- Email: [email protected]
Canthaxanthin in aquafeed applications: is there any risk?
Trends in Food Science & Technology 12 (2002) 240–243
Viewpoint
Canthaxanthin in aquafeed applications: is there any risk? Re´mi T.M. Baker BASF AG, 67056 Ludwigshafen, Germany (e-mail: [email protected])
The carotenoid pigment ‘canthaxanthin’ has been used in aquafeed for many years in order to impart the desired flesh colour in farmed salmonids. A side effect of extreme overdosage of this carotenoid is the deposition of minute crystals in the eye, a fact leading to adverse media attention for canthaxanthin in the past, and some pressure to limit its use aquafeeds. A real appraisal of the possible amount of canthaxanthin ingested by humans through the consumption of notable quantities of highly pigmented salmon, reveals that it is extremely unlikely that consumers could be exposed to sufficient canthaxanthin to attain the established ADI for this pigment. Additionally, the ADI is 10 times lower than the reported no-effect level (NOEL) for canthaxanthin. Therefore, canthaxanthin is a safe source of carotenoids for salmonid feeds. # 2001 Elsevier Science Ltd. All rights reserved.
In marine ecosystems, canthaxanthin is found in algae, bacteria and in crustacea, but subsequently accumulated in fish upon consumption of prey items. With aquaculture, it has been possible to enrich the flesh of species such as salmon with canthaxanthin, by utilizing commercial preparations of this pigment in the manufacture of pelleted feeds. This is possible because fish have the capability to transport and deposit this pigment at specific sites in their muscle, just like the canthaxanthin molecules encountered in the wild. The motivation for increasing flesh levels of carotenoids is that without them, flesh from trout and salmon would be less visually attractive, and therefore would be less valued as a seafood. After all, who can deny the appeal of richly coloured smoked salmon for example? Without dietary supplementation of these pigments, the aquaculture industry would find it hard to support the production of salmonid species because fish demand is driven through consumer demand for quality products. Bear in mind that the consumption of salmonid flesh is a great contributor to the intake of n-3 fatty acids in humans, and thus has the potential to supply important nutritional factors for human health (Torres, Mira, Ornelas, & Melim, 2000). Much research indicates that intake of fish should be increased in order to improve resistance to coronary heart disease for example. In many of the mature retail markets, affordable, attractive salmon is key to these health drives. Astaxanthin is very well accepted as a feed pigment, but historically, canthaxanthin abuse in sunless tanning applications has led to some resistance against the widespread use of canthaxanthin. Is there a real risk to canthaxanthin’s use in fish feeds?
Flesh deposition of canthaxanthin Introduction For many years now, astaxanthin has been the main flesh-colouring pigment of choice in a bulk of the trout and salmon farming industries. Synthesized formulations of canthaxanthin have also been very successfully applied with similar results to those obtained with astaxanthin. Both astaxanthin and canthaxanthin are found in nature, where they play important roles in animal displays of maturity and in the protection of tissues (plant and animal) against oxidising free radicals (Møller et al., 2000).
Many studies have demonstrated that astaxanthin is more efficiently deposited than canthaxanthin in rainbow trout (Storebakken & Choubert, 1991; Torrissen, 1986). The same is not true of Atlantic salmon as has been highlighted by Baker et al. (in press), the work of Buttle, Crampton, and Williams (2001) and in numerous unpublished commercial-scale trials. The difference may be due to genetic background and/or environment, although it has been previously shown that salinity is not a factor accounting for the difference (Baker et al.). Wide-scale application of canthaxanthin in rainbow trout feeds is unlikely. In Atlantic salmon pigmentation,
0924-2244/02/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S 0 92 4 - 2 24 4 ( 0 1 ) 0 0 09 1 - 7
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
however, canthaxanthin has been widely used in Britain, Canada and more recently Chile (pers. obs.), in some cases, 100% of the feed pigment coming from this one source. Feed levels of pigment vary from one fish producer to the next, depending on feed regulations, intended market, and producer-designed feeding regimes. These feeding regimes are designed to get the salmon to an intended colour target as cost efficiently as possible without incurring risks of under-pigmentation. Whilst some producers favour an early high start-dose, decreasing as the fish gets closer to harvest, others opt for a late starting regime. A moderate flat-dose is also commonly used. Feed supplementation levels for canthaxanthin tend to range between 40 and 80 mg/kg, similar to the doses normally applied for astaxanthin. Whatever the regime employed, the canthaxanthin content of flesh from 4 kg harvested salmon fed aquafeed dosed with commercial canthaxanthin preparations usually lies within the range 6–10 mg canthaxanthin per kg flesh.
Human intake of canthaxanthin from salmon Taking the figures shown above, and assuming that a typical portion of fresh salmon for consumers is 100– 200 g, this equates to a range of human canthaxanthin intake of between 0.6 and 2.0 mg for that portion. A weekly normal figure for the consumption of salmon is hard to define given the differences between countries. Because of associated n-3 fatty acid intake, many nutritionists advise that 2–3 portions of oily fish (such as salmon) would be beneficial in a balanced diet. The Food Standards Agency (2001) have more recently advised that at least one portion of oily fish should be consumed per week. Assuming that three portions of salmon are in fact consumed, that highly pigmented salmon is taken, and that a portion is 150 g, the weekly intake of canthaxanthin would be 4.5 mg (0.64 mg/day). This is on the extreme side already, as this would represent an annual salmon intake of 23.4 kg. As a comparison, the total per capita seafood consumption in France (fish and substantial amounts of shellfish) in 1997 was estimated at 27.5 kg (World Resources Institute internet page). Nevertheless, using these generous estimates, Table 1 reveals that the likely exposure to canthaxanthin from salmon flesh is highly unlikely to reach the Acceptable Daily Intake (ADI) set for canthaxanthin. Another way to assess risk is to back-calculate what would have to be consumed by humans in order to reach established ‘safe-limit’ levels. The Food Advisory Committee of the UK Food Standards Agency, the Scientific Committee on Animal Nutrition (SCAN) and the Scientific Committee on Food (SCF) have all agreed that an ADI of canthaxanthin is around 0.03 mg/kg body weight/day.
241
For an adult weighing 75 kg, this equates to a safe intake level for canthaxanthin of 2.25 mg/day (15.75 mg canthaxanthin/week, or > 1.5 kg salmon per week). In Norway, the nation with the highest per capita fish consumption amongst the salmon producing nations, the total fish consumption (all fish and shellfish) amounts to under 1 kg per person per week (World Resources Institute internet page). In fact, the three generous portions of well pigmented salmon would only exceed the ADI in 20 kg children (around 5 years of age), but the value for salmon consumption used above is far higher than what a survey would reveal about the eating habits of the young. A 1989 survey by the UK Department of Health showed that only 5% of children between the ages of 4 and 18 actually consumed salmon, and that 97.5% of those consumed less than two portions per week. When considered that canthaxanthin is slowly cleared from the body on termination of consumption of salmon, it is clear that consumption of canthaxanthin through salmon intake poses no threat to the population. Do remember, the figures used above have always deliberately taken ‘worst-case’ (high concentration, high intake) scenarios. Remember also that ADIs set also build in a margin of error so that, in reality, it is very likely that canthaxanthin is not dangerous even slightly above levels advised. Of course, consumption of canthaxanthin at levels above the ADI for extended periods of time cannot be supported.
Overdosing with canthaxanthin Since it was found that canthaxanthin was able to deposit non-specifically in sub-epidermal fat layers, thereby producing an orange hue reminiscent of a suntan, the carotenoid has been incorporated into oral capsules. The goal of the sun-tanning pills was to rapidly build up the body’s canthaxanthin deposits (in what is termed a ‘saturation phase’) and then to sustain the fat deposits at a level providing sufficient skin colour so as to mimic a natural sun-tan. Adult individuals taking these pills were often taking around 70 mg per day, every day for several years (from Arden & Barker, 1991). As with any nutrient or additive, it is possible to overdose on canthaxanthin. In some individuals, prolonged excessive intake of canthaxanthin through use of ‘sunless tanning’ products may result in macular (eye) crystal deposition. In most cases there is no visual disturbance, and crystals will resorb following cessation of canthaxanthin intake (Arden & Barker). Regarding macular crystal formation, Norris et al. (1989) estimated a no-effect level (NOEL) of canthaxanthin at an intake of around 15–60 mg/day. Koepcke et al. (1994: unpublished report for WHO) refined this figure to a NOEL of 30 mg per day. Remember that the ADI set for a 75 kg person is 2.25 mg per day.
242
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
Table 1. Possible human dietary exposure to canthaxanthin originating from salmon, in comparison to ADI and NOEL published for canthaxanthin
Salmon feed dose Attained salmon fillet level Possible weekly Cx intake (from 3150 g portions) Daily intake per kg body weight in 75 kg adult ADI (amount of Cx per kg body weight per day) NOEL (amount of Cx per kg body weight per day)
Since the link between oral canthaxanthin overdose and macular crystal formation became apparent (Cortin, Corriveau, Rousseau, Tardif, Malenfant, & Boudreault, 1982) there has been pressure to remove canthaxanthin from the list of permitted feed additives. Other side-effects of canthaxanthin over-dosage have been claimed. It is rather likely that a coincidence between an individual taking canthaxanthin supplements, and an onset of a health problem were correlated purely because it was noticed that symptoms may not have been too dissimilar to those observed during acute hypervitaminosis A. However, in humans, canthaxanthin has no pro-vitamin A role. The effect of canthaxanthin on liver histology has been studied in rats (Buser, 1992: unpublished report for WHO). Buser reported that at high canthaxanthin intakes (> 75 mg/kg BW/day) canthaxanthin induced subtle changes in liver lipid cells and discoloration linked to carotenoid deposition in fatty structures. No adverse effects were recorded despite the changes, and all changes were reversible upon cessation of canthaxanthin intake. A NOEL regarding liver alteration was set at 5 mg/kg BW/day, this level already being far in excess of the ADI suggested in humans. Similar findings have also been reported for monkeys (Buser et al., 1993: unpublished report for WHO). Canthaxanthin intake has never been firmly correlated to any disease, quite unlike common table salt. Countries where canthaxanthin has been the sole pigment source for salmonids do not report incidences of canthaxanthin related pathologies.
Low estimate
High estimate
40–80 mg/kg 6 mg/kg
10 mg/kg
2.7 mg 0.005 mg 0.03 mg 0.25 mg
4.5 mg 0.008 mg
Epidemiological studies suggest that consumption of foods containing beta-carotene, lycopene and other carotenoids may be effective against certain types of cancer (Peto, Doll, Buckley, & Sporn, 1981). Medical studies have since confirmed that this is also the case for canthaxanthin. In mice, Rybski, Grogan, Aickin, and Genlser (1991) and Gensler (1989) showed that canthaxanthin was able to reduce UV light-induced tumours. The rat liver cell study of Gradelet and co-workers (1998) demonstrated canthaxanthin’s anti-cancer activity against carcinogenic compounds. However, Buser (1992: unpublished report for WHO) conducted a 2year long-term rat study and revealed no treatment effects of canthaxanthin on survival of rats. He saw no effect of canthaxanthin on tumour occurrence even at his highest dose (250 mg/kg BW/day). The Scientific Committee for Food (SCF) (1997) opinion on canthaxanthin further states clearly that in rats ‘‘no changes in tumour incidence were noted even at [a dietary dose of] 1000mg/kg BW’’. Ingested canthaxanthin was successful in significantly reducing the incidence of oral cancers in hamsters (Schwartz & Shklar, 1988). More recent work from Palozza et al. (1998), revealed that canthaxanthin inhibited cancer cell growth in human cancer cell lines. What is absolutely clear is that canthaxanthin is not responsible for any increases in tumour incidence, and is in fact likely to function in an anti-carcinogenic manner under certain conditions.
A reasonable intake of canthaxanthin Canthaxanthin: an in vitro antioxidant and tumour suppressant Many carotenoids have been ascribed antioxidant roles (Krinsky, 1993). In vitro, it has been observed that canthaxanthin also has antioxidant capabilities (Packer, 1993). Furthermore, this effect has been recorded in membrane model systems (Palozza & Krinsky, 1992), in liposomes (Woodall, Britton, & Jackson, 1997), and in isolated liver-cells from rats previously fed canthaxanthin and then subjected to aflatoxin induced damage (Gradelet, Le Bon, Berge´s, Suschetet, & Astorg, 1998).
There are positive health roles of canthaxanthin, including some not thoroughly covered so far in this review. For example, dermal-protection against the sun’s UV-radiation is demonstrated in mice (MathewsRoth, 1982). However, there are problems (real or perceived) associated with overdoses of this carotenoid, as there are with vitamins, minerals, common table salt, etc. Based on scientific literature, various food safety regulatory bodies have chosen an ADI of max 0.03 mg canthaxanthin per kg bodyweight per day. This level is considered to be well within safe limits, and averaged
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
out over the week is not likely to be exceeded by a bulk of the population. A NOEL for humans has been suggested to be 0.25 mg/kg BW/day. In humans, it is conceivable, that a person frequently consuming relatively large quantities of canthaxanthinpigmented salmon could exceed the ADI. Given the fact that (1) ADI values are conservative, (2) body stores of fat-soluble compounds are depleted during periods of lower intake, (3) it is unlikely that an individual would frequently consume great quantities of canthaxanthin containing foods, and (4) the only proven side-effect of moderate over-dosage is the reversible, non-damaging, deposition of crystals in the eye, the risk of harmful effects of canthaxanthin supplementation into aquafeeds is negligible. Safe-guarding canthaxanthin use in aquaculture allows the flexibility in production needed to sustain modern, safe fish-farming practices, and a year-round supply of quality salmon products for the healthconscious consumer.
References Arden, G. B., & Barker, F. M. (1991). Canthaxanthin and the eye: a critical ocular toxicologic assessment. Journal of Toxicology — Cuticular and Ocular Toxicology, 10, 115–155. Baker, R. T. M., Pfeiffer, A.-M., Schoener, F.-J., & Smith-Lemmon, L. (in press). Pigmenting efficacy of astaxanthin and canthaxanthin in fresh-water reared Atlantic salmon, Salmo salar. Animal Feed Science and Technology. Buttle, L. G., Crampton, V. O., & Williams, P. D. (2001). The effect of feed pigment type on flesh pigment deposition and colour in farmed Atlantic salmon, Salmo salar L. Aquaculture Research, 32, 103–111. Cortin, P., Corriveau, L. A., Rousseau, A. P., Tardif, Y., Malenfant, M., & Boudreault, G. (1982). Maculopathie en paillettes d’or. Canadian Journal of Opthalmology, 17, 103. Gensler, H. L. (1989). Reduction of immunosuppression in UVirradiated mice by dietary retinyl palmitate plus canthaxanthin. Carcinogenesis, 10, 203–207. Gradelet, S., Le Bon, A.-M., Berge`s, R., Suschetet, M., & Astorg, P. (1998). Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DANN damage in the rat: role of the
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modulation of aflatoxin B1 metabolism. Carcinogenesis, 19, 403–411. Krinsky, N. I. (1993). Actions of carotenoids in biological systems. Annual Reviews in Nutrition, 13, 561–587. Mathews-Roth, M. M. (1982). Antitumor activity of beta-carotene, canthaxanthin and phytoene. Oncology, 39, 33–37. Møller, A. P., Biard, C., Blount, J. D., Houston, D. C., Ninni, P., Saino, N., & Surai, P. F. (2000). Carotenoid-dependent signals: indicators of foraging efficiency, immunocompetence or detoxification ability? Avian and Poultry Biology Reviews, 11, 137–159. Norris, P. G., Arden, G. B., Oluwole, J. O. A., Polinghorne, P., Bird, A. C., & Hawk, J. L. M. (1989). Ophthalmological and electrophysiological monitoring of patients taking canthaxanthin and beta-carotene. American Society of Photobiology, abstract 21S. Packer, L. (1993). Antioxidant action of carotenoids in vitro and in vivo and protection against oxidation of human low-density lipoproteins. In L. M. Canfield, N. I. Krinsky, & J. A. Olson (Eds.), Carotenoids in human health. Annals of the New York Academy of Sciences, 691, 48–60. Palozza, P., & Krinsky, N. I. (1992). Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. Archives of Biochemistry and Biophysics, 297, 291–295. Peto, R., Doll, R., Buckley, J. D., & Sporn, M. B. (1981). Can dietary beta-carotene materially reduce human cancer rates? Nature, 290, 201–208. Rybski, J. A., Grogan, T. M., Aickin, M., & Gensler, H. (1991). Reduction of murine cutaneous UVB-induced tumour-infiltrating T lymphocytes by dietary canthaxanthin. Journal of Investigational Dermatology, 97, 892–897. Scientific Committee for Food. (1997). Opinion on canthaxanthin. CS/ADD/COL/133-Final. Storebakken, T., & Choubert, G. (1991). Flesh pigmentation of rainbow trout fed astaxanthin or canthaxanthin at different feeding rates in freshwater and saltwater. Aquaculture, 95, 289–295. Torrissen, O. J. (1986). Pigmentation of salmonids—a comparison of astaxanthin and canthaxanthin as pigment sources for rainbow trout. Aquaculture, 53, 271–278. Torres, I. C., Mira, L., Ornelas, C. P., & Melim, A. (2000). Study of the effects of dietary fish intake on serum lipids and lipoproteins in two populations with different dietary habits. British Journal of Nutrition, 83, 371–379. Woodall, A. A., Britton, G., & Jackson, M. J. (1997). Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: relationship between carotenoid structure and protective ability. Biochimica et Biophysica Acta, 1336, 575–586.
Viewpoint
Canthaxanthin in aquafeed applications: is there any risk? Re´mi T.M. Baker BASF AG, 67056 Ludwigshafen, Germany (e-mail: [email protected])
The carotenoid pigment ‘canthaxanthin’ has been used in aquafeed for many years in order to impart the desired flesh colour in farmed salmonids. A side effect of extreme overdosage of this carotenoid is the deposition of minute crystals in the eye, a fact leading to adverse media attention for canthaxanthin in the past, and some pressure to limit its use aquafeeds. A real appraisal of the possible amount of canthaxanthin ingested by humans through the consumption of notable quantities of highly pigmented salmon, reveals that it is extremely unlikely that consumers could be exposed to sufficient canthaxanthin to attain the established ADI for this pigment. Additionally, the ADI is 10 times lower than the reported no-effect level (NOEL) for canthaxanthin. Therefore, canthaxanthin is a safe source of carotenoids for salmonid feeds. # 2001 Elsevier Science Ltd. All rights reserved.
In marine ecosystems, canthaxanthin is found in algae, bacteria and in crustacea, but subsequently accumulated in fish upon consumption of prey items. With aquaculture, it has been possible to enrich the flesh of species such as salmon with canthaxanthin, by utilizing commercial preparations of this pigment in the manufacture of pelleted feeds. This is possible because fish have the capability to transport and deposit this pigment at specific sites in their muscle, just like the canthaxanthin molecules encountered in the wild. The motivation for increasing flesh levels of carotenoids is that without them, flesh from trout and salmon would be less visually attractive, and therefore would be less valued as a seafood. After all, who can deny the appeal of richly coloured smoked salmon for example? Without dietary supplementation of these pigments, the aquaculture industry would find it hard to support the production of salmonid species because fish demand is driven through consumer demand for quality products. Bear in mind that the consumption of salmonid flesh is a great contributor to the intake of n-3 fatty acids in humans, and thus has the potential to supply important nutritional factors for human health (Torres, Mira, Ornelas, & Melim, 2000). Much research indicates that intake of fish should be increased in order to improve resistance to coronary heart disease for example. In many of the mature retail markets, affordable, attractive salmon is key to these health drives. Astaxanthin is very well accepted as a feed pigment, but historically, canthaxanthin abuse in sunless tanning applications has led to some resistance against the widespread use of canthaxanthin. Is there a real risk to canthaxanthin’s use in fish feeds?
Flesh deposition of canthaxanthin Introduction For many years now, astaxanthin has been the main flesh-colouring pigment of choice in a bulk of the trout and salmon farming industries. Synthesized formulations of canthaxanthin have also been very successfully applied with similar results to those obtained with astaxanthin. Both astaxanthin and canthaxanthin are found in nature, where they play important roles in animal displays of maturity and in the protection of tissues (plant and animal) against oxidising free radicals (Møller et al., 2000).
Many studies have demonstrated that astaxanthin is more efficiently deposited than canthaxanthin in rainbow trout (Storebakken & Choubert, 1991; Torrissen, 1986). The same is not true of Atlantic salmon as has been highlighted by Baker et al. (in press), the work of Buttle, Crampton, and Williams (2001) and in numerous unpublished commercial-scale trials. The difference may be due to genetic background and/or environment, although it has been previously shown that salinity is not a factor accounting for the difference (Baker et al.). Wide-scale application of canthaxanthin in rainbow trout feeds is unlikely. In Atlantic salmon pigmentation,
0924-2244/02/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S 0 92 4 - 2 24 4 ( 0 1 ) 0 0 09 1 - 7
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
however, canthaxanthin has been widely used in Britain, Canada and more recently Chile (pers. obs.), in some cases, 100% of the feed pigment coming from this one source. Feed levels of pigment vary from one fish producer to the next, depending on feed regulations, intended market, and producer-designed feeding regimes. These feeding regimes are designed to get the salmon to an intended colour target as cost efficiently as possible without incurring risks of under-pigmentation. Whilst some producers favour an early high start-dose, decreasing as the fish gets closer to harvest, others opt for a late starting regime. A moderate flat-dose is also commonly used. Feed supplementation levels for canthaxanthin tend to range between 40 and 80 mg/kg, similar to the doses normally applied for astaxanthin. Whatever the regime employed, the canthaxanthin content of flesh from 4 kg harvested salmon fed aquafeed dosed with commercial canthaxanthin preparations usually lies within the range 6–10 mg canthaxanthin per kg flesh.
Human intake of canthaxanthin from salmon Taking the figures shown above, and assuming that a typical portion of fresh salmon for consumers is 100– 200 g, this equates to a range of human canthaxanthin intake of between 0.6 and 2.0 mg for that portion. A weekly normal figure for the consumption of salmon is hard to define given the differences between countries. Because of associated n-3 fatty acid intake, many nutritionists advise that 2–3 portions of oily fish (such as salmon) would be beneficial in a balanced diet. The Food Standards Agency (2001) have more recently advised that at least one portion of oily fish should be consumed per week. Assuming that three portions of salmon are in fact consumed, that highly pigmented salmon is taken, and that a portion is 150 g, the weekly intake of canthaxanthin would be 4.5 mg (0.64 mg/day). This is on the extreme side already, as this would represent an annual salmon intake of 23.4 kg. As a comparison, the total per capita seafood consumption in France (fish and substantial amounts of shellfish) in 1997 was estimated at 27.5 kg (World Resources Institute internet page). Nevertheless, using these generous estimates, Table 1 reveals that the likely exposure to canthaxanthin from salmon flesh is highly unlikely to reach the Acceptable Daily Intake (ADI) set for canthaxanthin. Another way to assess risk is to back-calculate what would have to be consumed by humans in order to reach established ‘safe-limit’ levels. The Food Advisory Committee of the UK Food Standards Agency, the Scientific Committee on Animal Nutrition (SCAN) and the Scientific Committee on Food (SCF) have all agreed that an ADI of canthaxanthin is around 0.03 mg/kg body weight/day.
241
For an adult weighing 75 kg, this equates to a safe intake level for canthaxanthin of 2.25 mg/day (15.75 mg canthaxanthin/week, or > 1.5 kg salmon per week). In Norway, the nation with the highest per capita fish consumption amongst the salmon producing nations, the total fish consumption (all fish and shellfish) amounts to under 1 kg per person per week (World Resources Institute internet page). In fact, the three generous portions of well pigmented salmon would only exceed the ADI in 20 kg children (around 5 years of age), but the value for salmon consumption used above is far higher than what a survey would reveal about the eating habits of the young. A 1989 survey by the UK Department of Health showed that only 5% of children between the ages of 4 and 18 actually consumed salmon, and that 97.5% of those consumed less than two portions per week. When considered that canthaxanthin is slowly cleared from the body on termination of consumption of salmon, it is clear that consumption of canthaxanthin through salmon intake poses no threat to the population. Do remember, the figures used above have always deliberately taken ‘worst-case’ (high concentration, high intake) scenarios. Remember also that ADIs set also build in a margin of error so that, in reality, it is very likely that canthaxanthin is not dangerous even slightly above levels advised. Of course, consumption of canthaxanthin at levels above the ADI for extended periods of time cannot be supported.
Overdosing with canthaxanthin Since it was found that canthaxanthin was able to deposit non-specifically in sub-epidermal fat layers, thereby producing an orange hue reminiscent of a suntan, the carotenoid has been incorporated into oral capsules. The goal of the sun-tanning pills was to rapidly build up the body’s canthaxanthin deposits (in what is termed a ‘saturation phase’) and then to sustain the fat deposits at a level providing sufficient skin colour so as to mimic a natural sun-tan. Adult individuals taking these pills were often taking around 70 mg per day, every day for several years (from Arden & Barker, 1991). As with any nutrient or additive, it is possible to overdose on canthaxanthin. In some individuals, prolonged excessive intake of canthaxanthin through use of ‘sunless tanning’ products may result in macular (eye) crystal deposition. In most cases there is no visual disturbance, and crystals will resorb following cessation of canthaxanthin intake (Arden & Barker). Regarding macular crystal formation, Norris et al. (1989) estimated a no-effect level (NOEL) of canthaxanthin at an intake of around 15–60 mg/day. Koepcke et al. (1994: unpublished report for WHO) refined this figure to a NOEL of 30 mg per day. Remember that the ADI set for a 75 kg person is 2.25 mg per day.
242
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
Table 1. Possible human dietary exposure to canthaxanthin originating from salmon, in comparison to ADI and NOEL published for canthaxanthin
Salmon feed dose Attained salmon fillet level Possible weekly Cx intake (from 3150 g portions) Daily intake per kg body weight in 75 kg adult ADI (amount of Cx per kg body weight per day) NOEL (amount of Cx per kg body weight per day)
Since the link between oral canthaxanthin overdose and macular crystal formation became apparent (Cortin, Corriveau, Rousseau, Tardif, Malenfant, & Boudreault, 1982) there has been pressure to remove canthaxanthin from the list of permitted feed additives. Other side-effects of canthaxanthin over-dosage have been claimed. It is rather likely that a coincidence between an individual taking canthaxanthin supplements, and an onset of a health problem were correlated purely because it was noticed that symptoms may not have been too dissimilar to those observed during acute hypervitaminosis A. However, in humans, canthaxanthin has no pro-vitamin A role. The effect of canthaxanthin on liver histology has been studied in rats (Buser, 1992: unpublished report for WHO). Buser reported that at high canthaxanthin intakes (> 75 mg/kg BW/day) canthaxanthin induced subtle changes in liver lipid cells and discoloration linked to carotenoid deposition in fatty structures. No adverse effects were recorded despite the changes, and all changes were reversible upon cessation of canthaxanthin intake. A NOEL regarding liver alteration was set at 5 mg/kg BW/day, this level already being far in excess of the ADI suggested in humans. Similar findings have also been reported for monkeys (Buser et al., 1993: unpublished report for WHO). Canthaxanthin intake has never been firmly correlated to any disease, quite unlike common table salt. Countries where canthaxanthin has been the sole pigment source for salmonids do not report incidences of canthaxanthin related pathologies.
Low estimate
High estimate
40–80 mg/kg 6 mg/kg
10 mg/kg
2.7 mg 0.005 mg 0.03 mg 0.25 mg
4.5 mg 0.008 mg
Epidemiological studies suggest that consumption of foods containing beta-carotene, lycopene and other carotenoids may be effective against certain types of cancer (Peto, Doll, Buckley, & Sporn, 1981). Medical studies have since confirmed that this is also the case for canthaxanthin. In mice, Rybski, Grogan, Aickin, and Genlser (1991) and Gensler (1989) showed that canthaxanthin was able to reduce UV light-induced tumours. The rat liver cell study of Gradelet and co-workers (1998) demonstrated canthaxanthin’s anti-cancer activity against carcinogenic compounds. However, Buser (1992: unpublished report for WHO) conducted a 2year long-term rat study and revealed no treatment effects of canthaxanthin on survival of rats. He saw no effect of canthaxanthin on tumour occurrence even at his highest dose (250 mg/kg BW/day). The Scientific Committee for Food (SCF) (1997) opinion on canthaxanthin further states clearly that in rats ‘‘no changes in tumour incidence were noted even at [a dietary dose of] 1000mg/kg BW’’. Ingested canthaxanthin was successful in significantly reducing the incidence of oral cancers in hamsters (Schwartz & Shklar, 1988). More recent work from Palozza et al. (1998), revealed that canthaxanthin inhibited cancer cell growth in human cancer cell lines. What is absolutely clear is that canthaxanthin is not responsible for any increases in tumour incidence, and is in fact likely to function in an anti-carcinogenic manner under certain conditions.
A reasonable intake of canthaxanthin Canthaxanthin: an in vitro antioxidant and tumour suppressant Many carotenoids have been ascribed antioxidant roles (Krinsky, 1993). In vitro, it has been observed that canthaxanthin also has antioxidant capabilities (Packer, 1993). Furthermore, this effect has been recorded in membrane model systems (Palozza & Krinsky, 1992), in liposomes (Woodall, Britton, & Jackson, 1997), and in isolated liver-cells from rats previously fed canthaxanthin and then subjected to aflatoxin induced damage (Gradelet, Le Bon, Berge´s, Suschetet, & Astorg, 1998).
There are positive health roles of canthaxanthin, including some not thoroughly covered so far in this review. For example, dermal-protection against the sun’s UV-radiation is demonstrated in mice (MathewsRoth, 1982). However, there are problems (real or perceived) associated with overdoses of this carotenoid, as there are with vitamins, minerals, common table salt, etc. Based on scientific literature, various food safety regulatory bodies have chosen an ADI of max 0.03 mg canthaxanthin per kg bodyweight per day. This level is considered to be well within safe limits, and averaged
R.T.M. Baker / Trends in Food Science & Technology 12 (2002) 240–243
out over the week is not likely to be exceeded by a bulk of the population. A NOEL for humans has been suggested to be 0.25 mg/kg BW/day. In humans, it is conceivable, that a person frequently consuming relatively large quantities of canthaxanthinpigmented salmon could exceed the ADI. Given the fact that (1) ADI values are conservative, (2) body stores of fat-soluble compounds are depleted during periods of lower intake, (3) it is unlikely that an individual would frequently consume great quantities of canthaxanthin containing foods, and (4) the only proven side-effect of moderate over-dosage is the reversible, non-damaging, deposition of crystals in the eye, the risk of harmful effects of canthaxanthin supplementation into aquafeeds is negligible. Safe-guarding canthaxanthin use in aquaculture allows the flexibility in production needed to sustain modern, safe fish-farming practices, and a year-round supply of quality salmon products for the healthconscious consumer.
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