IngredientsPhytofluene is a naturally occurring, colorless carotenoid of the carotene subclass. Its systematic chemical name is 7,8,11,12,7′,8′-hexahydro-ψ,ψ-carotene, reflecting its partially saturated polyene backbone. It is commonly abbreviated in the scientific literature as PTF or PF. Phytofluene, along with phytoene, is a precursor to all other carotenoids and is a rarity among carotenoids in that it has far fewer conjugated double bonds — specifically five — compared to most carotenoids, as a result of which it is colourless and possesses distinctive properties and actions.
Phytoene (PT) and phytofluene (PTF) are colorless carotenoids with differences in their chemical structure compared to other pigments; specifically, they have 9 and 10 double bonds, respectively. Of these double bonds, three are conjugated in phytoene and five in phytofluene, while other carotenoids are more unsaturated. Phytoene and phytofluene are rarities among carotenoids as they are colourless, have a less rigid conformation, and differ in their reactivity compared to other bioavailable carotenoids.
Phytoene is stepwise desaturated to form lycopene via phytofluene, ζ-carotene, and neurosporene by phytoene desaturase. Phytofluene therefore occupies the second position in the linear carotenoid biosynthetic chain, immediately after phytoene and immediately before ζ-carotene, making it an obligate biochemical intermediate in the production of lycopene, β-carotene, and all other downstream carotenoids. All carotenoids are derived from the colorless carotenes phytoene and phytofluene, which are oddities among carotenoids due to their distinct chemical structure.
The biosynthetic pathway involves 15-cis-phytoene being converted via 15-cis-phytofluene and 15-cis-ζ-carotene into all-trans-ζ-carotene and trans-bicyclic carotenoids. The phytoene is almost entirely the 15-cis isomer, and phytofluene is also present mainly as the 15-cis form.
Because phytofluene possesses only five conjugated double bonds, its light absorption falls in the ultraviolet range rather than in the visible spectrum, which explains its lack of color. Phytofluene exhibits UV absorption within the range of 260 to 320 nm. Dietary interventions of colourless carotenoids maximize the absorption of damaging light in the ultraviolet range, unlike coloured carotenoids that have maximum absorption in the visible range. This characteristic enables both phytoene and phytofluene to take very different forms, and such differences may influence their solubilization, stability, absorption, metabolism, and transport.
Phytofluene occurs together with lycopene in tomato and other lycopene-containing foods, and it is also present in frequently consumed products like oranges and carrots, among others. High contents of the colourless carotenoids are found in tomatoes, red grapefruits, watermelon (typically along with lycopene in these three cases), apricot, carrots, and some peppers. Other sources include cantaloupe, banana, melon, oranges, lemon, clementines, avocado, mandarin, nectarine, peach, and exotic fruits such as caja, buriti, mamey, marimari, physalis, and gac.
Quantitative data from population-level food studies confirm the widespread presence of phytofluene in everyday foods. The highest phytoene content was found in carrot, apricot, commercial tomato juice, and orange (7.3, 2.8, 2.0, and 1.1 mg/100 g, respectively). The highest phytofluene level was detected in carrots, commercial tomato sauce and canned tomato, apricot, and orange juice (1.7, 1.2, 1.0, 0.6, and 0.04 mg/100 g, respectively). Phytoene and phytofluene are mainly supplied by vegetables (81% and 69%, respectively). Considering the colour of the edible part of the foods analyzed, the major contributors to the daily intake of phytoene and phytofluene (about 98%) were of red/orange colour.
The intake of phytoene plus phytofluene has been shown to be higher than that of lycopene and other carotenoids in Luxembourg, and this is likely to be common in other countries. In a Spanish population study, the daily intakes of phytoene and phytofluene were 1.89 and 0.47 mg/person/day, respectively. The major contributors to the dietary intake of phytoene (98%) and phytofluene (73%) were: carrot, tomato, orange/orange juice, apricot, and watermelon.
Phytoene and phytofluene are major abundant dietary carotenoids that have been largely ignored in the context of agro-food and health. Several carotenoids can invariably be found in breast milk, human plasma, and various tissues including the skin, with significant carotenoids usually being α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, zeaxanthin, phytoene, and phytofluene.
In the context of dietary supplementation, phytofluene is not currently available in an isolated, highly purified single-compound form as a commodity ingredient. Instead, it is commercially supplied as part of multi-carotenoid tomato extracts and preparations. Formulations such as the Lycomato™ tomato extract, standardized to provide 15 mg lycopene per soft gel, contain additional fat-soluble natural tomato components including phytoene, phytofluene, natural tocopherols, beta carotene, and phytosterols. Specialized preparations standardized for high phytoene and phytofluene content have also been developed; one such product is PhytoflORAL®, a tomato powder rich in colorless carotenoids and poor in strongly colored carotenoids.
Phytoene is used as an ingredient in nutraceuticals as well as cosmetic products. Its use in formulations has several advantages over other carotenoids due to its stability, photo-insensitivity, and long shelf life. The same stability advantages apply to phytofluene. Both compounds are also being explored as ingredients in topical skincare formulations, and in vitro cytotoxicity and genotoxicity studies on phytoene- and phytofluene-rich tomato and Dunaliella salina alga extracts have revealed no significant cytotoxic or genotoxic potential, with short- and long-term human in vivo skin compatibility studies showing a lack of irritancy or sensitization reactions.
Phytofluene does not have a documented history of use as an identified, isolated compound within any traditional medical system. Being colorless and discovered through modern analytical chemistry rather than through sensory properties observable in traditional practice, it was not recognized or named as a distinct entity in pre-modern botanical or pharmacopeial literature.
Its traditional exposure was entirely dietary: the foods richest in phytofluene — tomatoes, carrots, apricots, and citrus fruits — have been consumed across Mediterranean, Middle Eastern, South American, and East Asian cultures for centuries and millennia. Tomatoes (Solanum lycopersicum), native to South America, were adopted into European and Mediterranean diets following the Columbian exchange. Carrots have been cultivated in Central Asia and the Mediterranean for over two thousand years, and apricots have been used in both Central Asian and traditional Chinese medicine contexts as food and as therapeutic preparations, though never with phytofluene specifically identified as an active constituent. Phytoene and phytofluene are major abundant dietary carotenoids largely ignored in the context of agro-food and health — reflecting the fact that their identification as distinct compounds is an achievement of 20th-century analytical chemistry rather than of traditional observation.
The scientific isolation and characterization of phytofluene as a discrete molecular entity belongs entirely to the modern era. These carotenoids are bioavailable and there are studies of diverse nature indicating that they could be beneficial for health; however, they have not been as extensively studied as the other major bioavailable carotenoids, namely lutein, zeaxanthin, β-cryptoxanthin, β-carotene and lycopene.
Phytofluene is a C40 acyclic hydrocarbon carotenoid (carotene) with the molecular formula reflecting its polyisoprenoid backbone. The acyclic carotenes phytoene and phytofluene are the precursors of all other carotenoids and are rarities in that they have a much smaller number of conjugated double bonds — three and five, respectively — compared to most carotenoids, as a result of which they are colourless and have distinctive properties and actions. The comparatively short conjugated system of phytofluene (five conjugated double bonds) distinguishes its reactivity from longer-conjugated carotenoids like lycopene (eleven conjugated double bonds) and β-carotene (nine conjugated double bonds).
The mechanisms by which carotenoids can be beneficial are not only antioxidant — there is also evidence that they can be prooxidants, enhance gap-junction cell communication, modulate gene expression, or absorb visible and even ultraviolet light (in the case of the colourless carotenoids phytoene and phytofluene). Phytofluene's antioxidant capacity is considered weaker than that of fully conjugated carotenoids such as lycopene, owing to its shorter conjugated double-bond system, but it remains a reactive oxygen species (ROS) scavenger in biological contexts. In addition to its role in skin health, phytofluene's distinct chemical structure and biological actions are attributed to antioxidant, anti-inflammatory, and anticancer activities.
A mechanistically important and chemically unique property of phytofluene among dietary carotenoids is its ability to absorb ultraviolet radiation. Both phytoene and phytofluene exhibit absorption maxima at wavelengths of UV light. The accumulation of these carotenoids in the skin increases their availability to exert their photoprotective effect on the surface during UV exposure. Their UV-absorbing, antioxidant, and anti-inflammatory attributes offer a global photoprotective effect. This UV absorption at biologically damaging wavelengths (within the UVB/UVA boundary region) provides a physical photofiltering mechanism distinct from the free-radical quenching associated with colored carotenoids.
Beyond their role as vitamin A precursors, carotenoids intervene in important biological actions that can contribute to reducing the risk of diverse diseases, including cancer, cardiovascular disease, skin, bone, eye, and metabolic disorders, and may be beneficial in relation to cognition and early development. For phytofluene specifically, in vitro and preclinical studies have examined effects including modulation of gene expression in keratinocytes and melanocytes. Clinical studies indicate that a cream containing 5% tomato colorless carotenoids significantly lightens skin by altering key gene expressions in keratinocytes-melanocytes co-cultures, highlighting their antioxidative and anti-inflammatory properties.
Although phytofluene and phytoene have been traditionally ignored, there is an expanding interest in them as recent studies indicate that they are present in widely consumed foods, are bioavailable, and may be involved in health-promoting biological actions. According to some reviews, associations between lycopene intake from tomato products and health should be revised to include other compounds present in tomato, including colourless carotenoids, because there are still obscure points in the possible health benefits of pure lycopene.
Lycopene, the red carotenoid found in tomatoes, is often considered to be the primary bioactive carotenoid in tomatoes that mediates health benefits, but other colorless precursor carotenoids, phytoene and phytofluene, are also present in substantial quantities. Phytoene and phytofluene are readily absorbed from tomato foods and tomato extracts by humans. Animal models of carotenoid absorption suggest preferential accumulation of phytoene and phytofluene in some tissues.
Bioaccessibility studies using simulated gastrointestinal digestion have demonstrated that phytofluene is among the most bioaccessible of dietary carotenoids. The bioaccessibility of phytoene and phytofluene in tomato, carrot, blood orange (sanguinello cultivar), and apricot juices was analysed following simulated gastro-intestinal digestion with coffee cream as a lipid source. The bioaccessibility of phytoene and phytofluene, and also total carotenoid bioaccessibility, followed the order: sanguinello > apricot > tomato > carrot. Phytoene was consistently the carotenoid with the highest bioaccessibility, up to 97%, generally followed by phytofluene. The higher bioaccessibility of these carotenoids could mainly be due to their marked difference in chemical structure and matrix distribution. For most juices, cis-isomers presented a higher bioaccessibility than their all-trans counterparts.
The reasonably high concentrations of phytoene and phytofluene detected in serum and tissues relative to the concentrations in foods suggest that absorption or metabolism of these compounds may be different from that of lycopene. Phytofluene and phytoene exhibit a slightly different distribution pattern in human plasma lipoproteins than do the other hydrocarbon carotenes.
In a key preclinical study, researchers hypothesized that phytoene and phytofluene are bioavailable from a tomato powder diet or from a purified source and accumulate in androgen-sensitive tissues. In that study, male Fisher 344 rats were fed an AIN-93G powder diet composed of 10% tomato powder containing phytoene, phytofluene, and lycopene (0.015, 0.012, and 0.011 g/kg diet, respectively). After 30-day tomato powder feeding, hepatic phytofluene concentrations (168 ± 20 nmol/g) were higher than phytoene or lycopene (104 ± 13 and 104 ± 13 nmol/g, respectively).
An important observation is that the carotenoid profile of the food or dietary supplement does not adequately predict relative plasma or tissue amounts of carotenoids. The reasonably high concentrations of phytoene and phytofluene detected in serum and tissues relative to the concentrations in foods suggest that absorption or metabolism of these compounds may be different from that of lycopene. Experimental studies, both in vitro and in vivo, suggest that phytoene and phytofluene exhibit bioactivity but little is known about their impact in humans.
The body can absorb phytoene and phytofluene well and they are found in the blood and several tissues. However, because they are colourless they have been called rare carotenoids, and research in the context of innovative product development, agro-food, nutrition, and health has been largely overlooked. Phytoene and phytofluene can be absorbed from the diet, and plasma concentrations increase after consuming tomato products.
The interindividual variability in phytofluene bioavailability has been found to have a genetic basis: research published in 2022 in Molecular Nutrition & Food Research demonstrated that the interindividual variability of phytofluene bioavailability is associated with a combination of single nucleotide polymorphisms.
The most clinically studied application of phytofluene (typically studied alongside phytoene) is the dietary protection of skin against ultraviolet radiation. This research area has produced both controlled clinical trial data and mechanistic supporting evidence.
A landmark study published in the International Journal for Vitamin and Nutrition Research (Aust et al., 2005) investigated the photoprotective effects of three forms of lycopene supplementation. Investigators compared synthetic lycopene against Lyc-o-Mato® (a tomato extract) and a drink containing solubilized Lyc-o-Mato®, with volunteers ingesting similar amounts of lycopene (about 10 mg/day). After 12 weeks of supplementation, significant increases in lycopene serum levels and total skin carotenoids were observed in all groups. Significant increases in the serum levels of phytofluene and phytoene occurred in the Lyc-o-Mato and the Lyc-o-Guard-Drink groups. A decrease in the erythema index from week 0 to week 12, indicating prevention of erythema formation, was observed in all groups. Compared to week 0, the erythema index at week 12 was 25% lower in the synthetic lycopene group. The protective effect was more pronounced in the Lyc-o-Mato (38%) and Lyc-o-Guard-Drink (48%) groups, and in the two latter groups, phytofluene and phytoene may have contributed to protection. Both carotenoids exhibit absorption maxima at wavelengths of UV light, and absorption of UV light protects skin from photodamage and might explain the differences observed between groups.
A larger, double-blind, randomized, placebo-controlled multicenter trial (the Tomato Nutrient Complex study) subsequently examined this question with greater rigor. This study analyzed whether a synergistic carotenoid-rich tomato nutrient complex (TNC) could protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlated with carotenoid blood levels. One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene combined, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day, or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken.
A preliminary open-label clinical study focused specifically on a tomato powder rich in phytoene and phytofluene (PhytoflORAL®) documented that a food supplement containing a tomato powder rich in phytoene and phytofluene, the colorless carotenoids, presented a significant photoprotective effect after 84 days of product use, as observed in a significant increase of the minimum erythemal dose (MED) by, on average, 10%. The effect was noticeable in 65% of subjects who saw their MED value increase by 20%; clinically, significant improvements in skin dryness, roughness, suppleness, evenness, and texture were also recorded, with subjective evaluations confirming improvement in skin radiance, evenness, hydration, smoothness, suppleness, elasticity, and irritability. The intervention was globally well tolerated with no relevant cutaneous side effects. This study was open-label, small, and lacked a placebo comparator, substantially limiting the strength of its conclusions.
Recent works showed that the intake of 5 mg of phytoene and phytofluene per day from tomato powder for 3 months resulted in a 20% increase in the MED. However, because phytofluene is invariably co-administered with phytoene and often with lycopene in these preparations, it is not possible from current human studies to isolate the specific contribution of phytofluene alone to these outcomes. The evidence for dietary photoprotection by tomato carotenoid complexes containing phytofluene is preliminary to moderate in strength, limited by small sample sizes, open-label designs in some cases, and the use of multi-ingredient products.
A 12-week intervention with a freeze-dried natural tomato powder food supplement led to improvements in a series of skin quality parameters, including skin radiance, suppleness, evenness, smoothness, moisturization, elasticity, visible skin health, visible skin youthfulness, and overall skin beauty, both clinically assessed and self-perceived by the volunteers.
A 2023 open-label clinical study enrolled 56 female participants (50 completers) aged 35–55 years. The Lycomato™ soft gels, standardized to provide 15 mg lycopene, contain additional fat-soluble natural tomato components such as phytoene, phytofluene, natural tocopherols, beta carotene, and phytosterols. Subjects were instructed to swallow them once a day for 12 weeks. This was an open-label study, with both the study team and the participant knowing what product they received. As with the photoprotection studies, these skin appearance results reflect the effect of multi-carotenoid tomato extracts rather than isolated phytofluene.
Phytoene and phytofluene, natural colorless carotenoids, have shown potential as safe and effective agents for skin lightening, especially in treating dark spots and uneven skin tone. Clinical studies indicate that a cream containing 5% tomato colorless carotenoids significantly lightens skin by altering key gene expressions in keratinocytes-melanocytes co-cultures, highlighting their antioxidative and anti-inflammatory properties. These colorless carotenoids could also participate in biological actions leading to cosmetic benefits. Evidence in the skin appearance domain is currently rated as preliminary; existing human data are confounded by multi-ingredient formulas and predominantly unblinded study designs.
Epidemiological studies suggest an inverse relationship between tomato consumption and serum and tissue lycopene levels with risk of some chronic diseases, including several cancers and cardiovascular disease. Tomato product consumption is inversely related to prostate cancer incidence, and lycopene has been implicated in reduced prostate cancer risk. However, the contribution of other tomato carotenoids — phytoene and phytofluene — toward prostate cancer risk has not been adequately studied. Short-term clinical studies on patients with prostate cancer have reported on tomato carotenoid distribution.
Preclinical data in rodents established that after 30 days of tomato powder feeding, hepatic phytofluene concentrations (168 ± 20 nmol/g) were higher than phytoene or lycopene (104 ± 13 and 104 ± 13 nmol/g, respectively), suggesting preferential hepatic accumulation. Whether this tissue distribution translates into chemopreventive effects in humans remains undemonstrated. Epidemiological evidence suggests an association of the colourless carotenoids, phytoene and phytofluene, with positive health effects by reducing the risk of various chronic diseases. However, no controlled human trials have yet isolated and tested phytofluene alone for cancer outcomes. The cancer-related evidence for phytofluene specifically remains at the preclinical and epidemiological-association level only.
Research attention has been focused on the colourless UV radiation-absorbing dietary carotenoids phytoene and phytofluene, which are attracting increased interest in food science and technology, nutrition, health, and cosmetics. These compounds are major dietary carotenoids, readily bioavailable, and have been shown to be involved in several health-promoting actions. The proposed mechanisms include free-radical scavenging, enhancement of gap junction intercellular communication (GJIC), and modulation of inflammatory signaling pathways. Their distinct chemical structures and biological actions are attributed to antioxidant, anti-inflammatory, and anticancer activities. No large, blinded, adequately powered human clinical trials have specifically assessed phytofluene as a stand-alone antioxidant or anti-inflammatory supplement, and evidence for these effects in humans remains largely indirect, extrapolated from tomato product intervention studies, or derived from in vitro and animal experiments.
Carotenoids intervene in important biological actions that can contribute to reducing the risk of diverse diseases, including cardiovascular disease. The epidemiological association between higher tomato carotenoid intake and reduced cardiovascular risk is documented, but again, it is confounded by lycopene and other co-occurring phytonutrients. Specific mechanistic and human clinical evidence isolating phytofluene's cardiovascular effects is currently absent from the peer-reviewed literature. Evidence in this domain is rated as preliminary or absent.
Because phytofluene in human studies has invariably been administered as part of multi-carotenoid tomato preparations rather than as an isolated compound, reported dosages reflect the phytofluene content within those formulations. The following figures appear in the peer-reviewed literature:
No universally established or regulatory-approved therapeutic dosage for phytofluene has been defined. All dosages described in the literature are those used in specific study protocols and should not be interpreted as recommended intake levels.
The colorless carotenoids phytoene and phytofluene are comparatively understudied compounds found in common foods such as tomatoes and in human plasma, internal tissues, and skin. Being naturally present in common foods, their intake at dietary levels is not expected to present a safety concern.
Formal toxicological evaluation of phytofluene-rich extracts has been conducted, though data remain limited. In vitro cytotoxicity and genotoxicity studies revealed no significant cytotoxic or genotoxic potential, and short- and long-term human in vivo skin compatibility studies with phytoene- and phytofluene-rich tomato and Dunaliella salina alga extracts showed a lack of irritancy or sensitization reactions. These results support the safe use of phytoene- and phytofluene-rich products in human topical applications.
Several tomato products have been categorized as GRAS (Generally Recognized as Safe) by the FDA, including tomato pulp powder or concentrated tomato lycopene extract. Similarly, EFSA considers colourless carotenoid-containing tomato oleoresins safe for human consumption. Phytofluene is not listed separately under any current regulatory framework as a novel food ingredient requiring pre-market authorization, as it occurs naturally within tomato products that have established safety profiles.
Carotenoids or carotenoid-containing products are categorized as GRAS by the US FDA. EFSA has established acceptable daily intakes (ADIs) of 0.5 and 1 mg/kg body weight/day for the common dietary carotenoids lycopene and lutein, respectively. This means that daily intakes of 30 and 60 mg of such carotenoids by a person of 60 kg are not considered of safety concern. No equivalent ADI has yet been formally established by EFSA specifically for phytofluene as an isolated compound.
Unlike β-carotene and lycopene, which impart yellow-orange or red pigmentation to the skin at high intake levels (a benign condition called carotenodermia), phytofluene's lack of visible-spectrum chromophore means it does not contribute to skin discoloration regardless of intake level. This represents a meaningful safety advantage in the context of nutricosmetic supplementation.
No specific pharmacokinetic or pharmacodynamic drug interactions for phytofluene have been identified in the peer-reviewed literature to date. Carotenoids are natural compounds widespread in foods that are naturally present in the diet and can be used as additives or ingredients of supplements; they are present in human plasma and tissues. As lipophilic compounds, phytofluene and related carotenoids are absorbed via the same lipid-micellarization pathway as dietary fats and fat-soluble vitamins; very low-fat diets or conditions causing fat malabsorption (e.g., cholestasis, cystic fibrosis, short bowel syndrome) may theoretically reduce their absorption, consistent with carotenoid class behavior. No interaction studies specific to phytofluene and pharmaceutical drugs are available.
Mostly due to their lack of color, phytoene and phytofluene have been largely overlooked in studies dealing with carotenoids in the context of agro-food, nutrition and health as well as in the development of innovative products. Experimental studies, both in vitro and in vivo, suggest that phytoene and phytofluene exhibit bioactivity, but little is known about their impact in humans. The following key research gaps persist in the phytofluene literature:
Health conditions that Phytofluene may help support.
Body systems that Phytofluene may help support.
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