1

Fish as a dietary source of healthy

long chain n-3 polyunsaturated fatty

acids (LC n-3 PUFA) and vitamin D

A Review of Current Literature

June 2012

Baukje de Roos

Alan Sneddon

Helen Macdonald

2

FACTS…

… AND OUTSTANDING ISSUES

Consumption of fish protects against stroke and lowers the risk of mortality from

coronary heart disease

The exact mechanisms through which fatty acids (and perhaps vitamin D) in fish

influence cardiovascular disease development are not completely understood

The UK recommendation is that people eat at least two portions (with a portion

being 140 g) of fish per week, one of which should be oily fish

Despite recommendations, and sufficient availability, the majority of the UK

population does not consume enough fish, particularly oily fish, and should be

encouraged to increase consumption

The measurement of the Omega-3 Index in blood can be used to establish

desirable intakes of fish

We do not have information on the average Omega-3 Index in the UK

population, or how the index can be increased by consuming certain fish

There is no convincing evidence that consumption of methylmercury in fish

increases the risk of coronary heart disease. Any potential cancer risks associated

with dioxins in fish are well below the well established coronary heart disease

benefits from fish consumption

Among infants, young children and adolescents, the available data are currently

insufficient to establish the health risks and health benefits of eating fish

To claim that a product is a source of vitamin D it should contain 15% of the

recommended daily amount (RDA) in 100g or, to make a high vitamin D claim,

the product should contain 30% of the RDA. It is very likely that a high vitamin D

claim could be made for many oily fish products.

In recent years, there has been more information in the press and on websites

regarding the growing prevalence of vitamin D deficiency but it is unlikely that

this deficiency is widely recognised by consumers.

There is limited evidence that farmed salmon may contain significantly lower

levels of vitamin D compared with wild salmon, at least in the USA

We need more information on vitamin D levels in farmed versus wild oily fish,

and understand how vitamin D levels vary between seasons and geographical

regions within the UK

In Atlantic salmon, vitamin D levels in muscle have been shown to be improved

by increasing dietary levels of the vitamin

There is potential to further improve the healthiness of farmed fish by

increasing endogenous vitamin D levels through different feeding regimes

3

FISH CONSUMPTION IN THE UK

In the last five decades, total and per capita fish food supplies have expanded significantly. The total supply of

fish for food consumption has increased at an annual rate of 3.1 percent since 1961, while the world

population has increased by 1.7 percent per year in the same period. Annual per capita fish consumption

grew from an average of 9.9 kilograms in the 1960s to 11.5 kilograms in the 1970s, 12.6 kilograms in the

1980s, 14.4 kilograms in the 1990s and reached 17.0 kilograms in 2007 (Figure 1). The general growth in fish

consumption has had different impacts among countries and regions (1).

Figure 1. Per capita supply of fish between 2005 and 2007. Reproduced from (1).

In the last two decades, mainly before the food and economic crises, the global food market, including the

fish market, experienced unprecedented expansion and a change in global dietary patterns, with a shift

towards consumption of more dietary protein. This change was the result of complex interactions of several

factors, including rising living standards, population growth, rapid urbanization, increased trade and

transformations in food distribution. In addition, world food markets have become more flexible, with new

products entering the markets, including value-added products easier to prepare for the consumer. Growing

urbanization is one of the factors modifying patterns of food consumption, which has also had an impact on

demand for fishery products (1).

However, throughout Europe, substantial variation exists in total fish intake, fish sub-groups and the number

of types consumed between regions. Day-to-day variability in consumption is also high. A six- to sevenfold

4

variation in total fish consumption exists in women and men – the lowest consumption was found in Germany

whereas the highest consumption was in Spain. In general, consumption of white fish represented 49% and

45% of the intake of total fish in women and men, respectively, with the greatest consumption in Spain and

Greece and the least consumption in the Germany and the Netherlands. The coastal areas of northern Europe

(Denmark, Sweden and Norway) and Germany showed the highest intake of very fatty fish (Figure 2) (2).

Figure 2. Contribution of different fish subgroups to total consumption of fish (in grams per day) in a) women and b)

men. Abbreviations: GRE: Greece; SPA: Spain; ITA: Italy; FRA: France; GER: Germany; NLD: The Netherlands; UK: United

Kingdom; DEK: Denmark; SWE: Sweden; NOR: Norway. Reproduced from (2).

It was recently stressed that current world supplies of wild and farmed fish and fish-derived fish oil might be

insufficient to meet recommended LC n-3 PUFA intakes globally, especially for EPA and DHA. In addition, the

world demand for seafood is predicted to grow over the next several decades, putting further strains on world

seafood supplies (3).

5

BENEFICIAL HEALTH EFFECTS OF FISH: LC N-3 PUFA

Systematic reviews, assessing all available evidence from fish oil intervention studies, have shown a protective

effect of fish intake on stroke and on fatal coronary heart disease. The reviews concluded that consumption of

fish decreases rates of all-cause mortality, cardiac and sudden death, and possibly stroke. Furthermore, the

benefits of fish oil were stronger in secondary compared with primary prevention settings, and adverse

effects appeared to be minor (4-6). The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA)

eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), also known as omega-3 fatty acids, are believed

to be mainly responsible for these beneficial effects of fish consumption.

The exact mechanisms through which LC n-3 PUFA influence cardiovascular disease development are not

established in detail, but probably include a decrease in plasma levels of fasting and postprandial

triacylglycerol, decreased atherosclerosis, a decrease in arrhythmias, modulation of platelet aggregation and

decreased synthesis of pro-inflammatory agents:

Triacylglycerol-lowering properties are amongst the best established in vivo actions of LC n-3 PUFA. A

review of placebo-controlled human studies concluded that an average intake of 3 to 4 grams per day of

LC n-3 PUFA decreases serum triacylglycerol concentrations by 25-30% in a dose dependent manner (7).

Based on the triacylglycerol-lowering effects of LC n-3 PUFA, the American Food and Drug Administration

have approved a prescription form of LC n-3 PUFA fatty acids. Lovaza™ (formerly known as Omacor) is

prescribed as an adjunct to appropriate diet for the treatment of very high triacylglycerol levels (> 5.65

millimoles per liter) in adults. Each one gram capsule of Lovaza™ contains approximately 465 milligrams of

EPA ethyl esters and 375 milligrams of DHA ethyl esters. Clinical trials have shown that administration of 4

grams per day of Lovaza™ results in a decrease in triacylglycerol levels of 30 to 50% (8-11).

The proposed beneficial effects of physiological doses of LC n-3 PUFA on atherosclerosis in humans or

animal models are not convincing (12). Fish oil concentrate had only modest anti-atherosclerotic potential

in patients with angiographically proven coronary artery disease (13), but twelve randomised trials on the

effect of fish oil on restenosis of carotid arteries after percutaneous transluminal coronary angioplasty

(PTCA) or coronary artery bypass graft (CABG) showed equivocal effects (14). Additionally, a randomised

intervention study on the effects of fish oil versus placebo on intima media thickness and the media of the

carotid artery indicated worsening rather than improvement upon fish oil supplementation (15).

6

Evidence from both in vivo and in vitro animal studies suggests that LC n-3 PUFA may decrease

arrhythmias (16;17). Three trials in patients with implantable cardioverter defibrillators, however, did not

show a strong protective effect of fish oil on life-threatening ventricular arrhythmia (18-20).

LC n-3 PUFA may decrease the risk of atherothrombosis by affecting platelet aggregation and

haemostasis, at least in vitro. The effects of LC n-3 PUFA on haemostatic function and thrombogenesis in

vivo are, however, unclear. Results of measurements of platelet aggregation after dietary LC n-3 PUFA

intervention have yielded inconsistent findings, partly because of differences in study design, the source

and quantity of these fatty acids given, and methodology (21;22).

Evidence from in vitro studies indicates that LC n-3 PUFA significantly affect mechanisms relating to

inflammatory processes. Inflammatory processes play an important role in the development and

progression of atherosclerosis, and thus myocardial infarction. However, it has so far been very difficult to

provide evidence for the anti-inflammatory effects LC n-3 PUFA in humans in vivo. LC n-3 PUFA do not

appear to affect the most extensively studied clinical marker of inflammation, C-reactive protein (CRP).

There is, however, considerable debate regarding the usefulness of CRP as a risk biomarker of CHD and its

potential causal role in atherogenesis (12).

Figure 3. Schema of potential dose responses and time courses for altering clinical events of physiologic effects of fish or fish oil

intake. The relative strength of effect is estimated from effects of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) on each

risk factor and on the corresponding impact on cardiovascular risk. For example, dose response for antiarrhythmic effects is initially

steep with a subsequent plateau, and clinical benefits may occur within weeks, while dose response for triglyceride effects is more

gradual and monotonic, and clinical benefits may require years of intake. Reproduced from (6).

7

Studies assessing the mechanisms by which fish beneficially affect health outcomes have shown that a higher

dose of at least 1.0 to 1.5 grams per day of LC n-3 PUFA is required for demonstrable beneficial effects on

cardiovascular risk factors such as a reduction of plasma triacylglycerol levels, blood pressure, platelet

aggregation and the inflammatory response (Figure 3) (6). However, as such doses are significantly higher

than the doses required for a decrease in mortality from coronary heart disease (23), it is questionable

whether the above mentioned beneficial effects of LC n-3 PUFA could explain the beneficial effect on

coronary heart disease mortality (12).

A relatively new efficacy biomarker of fish intake is the Omega-3 Index. This Index is defined as the total levels

of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) as a percentage of the total fatty acid levels

in erythrocytes. This index is not only a biomarker of intake, but now also emerging as a risk factor for fatal

and non-fatal cardiovascular events. A standardised analysis of fatty acid patterns correctly classifies persons

to either low, intermediate or high risk. Circumstantial evidence indicates that determining the Omega-3

Index has a therapeutic consequence. Thus, the Omega-3 Index fulfils important criteria for a novel

biomarker, set forth by the American Heart Association and others, and compares well to other novel

biomarkers (24;25). An optimal target level of the Omega-3 Index is 8%, and an undesirable level is less than

4%, with 4–8% being an intermediate-risk zone.

FISH AS A DIETARY SOURCE OF LC N-3 PUFA

Consumption of fish provides energy, protein and a range of other important nutrients, including the long-

chain n-3 polyunsaturated fatty acids (LC n3 PUFA) and micronutrients (including various vitamins and

minerals) (26). A portion of 140 g of fish provides about 50–60% of the daily protein requirements for an

adult. Fish is usually low in saturated fats, carbohydrates and cholesterol (1).

In 1994, the UK Committee on Medical Aspects of Food Policy (COMA) recommended that people eat at least

two portions (with a portion being 140 g) of fish per week, one of which should be oily fish (27). The COMA

population recommendation was endorsed by the Scientific Advisory Committee on Nutrition (SACN) in 2004

(28). In their report, SACN emphasized that this recommendation represents a minimal and achievable

average population goal and does not correspond to the level of fish consumption required for maximum

nutritional benefit. They further recommended that women past reproductive age, boys and men should aim

to consume within the range of one to four portions of oily fish a week, based on maintaining consumption of

dioxins and dioxin-like PCBs below the guideline value of 8 picograms WHO-TEQ per kilogram bodyweight per

day (28). Two portions of fish per week, one white and one oily, provide approximately 0.45 grams per day of

LC n-3 PUFA.

8

On an international level, health organizations and government agencies are typically recommending intakes

of LC n-3 PUFA that either maintain the status quo (about 100-200 milligrams per day in most Western

countries) or are intended for the prevention of cardiovascular disease (about 400-600 milligrams per day),

the treatment of patients with cardiovascular disease (about 1 gram per day), or the treatment of

hypertriglyceridaemia (about 2-4 grams per day) (29).

Despite the COMA and SACN recommendation to eat at least two portions of fish per week, and the per

capita expansion of fish food supplies, the majority of the UK population does not consume enough fish,

particularly oily fish, and should be encouraged to increase consumption (26).

In 2010, the Food and Agriculture Organization of the United Nations and the World Health Organization

convened a joint Expert Consultation on the risks and benefits of fish consumption. They recommended a

series of steps to better asses and manage the risks and benefits of fish consumption and more effectively

communicate these risks and benefits to citizens. Their main conclusion was that among the general adult

population, consumption of fish, particularly fatty fish, lowers the risk of mortality from coronary heart

disease, whilst there is an absence of probable or convincing evidence of risk of coronary heart disease

associated with methylmercury from fish. Potential cancer risks associated with dioxins in fish are well below

established coronary heart disease benefits from fish consumption (26).

In pregnancy and lactation there is a demand on the mother to supply the foetus and infant with LC n-3 PUFA,

which are required for the development of the central nervous system. There is some evidence that increased

maternal LC n-3 PUFA intake produces beneficial effects, especially in lower birth weight populations, and this

may be more relevant in populations that tend to have a lower background intake of LC n-3 PUFA, i.e. where

fish intake is low. No adverse effects of maternal LC n-3 PUFA supplementation have been observed, even at

relatively high doses (28). When comparing the benefits of LC n-3 PUFA with the risks of methylmercury

among women of childbearing age, maternal fish consumption lowers the risk of suboptimal

neurodevelopment in their offspring compared with the offspring of women not eating fish in most

circumstances evaluated (26). At levels of maternal exposure to dioxins (from fish and other dietary sources)

that do not exceed the provisional tolerable monthly intake (PTMI) of 70 picograms per kilogram body weight

established by JECFA (for PCDDs, PCDFs and coplanar PCBs), neurodevelopmental risk for the foetus is

negligible.

Among infants, young children and adolescents, the available data are currently insufficient to derive a

quantitative framework of the health risks and health benefits of eating fish. However, healthy dietary

patterns that include fish consumption and are established early in life influence dietary habits and health

during adult life (26).

9

Maximal health benefit from fish consumption could be achieved by consumption of:

- One serving (100 grams) per week of fish with and EPA+DHA concentration of greater than 1.5 grams per

100 grams (such as fresh salmon, pickled/smoked/canned sardines and pilchards, kipper);

- Two servings (each 100 grams) per week of fish with and EPA+DHA concentration between 0.8 – 1.5 grams

per 100 grams (such as canned/smoked salmon, canned sardines, fresh trout, herring, fresh tuna, fresh

mackerel);

- Four servings (each 100 grams) per week of fish with and EPA+DHA concentration between 0.3 – 0.8 grams

per 100 grams (such as canned tuna, fresh place and whiting)

- Seven servings (each 100 grams) per week of fish with an EPA+DHA concentration lower than 0.3 grams

per 100 grams (such as fresh cod, fresh haddock, fresh sole) (26).

Table 1. Commonly consumed oily and white fish in the National Diet and Nutrition Survey of British adults aged 19 to 64 years during

2000/2001 with corresponding LC n-3 PUFA content.

Type of fish EPA

(gram per 100 grams)

DHA

(gram per 100 grams)

LC n-3 PUFA

(gram per 100 grams)

OILY FISH

Fresh salmon 1.2 1.3 2.7

Canned and smoked salmon 0.55 0.85 1.54

Pickled, smoked and canned sardines and pilchard 1.17 1.20 2.60

Canned sardines 0.55 0.86 1.57

Fresh trout 0.23 0.83 1.15

Herring 0.51 0.69 1.31

Kipper 1.15 1.34 2.49

Fresh tuna 0.3 1.1 1.5

Fresh mackerel 0.71 1.10 1.93

WHITE FISH

Canned tuna 0.06 0.27 0.37

Fresh cod 0.08 0.16 0.25

Fresh haddock 0.05 0.10 0.16

Fresh plaid and whiting 0.16 0.10 0.30

Fresh sole 0 0 0.1

Table adapted from (28). Includes data from MAFF fatty acids supplement to McCance & Widdowson’s The Composition of Foods 1998, and MAFF fish

and fish products, 3rd supplement to McCance & Widdowson’s The Composition of Foods, 1993.

10

ADDITIONAL HEALTH BENEFITS OF FISH: VITAMIN D

Oily fish are also very important dietary sources of vitamin D. Vitamin D is a fat-soluble vitamin which is

essential for the growth and maintenance of healthy bones through increasing dietary calcium absorption

within the body (30). Vitamin D deficiency leads to rickets (brittle bone disease) in children and osteomalacia

(softening of the bones) in adults (31). Taken together with calcium, vitamin D also helps protect older adults

from osteoporosis. There is accumulating evidence that vitamin D has other functions in the body including

modification of cell growth, neuromuscular and immune function and reducing inflammation (31). A low

vitamin D status has also been implicated, but not proven, to be associated with other diseases such as

osteoporosis, cancer (especially colorectal cancer), cardiovascular disease and type 1 diabetes (32-34).

Mammals can synthesize vitamin D themselves from adequate exposure to the sun, and this is the main route

for maintaining adequate levels of vitamin D in the body. Vitamin D is a pro-hormone that can be produced

photochemically: vitamin D3 is produced from 7-dehydrocholesterol in the skin by exposure to sunlight or

ultraviolet light (UVB: wavelength 290-310nm). Vitamin D2 is formed similarly from ergosterol in plants, fungi

and lower life forms. A number of factors can affect the synthesis of vitamin D in the skin including season and

latitude, cloud cover, skin pigmentation and ethnicity, use of sunscreens and clothing and atmospheric

pollution. If there is inadequate vitamin D3 synthesis within the skin, generally caused by limited exposure to

sunlight, then a dietary supply of vitamin D becomes essential.

Vitamin D can also be ingested from the diet, where it exists in two main forms: vitamin D3 (cholecalciferol) in

foods from animal origin, which accounts for most of the vitamin D in the diet; and vitamin D2 (ergocalciferol)

which is found plant foods that have been irradiated with UV light. Overall, very few foods contain vitamin D.

For most people, diet accounts for 10-20% total vitamin D intake with 80-90% coming from cutaneous

synthesis. Among the best dietary sources of vitamin D are oily fish (including salmon, mackerel, herring and

trout) and fish oils, providing up to 20 micrograms of vitamin D per 100 grams (31). Lower amounts of vitamin

D are present in red meat, liver and egg yolks (approximately 1-5 micrograms per 100 grams) (Figure 4).

Vitamin D in these foods and in fish is primarily in the form of vitamin D3 and its metabolite 25(OH)D3 (35).

Before 1995, vitamin D from meat accounted for 1% total dietary vitamin D. Meat contains little native

vitamin D but as better measurement techniques detected more metabolites of vitamin D, which were

considered to be more potent, these have been added to food composition tables (36). The apparent increase

in vitamin D intakes in the British household food data, in 1995 and 1996, is a direct result of including the

potency factor for meat (37), and meat now accounts for 10% or more of the total vitamin D intake in the UK

diet. In the UK, some foodstuffs are also fortified with vitamin D and these include margarines (approximately

7 micrograms per 100 gram). In the UK fortification is mandatory for hard margarines, and manufacturers

11

voluntarily fortify soft margarines. Milk is not routinely fortified in the UK but some breakfast cereals and

powdered milks may be fortified. In other countries there may be fortification of milk and bread. Vitamin D

can also be found in dietary supplements including cod liver oil. A single capsule usually contains 5

micrograms. Supplements used to treat vitamin D deficiency may be cholecalciferol or ergocalciferol.

Figure 4. Intake of vitamin D from different foods in a cohort of 3241 women from Aberdeen. The largest contribution

comes from fish (38%) followed by meat (13%). The vitamin D in the cereal pasta group is coming from fortified breakfast

cereals. The vitamin D in the cakes confectionary is coming from fortified fats used in baking. The fats represent fat spreads

(data obtained from Macdonald HM, 2012)

In the human body, vitamin D3 is metabolised to the active steroid hormone 1,25-dihydroxyvitamin D3 by

successive hydroxylation reactions in the liver and kidney. Vitamin D2 is metabolised to 1,25-dihydroxyvitamin

D2 by the same enzyme systems. 25-hydroxyvitamin D is the main storage form of precursor substrate for

vitamin D and its level in plasma or serum is currently accepted as the best marker of vitamin D status (38).

A significant proportion of the UK population have inadequate vitamin D levels – as defined by a plasma 25-

hydroxyvitamin D concentration of <25 nanomol per liter (39) - especially older children, younger adults, older

institutionalised individuals and infants from black and ethnic minority groups (40). Furthermore, the

incidence of rickets has re-emerged within some sub-groups of the UK population (particularly ethnic

minorities) (41). There is also evidence of greater vitamin D ‘insufficiency’ in Scotland (42). Solar UV radiation

varies with latitude and during the winter at latitudes of 52° and above (i.e. the UK) there is no ultraviolet light

of the appropriate wavelength for the synthesis of vitamin D. A nationwide study of predictors of

hypovitaminosis D (defined as 25(OH)D < 40 nmol/L) in British adults aged 45 found that plasma 25-

hydroxyvitamin D concentrations were higher in participants who either ate oily fish or who took vitamin D

supplements compared to those who did not (42).

12

FISH AS A DIETARY SOURCE OF VITAMIN D

Oily fish has the highest level of vitamin D in foods (Table 2) (43). Fish almost exclusively contains the vitamin

D3 form which appears to be the more effective form both for growth of the fish (44) and for health of the

consumer when given as a large bolus (45;46). Albeit when taken on a daily basis there appears to be no large

difference between vitamin D2 and vitamin D3 efficacy (47). Vitamin D is stored in fat-containing tissues (e.g.

liver and muscle) and so preparation of the product can also alter the levels of vitamin D (48). Thus,

improvements in product processing may also have the potential to improve fish vitamin D levels. However,

with the exception of frying, cooking methods have little effect on vitamin D levels of salmon (49) and

therefore consumption would be expected to contribute to raising vitamin D status.

Table 2. Total vitamin D levels in oily fish

Product Vitamin D

(micrograms per 100 grams)

Raw Herring 19.0

Canned sardines in brine 4.6

Canned sardines in oil 5.0

Raw Salmon 5.9

Canned Salmon 9.2

Raw Mackerel 8.2

Smoked Mackerel 8.0

Data obtained from (36).

Research has highlighted that levels of vitamin D within and between different fish species can vary (50). One

study in the US also found that farmed salmon contained approximately 25% of the vitamin D content of wild

salmon (48) (Table 3). In Atlantic salmon, vitamin D levels in muscle have been shown to be improved by

increasing dietary levels of the vitamin (51). Therefore, the potential exists to further improve the healthiness

of farmed fish through increasing endogenous vitamin D levels. Further research is required to investigate the

seasonal and geographical effects on vitamin D content both within and between different UK landed fish

species. In addition, more research is needed in the use of alternative ingredients for fish feeds incorporating

vitamin D.

13

Table 3. Variations in vitamin D levels in wild and farmed Salmon

Product Vitamin D

(micrograms per 100 gram)

Salmon - fresh and wild caught 15 - 25

Salmon - fresh farmed 2.5 - 6.3

Data obtained from (52).

The vitamin D in fish originates solely from dietary sources as fish are not thought to photosynthesise their

own vitamin D, unlike higher vertebrates (53). Therefore, in wild fish species, vitamin D levels fluctuate

depending on their diet (50) and plankton, which contains high levels of vitamin D (D2 and D3), ultimately

forms the basis of this vitamin in fish. Although the supplementation of vitamin D into aquaculture feeds is

currently not supported under EC regulations (EC directive 1970), the current movement towards utilising

vegetarian alternatives as part replacements for fish meal and oil in fish feeds, although causing no issues in

relation to meeting the vitamin D requirement of the fish, may reduce the health benefits of vitamin-D rich

seafood (54).

The recommended daily intake of vitamin D for human subjects is under constant debate (33). Currently,

there is no recommended intake level of vitamin D in the UK for children over 4 and adults up the age of 65

who receive adequate sunlight exposure as this is assumed to provide sufficient vitamin D status during

summer and allow for stores to be laid down for the winter. However, for those at risk of deficiency (e.g.

individuals confined indoors, or those who are completely covered up when going outside), pregnant and

lactating women, vitamin D intakes of 10 micrograms per day are recommended (Table 4). As pregnant

women are advised to avoid eating large amounts of liver, due to the presence of the vitamin A teratogen, or

eggs, due to the possible presence of listeria, fish becomes an even more important dietary source of vitamin

D. For newborn babies and children up to 3 years old, the daily recommendation is 8.5 micrograms and 7

micrograms, respectively.

Table 4: Current UK Reference Nutrient Intakes (RNI) for vitamin D (micrograms per day)

Age Male Female

0- 6 months 8.5 8.5

7 months - 3 years 7 7

4 years to 65 years 0* 0

65+ years 10 10

Pregnancy - 10

Lactation (0-4 months) - 10

Lactation (4+ months) - 10

*10g/d for individuals at risk of inadequate UVB sunshine exposure. Data obtained from (37;39).

14

In order to make a vitamin D claim, the product must contain a significant amount as laid down in the

regulations. To claim that a product is a source of vitamin D it should contain 15% of the recommended daily

amount (RDA - which is the European equivalent of the UK Reference Nutrient Intake or RNI) in 100g. Or, to

make a high vitamin D claim, the product should contain 30% of the RDA. Within the UK, the RNI for vitamin D

is 10 micrograms per day for the over 65s and those not receiving adequate UVB exposure (see Table 4).

Therefore, it is very likely that a high vitamin D claim could be made for many oily fish products.

REFERENCES

1. The state of world fisheries and aquaculture 2010. 2010. Rome, FAO.

2. Welch AA, Lund E, Amiano P et al. Variability of fish consumption within the 10 European countries participating in

the European Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 2002;5:1273-85.

3. Decker EA, Akoh CC, Wilkes RS. Incorporation of (n-3) fatty acids in foods: challenges and opportunities. J Nutr

2012;142:610S-3S.

4. Hooper L, Thompson RL, Harrison RA et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease,

and cancer: systematic review. BMJ 2006;332:752-60.

5. Wang C, Harris WS, Chung M et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid,

benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J

Clin Nutr 2006;84:5-17.

6. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA

2006;296:1885-99.

7. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:1645S-54S.

8. Harris WS, Ginsberg HN, Arunakul N et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J

Cardiovasc Risk 1997;4:385-91.

9. Pownall HJ, Brauchi D, Kilinc C et al. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with

lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins.

Atherosclerosis 1999;143:285-97.

10. Stalenhoef AF, de Graaf J, Wittekoek ME, Bredie SJ, Demacker PN, Kastelein JJ. The effect of concentrated n-3 fatty

acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients

with hypertriglyceridemia. Atherosclerosis 2000;153:129-38.

11. Bays H. Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J

Cardiol 2006;98:71i-6i.

12. de Roos B, Mavrommatis Y, Brouwer IA. Long-chain n-3 polyunsaturated fatty acids: new insights into mechanisms

relating to inflammation and coronary heart disease. Br J Pharmacol 2009;158:413-28.

13. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary

atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.

14. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on coronary

restenosis, intima-media thickness, and exercise tolerance: a systematic review. Atherosclerosis 2006;184:237-46.

15. Angerer P, Kothny W, Stork S, von Schacky C. Effect of dietary supplementation with omega-3 fatty acids on

progression of atherosclerosis in carotid arteries. Cardiovasc Res 2002;54:183-90.

16. Brouwer IA, Geelen A, Katan MB. n-3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease. Prog Lipid Res

2006;45:357-67.

17. von Schacky C. Omega-3 fatty acids: antiarrhythmic, proarrhythmic or both? Curr Opin Clin Nutr Metab Care

2008;11:94-9.

18. Raitt MH, Connor WE, Morris C et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular

fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-91.

15

19. Leaf A, Albert CM, Josephson M et al. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid

intake. Circulation 2005;112:2762-8.

20. Brouwer IA, Zock PL, Camm AJ et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with

implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA)

randomized trial. JAMA 2006;295:2613-9.

21. Mori TA, Beilin LJ, Burke V, Morris J, Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on

platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997;17:279-86.

22. Hornstra G. Influence of dietary fat type on arterial thrombosis tendency. J Nutr Health Aging 2001;5:160-6.

23. GISSI Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial

infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto

miocardico. Lancet 1999;354:447-55.

24. Harris WS, von SC. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med

2004;39:212-20.

25. von SC. The Omega-3 Index as a risk factor for cardiovascular diseases. Prostaglandins Other Lipid Mediat

2011;96:94-8.

26. Joint FAO/WHO expert consultation on the risks and benefits of fish consumption. 2010. Rome, FAO/WHO. FAO

Fisheries and Aquaculture Report No. 978.

27. Nutritional aspects of cardiovascular disease. Report of the Cardiovascular Review Group Committee on Medical

Aspects of Food Policy. Department of Health. 1994. London, H.M. Stationary Office. Reports on Health and Social

Subjects no. 46.

28. Advice on fish consumption: benefits and risks. 2004. London, Scientific Advisory Committee on Nutrition.

29. Harris WS. International recommendations for consumption of long-chain omega-3 fatty acids. J Cardiovasc Med

(Hagerstown ) 2007;8 Suppl 1:S50-S52.

30. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006;116:2062-72.

31. Dietary reference intakes for Calcium and Vitamin D. Institute of Medicine. 2011. Washington D.C., National

Academies Press.

32. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum

concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84:18-28.

33. Zittermann A, Schleithoff SS, Koerfer R. Putting cardiovascular disease and vitamin D insufficiency into perspective.

Br J Nutr 2005;94:483-92.

34. Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB

Substudy 2 Study Group. Diabetologia 1999;42:51-4.

35. Ovesen L, Brot C, Jakobsen J. Food contents and biological activity of 25-hydroxyvitamin D: a vitamin D metabolite

to be reckoned with? Ann Nutr Metab 2003;47:107-13.

36. The Composition of Food. London: Food Standards Agency, 2002.

37. Nutrition and bone health: with particular reference to Calcium and Vitamin D. Department of Health. No.49. 1998.

London, The Stationary Office.

38. de la Hunty A, Wallace AM, Gibson S, Viljakainen H, Lamberg-Allardt C, Ashwell M. UK Food Standards Agency

Workshop Consensus Report: the choice of method for measuring 25-hydroxyvitamin D to estimate vitamin D

status for the UK National Diet and Nutrition Survey. Br J Nutr 2010;104:612-9.

39. Dietary reference values for food energy and nutrients for the United Kingdom. Department of Health. No. 41.

1991. London, HMSO.

40. Henderson, L., Irving, K., Gregory, J., Bates, C. J., Prentice, A., Perks, J., Swan, G., and Farron, M. National Diet and

Nutrition Survey: adults aged 19-64 years. Volume 3: Vitamin and mineral intake and urinary analytes. TSO. 2003.

London.

41. Callaghan AL, Moy RJ, Booth IW, Debelle G, Shaw NJ. Incidence of symptomatic vitamin D deficiency. Arch Dis Child

2006;91:606-7.

42. Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and

lifestyle predictors. Am J Clin Nutr 2007;85:860-8.

43. Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency an important, common, and easily treatable

cardiovascular risk factor? J Am Coll Cardiol 2008;52:1949-56.

16

44. Barnett BJ, Cho CY, Slinger SJ. Relative biopotency of dietary ergocalciferol and cholecalciferol and the role of and

requirement for vitamin D in rainbow trout (Salmo gairdneri). J Nutr 1982;112:2011-9.

45. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-

hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998;68:854-8.

46. Tripkovic L, Lambert H, Hart K et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-

hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr 2012;95:1357-64.

47. Biancuzzo RM, Young A, Bibuld D et al. Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective

as an oral supplement in maintaining vitamin D status in adults. Am J Clin Nutr 2010;91:1621-6.

48. Lu Z, Chen TC, Zhang A et al. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to

satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol 2007;103:642-4.

49. Chen TC, Chimeh F, Lu Z et al. Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch

Biochem Biophys 2007;460:213-7.

50. Mattila P, Piironen V, Haapala R, Hirvi T, Uusi-Rauva E. Possible Factors Responsible for the High Variation in the

Cholecalciferol Contents of Fish. J Agric Food Chem 1997;45:3891-6.

51. Graff IE, Waagbo R, Fivelstad S, Vermeer C, Lie O, Lundebye AK. A multivariate study on the effects of dietary

vitamin K, vitamin D3 and calcium, and dissolved carbon dioxide on growth, bone minerals, vitamin status and

health performance in smolting Atlantic salmon Salmo salar L. J Fish Dis 2002;25:599-614.

52. Food rich in vitamin D [online]. Nature Systems. 2010. 7-5-2012.

53. Takeuchi A, Okano T, Sayamoto M et al. Tissue distribution of 7-dehydrocholesterol, vitamin D3 and 25-

hydroxyvitamin D3 in several species of fishes. J Nutr Sci Vitaminol (Tokyo) 1986;32:13-22.

54. Bell JG, Waagbo R. Safe and nutritious aquaculture produce: benefits and risks of alternative sustainable aquafeeds.

In: Holmer M, Black K, Duarte CM, Marba N, Karakassis I, eds. Aquaculture in the ecosystem. Berlin: Springer

2008:185-225.