 340–400 nm, emission ~360–560 nm) (A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS). However, melanin’s effect is usually to absorb excitation light (reducing SAF) more than to emit light. In individuals with dark skin, melanin can dampen SAF (necessitating calibration) (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
), but any melanin fluorescence that does occur (broad greenish emission up to ~560 nm (A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS)) would register in the AGE Reader.
Dietary Phytochemicals and Exogenous Fluorophores
A high-vegetable diet introduces many fluorescent phytochemicals that can accumulate in skin or blood. These compounds often have conjugated ring structures or polyene chains that fluoresce under UVA/blue light. Key examples include:
-
Carotenoids: These pigmented antioxidants (β-carotene, lutein, lycopene, zeaxanthin, etc.) are abundant in fruits and vegetables and tend to deposit in human subcutaneous fat and skin (giving a yellow-orange hue in high intakes, as in carotenemia (Carotenemia - StatPearls - NCBI Bookshelf)). Carotenoids strongly absorb 400–500 nm light and can fluoresce in the green/orange. For instance, β-Carotene in solution shows emission around ~550 nm when excited in the 400–500 nm range (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). Lutein and zeaxanthin behave similarly (all have extensive conjugated double bonds). Notably, carotenoids have very low quantum yields (ϕ < 1e-4) (Beta-carotene - OMLC) – they fluoresce weakly compared to their absorption. Yet, if present at high concentration (99th percentile skin carotenoids), their cumulative emission can be detectable (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). In fact, fluorescence from carotenoids is observed in plant tissues (e.g. leaves show a 532 nm band attributed to β-carotene fluorescence) (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). In human skin, high carotenoid levels might similarly produce a small 500–600 nm fluorescence signal under UVA. This could explain anecdotally why placing a carotenoid-rich apple under the AGE Reader yielded a high reading – plant skins rich in carotenoids (and flavonoids) will autofluoresce under UV.
-
Polyphenols and Flavonoids: A wide array of polyphenolic compounds from diet are natural fluorophores (Glowing colours of foods: application of fluorescence and chemometrics in food studies | Spectroscopy Europe/World). These include flavonoids (e.g. quercetin, catechins), phenolic acids (caffeic/chlorogenic acid), and anthocyanins (berry pigments), among others. Polyphenols typically have one or more aromatic rings that absorb in the UV or blue range and emit in the blue-green. For example:
-
Quercetin (from apples, onions, etc.) has negligible free fluorescence, but when bound to proteins (like human serum albumin) it exhibits strong emission (peak ~524 nm with ~445 nm excitation in one study) (Fluorescence spectroscopy of quercetin in the absence and …). Thus, high plasma quercetin (from supplements or diet) bound in skin or blood could contribute to green fluorescence under ~370 nm excitation (Fluorescence spectroscopic evaluation of the interactions of …).
-
Resveratrol (3,5,4′-trihydroxystilbene, from red grapes) can be excited at 340–380 nm and emits a broad green fluorescence (~510 nm) (
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
). Researchers have observed resveratrol fluorescence at 510 nm under 360 nm light (
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
). Although resveratrol is rapidly metabolized to conjugates in vivo, high intake might yield transient fluorescence in tissues.
-
Curcumin (from turmeric) is a highly fluorescent polyphenol. It absorbs ~420 nm (bright yellow color) and emits 500–600 nm (appearing greenish fluorescence). In fact, curcumin’s fluorescence is so strong that mixtures of turmeric extract and pomegranate were shown to produce white-light emission under 380 nm excitation (White Light Emission from Vegetable Extracts | Scientific Reports). Curcumin is lipophilic and can accumulate in fatty tissues; a person consuming large amounts of turmeric could have curcumin in skin oils, giving a notable SAF signal (likely around 500–550 nm emission).
-
Anthocyanins (from berries, pomegranates, etc.) are colored flavonoids (red/blue pigments). In acidic form they absorb visible light (~500+ nm), but they also have an ultraviolet absorption band. Under UV excitation (~350–400 nm), anthocyanins can fluoresce in the orange-red range. Indeed, pomegranate polyphenols and anthocyanins were identified as key emitters (along with curcumin) in the 380 nm-excited white-light mixture, providing red and green components (White Light Emission from Vegetable Extracts | Scientific Reports). Thus, someone with a berry-rich diet might have circulating anthocyanins (or metabolites) that produce faint red-orange autofluorescence in tissues. (These emissions would be at the edge of the AGE Reader range, potentially up to ~600 nm.)
-
Catechins and flavanols (from green tea, cocoa) also exhibit fluorescence. For example, epigallocatechin gallate (EGCG) has aromatic rings that could emit blue light under UV. Polyphenols like these are water-soluble and don’t accumulate long-term, but frequent intake means they could be present in plasma or interstitial fluid at µM levels, contributing to SAF between meals.
-
Vitamins and Cofactors from Diet: Beyond riboflavin and carotenoids mentioned above, diet provides other fluorescent molecules. Thiamine (B₁) has UV fluorescence; pyridoxine (B₆) we noted (exc ~320 nm, em ~400 nm) ([PDF] Study on Fluorescence Spectra of B Vitamins Yang Hui - Atlantis Press); and folate (B₉) fluoresces (pteridine ring emission ~450 nm when excited ~360 nm). A robust intake of B-vitamins might slightly raise baseline autofluorescence. Chlorophyll from leafy greens is another noteworthy fluorophore – it absorbs UVA/blue and emits deep red (~~680 nm). While chlorophyll is usually broken down in digestion, any that incorporated or its metabolites (e.g. pheophytin) could, in principle, emit red fluorescence. (The AGE Reader mostly misses chlorophyll’s 680 nm peak, but its excitation could produce some far-red glow). Coumarins present in some plants (e.g. umbelliferone in carrots, parsley, citrus) have strong blue fluorescence (exc ~350 nm, em ~450 nm) and could be circulating in trace amounts. And even alkaloids like quinine (from tonic water) famously fluoresce blue (exc ~365, em ~450 nm) (Glowing colours of foods: application of fluorescence and chemometrics in food studies | Spectroscopy Europe/World) – though not a typical “health food”, a tonic water drink could briefly elevate skin fluorescence as quinine distributes.
Fluorophore (Source) |
Excitation λmax (nm) |
Emission λmax (nm) |
Presence in Skin/Blood |
**NADH / NADPH** (endogenous cofactor) |
340 nm (typical) |
460 nm (blue) ([
Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase - PMC
](https://pmc.ncbi.nlm.nih.gov/articles/PMC8367293/#:~:text=Reduced%20nicotinamide%20adenine%20dinucleotide%20,of%20exogenous%20labels%20or%20dyes)) |
High in all cells (hundreds of µM); contributes significantly to tissue autofluorescence ([
Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase - PMC
](https://pmc.ncbi.nlm.nih.gov/articles/PMC8367293/#:~:text=Reduced%20nicotinamide%20adenine%20dinucleotide%20,of%20exogenous%20labels%20or%20dyes)). |
**FAD / Flavins** (vitamin B₂, cofactor) |
370 nm & 450 nm (dual) *(broad 350–475 nm)* |
525 nm (green) ([NADH and FAD kinetics reveal altered mitochondrial function in right ...](https://academic.oup.com/eurheartj/article-abstract/34/suppl_1/P4199/2862336#:~:text=NADH%20and%20FAD%20kinetics%20reveal,recorded%20using%20an%20inverted)) *(480–600 nm range)* |
Present in cells (mitochondria) and plasma. Riboflavin from diet circulates (μg levels); skin stores small amounts. Strong green fluorescence ([Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)... | Download Scientific Diagram](https://www.researchgate.net/figure/Fluorescence-spectra-of-Aa-b-carotene-Ba-lycopene-and-Ca-norbixin-in-CH-2-Cl_fig1_266390079#:~:text=zeaxanthin%20%28Mandalari%20et%20al,)). |
**Elastin** (skin dermis protein) |
~360–400 nm |
460–500 nm (blue-green) ([A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS](https://evidentscientific.com/en/insights/a-biological-breakdown-of-autofluorescence-why-your-samples-naturally-glow#:~:text=whole%20tissues%20must%20be%20aware,1980)) |
Abundant in dermis and vessel walls. Crosslinks (desmosine) yield strong autofluorescence; baseline contributor to SAF ([A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS](https://evidentscientific.com/en/insights/a-biological-breakdown-of-autofluorescence-why-your-samples-naturally-glow#:~:text=whole%20tissues%20must%20be%20aware,1980)). |
**Lipofuscin** (aging pigment) |
360 nm / 488 nm (dual) |
610 nm (orange-red) ([Photodegradation of Lipofuscin in Suspension and in ARPE-19 ...](https://pmc.ncbi.nlm.nih.gov/articles/PMC8778276/#:~:text=,emission%20at%20610%20nm)) *(broad 460–670 nm)* ([A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS](https://evidentscientific.com/en/insights/a-biological-breakdown-of-autofluorescence-why-your-samples-naturally-glow#:~:text=become%20progressively%20more%20apparent%20as,Source%3A%20Billinton%20and%20Knight%202001)) |
Accumulates with age in cells (lysosomes). Minimal in young skin, but in older individuals can elevate SAF (broad emission into 600 nm) ([A Biological Breakdown of Autofluorescence: Why Your Samples Naturally Glow | Olympus LS](https://evidentscientific.com/en/insights/a-biological-breakdown-of-autofluorescence-why-your-samples-naturally-glow#:~:text=become%20progressively%20more%20apparent%20as,Source%3A%20Billinton%20and%20Knight%202001)). |
**β-Carotene** (carrots, etc.) |
450 nm (blue) ([Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)... | Download Scientific Diagram](https://www.researchgate.net/figure/Fluorescence-spectra-of-Aa-b-carotene-Ba-lycopene-and-Ca-norbixin-in-CH-2-Cl_fig1_266390079#:~:text=,)) *(~400–500 nm band)* |
~550 nm (green-orange) ([Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)... | Download Scientific Diagram](https://www.researchgate.net/figure/Fluorescence-spectra-of-Aa-b-carotene-Ba-lycopene-and-Ca-norbixin-in-CH-2-Cl_fig1_266390079#:~:text=zeaxanthin%20%28Mandalari%20et%20al,)) |
Lipid-soluble; accumulates in subcutis/skin (can reach > several μg/g in high intake). Very low quantum yield, but high skin levels can produce faint green-orange fluorescence ([Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)... | Download Scientific Diagram](https://www.researchgate.net/figure/Fluorescence-spectra-of-Aa-b-carotene-Ba-lycopene-and-Ca-norbixin-in-CH-2-Cl_fig1_266390079#:~:text=zeaxanthin%20%28Mandalari%20et%20al,)). |
**Lutein/Zeaxanthin** (leafy greens) |
440–475 nm (blue) |
~530–550 nm (green) |
Lipid-soluble; accumulate in skin and retina. Likely contribute minor green fluorescence in skin (similar to β-carotene) ([Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)... | Download Scientific Diagram](https://www.researchgate.net/figure/Fluorescence-spectra-of-Aa-b-carotene-Ba-lycopene-and-Ca-norbixin-in-CH-2-Cl_fig1_266390079#:~:text=zeaxanthin%20%28Mandalari%20et%20al,)). |
**Lycopene** (tomatoes) |
470 nm (blue) |
~600 nm (orange) |
Lipid-soluble; deposits in skin (gives reddish hue). Fluorescence is weak, but emission extends toward orange-red (some within 600 nm band). |
**Quercetin** (fruits/veg flavonoid) |
370 nm (in protein-bound form) ([Fluorescence emission spectra of quercetin in the presence of ...](https://www.researchgate.net/figure/Fig-4-Fluorescence-emission-spectra-of-quercetin-in-the-presence-of-various_fig3_234694967#:~:text=,ex%20%3D%20370%20nm)) |
524 nm (green, bound to albumin) ([Fluorescence spectroscopy of quercetin in the absence and ...](https://www.researchgate.net/figure/Fluorescence-spectroscopy-of-quercetin-in-the-absence-and-presence-of-CT-DNA-a-contour_fig2_317783955#:~:text=,However%2C)) |
Common dietary flavonoid; circulates bound to serum albumin. In skin, protein-bound quercetin could fluoresce green ([Fluorescence spectroscopic evaluation of the interactions of ...](https://www.sciencedirect.com/science/article/abs/pii/S0022231317309687#:~:text=,Considering%20the)). Free quercetin has minimal emission (quenched), but binding or glycosides may fluoresce. |
**Resveratrol** (grape/red wine polyphenol) |
340–380 nm (UV) ([
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
](https://pmc.ncbi.nlm.nih.gov/articles/PMC4960185/#:~:text=fluorescence%20in%20living%20cells%2C%20by,380%7D%20is%20the%20value)) |
510 nm (green) ([
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
](https://pmc.ncbi.nlm.nih.gov/articles/PMC4960185/#:~:text=fluorescence%20in%20living%20cells%2C%20by,380%7D%20is%20the%20value)) |
Low plasma levels unless supplemented. Transiently after wine or supplements, could appear in skin/blood and emit green light under UVA ([
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
](https://pmc.ncbi.nlm.nih.gov/articles/PMC4960185/#:~:text=fluorescence%20in%20living%20cells%2C%20by,380%7D%20is%20the%20value)). |
**Curcumin** (turmeric) |
420 nm (violet) |
~550 nm (yellow-green) |
Widely used spice/supplement; lipophilic and can bind membranes. Yields bright yellow-green fluorescence; can notably increase SAF if present on skin or in tissue (e.g. sweat, sebum). |
**Anthocyanins** (berries, pomegranate) |
350–400 nm (UV band) |
~600 nm (orange-red) |
Present in plasma after fruit intake (half-life hours). Fluorescence is pH-dependent; contributes red-edge emission under UV ([White Light Emission from Vegetable Extracts | Scientific Reports](https://www.nature.com/articles/srep11118#:~:text=the%20concentrations%20of%20the%20component,simple%2C%20cheap%20and%20fairly%20green)). Likely a small effect unless very high intake. |
**Porphyrins** (e.g. coproporphyrin) |
365–405 nm (UVA) ([Typical fluorescence spectra of coproporphyrin and protoporphyrin ...](https://www.researchgate.net/figure/Typical-fluorescence-spectra-of-coproporphyrin-and-protoporphyrin-IX-PpIX-produced-by_fig2_241435117#:~:text=Typical%20fluorescence%20spectra%20of%20coproporphyrin,10%2C%2011%5D%20.)) |
620–635 nm (red) ([Typical fluorescence spectra of coproporphyrin and protoporphyrin ...](https://www.researchgate.net/figure/Typical-fluorescence-spectra-of-coproporphyrin-and-protoporphyrin-IX-PpIX-produced-by_fig2_241435117#:~:text=Typical%20fluorescence%20spectra%20of%20coproporphyrin,10%2C%2011%5D%20.)) |
Produced by gut microbes or in heme pathway. Usually low in skin, but porphyrin buildup (or certain microbiome on skin) can cause red-orange fluorescence (e.g. acne). Partially detected up to 600 nm. |
**Vitamin A (Retinol)** |
330–350 nm (UV) ([A new, rapid fluorometric determination of retinol in serum - PubMed](https://pubmed.ncbi.nlm.nih.gov/1116915/#:~:text=PubMed%20pubmed,considerably%20more%20rapid%20than)) |
458 nm (blue) ([A new, rapid fluorometric determination of retinol in serum - PubMed](https://pubmed.ncbi.nlm.nih.gov/1116915/#:~:text=PubMed%20pubmed,considerably%20more%20rapid%20than)) |
Stored in skin as retinyl esters. High dietary or supplemental vitamin A could increase blue fluorescence in skin and serum ([A new, rapid fluorometric determination of retinol in serum - PubMed](https://pubmed.ncbi.nlm.nih.gov/1116915/#:~:text=PubMed%20pubmed,considerably%20more%20rapid%20than)). |
**Vitamin B6 (Pyridoxine)** |
320–335 nm (UV) ([[PDF] Study on Fluorescence Spectra of B Vitamins Yang Hui - Atlantis Press](https://www.atlantis-press.com/article/25854533.pdf#:~:text=Press%20www.atlantis,of%20vitamin%20mixed%20solution%2C)) |
400 nm (violet) ([[PDF] Study on Fluorescence Spectra of B Vitamins Yang Hui - Atlantis Press](https://www.atlantis-press.com/article/25854533.pdf#:~:text=Press%20www.atlantis,of%20vitamin%20mixed%20solution%2C)) |
Present as coenzyme (PLP) in cells. Emission mostly below 420 nm, so minor direct contribution to SAF, but could add to background excitation scatter. |
Table: Selected non-AGE fluorophores relevant to skin autofluorescence, with their approximate excitation and emission wavelengths and notes on their presence. Sources as indicated.
Influence on Skin Autofluorescence Measurements
Because the AGE Reader’s SAF score integrates all fluorescence from 420–600 nm, any of the above compounds can raise the reading independent of true AGE levels. In a person with a plant-rich diet and high antioxidant load, the skin may harbor unusually high levels of carotenoids and polyphenols (as in this case, 99th percentile carotenoids). These phytochemicals’ emissions (500–600 nm range) add to the detected signal, effectively mimicking an elevated AGE level. For example, one study noted that NADH, flavin, and porphyrin autofluorophores could influence SAF, although ~76% of SAF variance was explained by the AGE pentosidine (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
). Another analysis cautioned that “SAF may not only be caused by AGEs; other fluorophores such as keratin, vitamin D, lipofuscin, ceroid, NADH, and pyridoxine may add to the signal” (Skin color independent assessment of aging using skin …). Thus, in young subjects with low glycation but high nutrient levels, residual confounding fluorescence is indeed possible.
Notably, skin carotenoids are themselves a marker of a healthy diet and correlate with high plasma antioxidant vitamins (Carotenemia - StatPearls - NCBI Bookshelf) (Skin Carotenoids in Public Health and Nutricosmetics - MDPI). In one report, extremely high carotenoids caused technical issues in a skin Raman carotenoid scanner due to background fluorescence (Noninvasive assessment of dermal carotenoids as a biomarker of …). Likewise, a high SAF in a healthy young individual could be a false-positive “aging” signal caused by diet-derived fluorophores. It has been suggested that SAF devices should be interpreted with caution in such cases, as current algorithms assume fluorescence is primarily AGE-related.
Literature and Studies
While direct studies on diet-induced SAF elevation are limited, some relevant findings exist. Stirban et al. (2013) observed that acute glycemia changes didn’t fully explain SAF, hinting at other fluorophores (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
). Meerwaldt et al. (the AGE Reader validation) acknowledged that skin autofluorescence includes redox cofactors like NADH/FAD (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
). Researchers in food science have long noted that many nutrients are naturally fluorescent, including “aromatic amino acids, vitamins … and polyphenols” (Glowing colours of foods: application of fluorescence and chemometrics in food studies | Spectroscopy Europe/World). Fluorescence spectroscopy of foods shows carotenoids, chlorophylls, and phenolics all emitting in the 450–600 nm range (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram) (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram). By extension, when we “are what we eat,” our tissues can exhibit some of these optical properties.
There is growing interest in using skin fluorescence for nutritional status: e.g. devices like the VeggieMeter use reflection/fluorescence to gauge carotenoids in skin. Such devices must subtract background autofluorescence. In a large population study, skin carotenoid scores correlated with diet but also showed unexplained fluorescence variance in some individuals (Carotenoids in human skin - Lademann - 2011 - Wiley Online Library) – possibly due to differences in skin autofluorophores. Moreover, antioxidant supplements (β-carotene, etc.) have been reported to increase skin’s fluorescence under Wood’s lamp in dermatologic exams, supporting that diet can alter visible autofluorescence.
Conclusion
In summary, numerous non-AGE compounds can fluoresce under the AGE Reader’s 300–420 nm excitation, emitting light in the 420–600 nm band and potentially elevating SAF readings. These include endogenous metabolites like NADH and FAD, structural proteins like elastin, and diet-derived phytochemicals – notably carotenoids (emitting ~550 nm) and polyphenols such as curcumin, resveratrol, flavonoids (emitting 450–600 nm). The table above lists many such fluorophores, along with their spectral properties. A diet extremely high in vegetables can lead to high skin levels of carotenoids and other fluorophores, which confound AGE measurements by contributing to autofluorescence signals (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
) (Skin color independent assessment of aging using skin …). Therefore, when interpreting SAF results in health-conscious individuals, it is important to consider these chemical contributors. Future research and device algorithms may improve adjustments for these “good” fluorophores, ensuring that the glow of a nutritious diet is not mistaken for pathological AGE accumulation.
Sources: Peer-reviewed literature on skin autofluorescence and food chemistry, including device technical reports and biochemical studies (The AGE Reader, a Novel Tool for Noninvasive Cardiovascular Risk Assessment) (
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes - PMC
) (Fluorescence spectra of (A)(a) β-carotene, (B)(a) lycopene and (C)(a)… | Download Scientific Diagram) (
Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase - PMC
) (
Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations - PMC
), among others, as cited throughout.