30
and neck cancer patients was associated with increased cancer recurrence in the first
3.5 years of follow-up (Bairati et al. 2005), and meta-analysis has suggested an
increase in all-cause mortality after high-dose vitamin E supplementation (Miller
et al. 2005). Toxicity has also been associated with consumption of supplemental
vitamin A and its provitamin carotenoid precursors. Excess vitamin A supplementation has been suggested to be associated with adverse effects on bone health, including low bone mineral density and increased fracture risk (Melhus et al. 1998). In
addition, women consuming large amounts of vitamin A supplements during pregnancy have been reported to have increased incidence of congenital abnormalities
(Rothman et al. 1995). There is also a case report of intrahepatic cholestasis in a
patient with chronic hypervitaminosis A after 12 years of supplement consumption,
which resolved after supplements were ceased (Ramanathan et al. 2010). Toxicity
can arise from excess consumption of minerals as well as vitamins. In particular,
there is an increased risk of hyperchromatosis, an iron storage disease associated
with liver injury after excess consumption of iron or multimineral supplements
(Barton et al. 2006).
3.7.2 Fish Oil and Omega-3 Fatty Acids as Supplements
Omega-3 fatty acids are essential fatty acids that cannot be synthesized de novo in
humans and therefore must be provided through the diet (Spector and Kim 2015). A
link between fish oil and ischemic heart disease was suggested by a widely publicized study from 1971 involving Eskimos (Greenlanders) from the west coast of
Greenland (Bang et al. 1971). Greenlanders eating a traditional meat and fish diet
rich in polyunsaturated omega-3 fatty acids had significantly lower levels of plasma
total lipids, plasma cholesterol, plasma triglycerides, and pre β-lipoprotein (equaling very low-density lipoprotein) than both Danes and Greenlanders living in
Denmark. The authors hypothesized that this diet contributed to the low incidence
of ischemic heart disease and diabetes among Greenlanders. Since then, polyunsaturated omega-3 fatty acids taken in the form of fish oils, krill oil, or mixtures of
docosahexaenoic and eicosapentaenoic acids, also known as DHA and EPA, purified from fish oils have become widely used dietary supplements. These fatty acids
have metabolites with anti-inflammatory properties and have electrical stabilizing
effects on ion channels in cardiac myocytes (Sierra et al. 2004; Leaf et al. 2008).
They have been linked to anti-cancer and cardio-protective effects (Gogos et al.
2000; Harris and Isley 2001). However, the therapeutic benefits on cardiovascular
diseases are still controversial owing to disparate findings from different clinical
trials (Glück and Alter 2016). It appears that fish oil and omega-3 fatty acids are
well tolerated, even at doses of 1000–2000 mg/day, and there is little evidence of
toxicity. However, simultaneous consumption of fish liver oils that also contain vitamin A and multivitamin supplements could result in hypervitaminosis
A. Furthermore, fish oils and omega-3 fatty acid supplements may exacerbate
S. Hassan et al.
and neck cancer patients was associated with increased cancer recurrence in the first
3.5 years of follow-up (Bairati et al. 2005), and meta-analysis has suggested an
increase in all-cause mortality after high-dose vitamin E supplementation (Miller
et al. 2005). Toxicity has also been associated with consumption of supplemental
vitamin A and its provitamin carotenoid precursors. Excess vitamin A supplementation has been suggested to be associated with adverse effects on bone health, including low bone mineral density and increased fracture risk (Melhus et al. 1998). In
addition, women consuming large amounts of vitamin A supplements during pregnancy have been reported to have increased incidence of congenital abnormalities
(Rothman et al. 1995). There is also a case report of intrahepatic cholestasis in a
patient with chronic hypervitaminosis A after 12 years of supplement consumption,
which resolved after supplements were ceased (Ramanathan et al. 2010). Toxicity
can arise from excess consumption of minerals as well as vitamins. In particular,
there is an increased risk of hyperchromatosis, an iron storage disease associated
with liver injury after excess consumption of iron or multimineral supplements
(Barton et al. 2006).
3.7.2 Fish Oil and Omega-3 Fatty Acids as Supplements
Omega-3 fatty acids are essential fatty acids that cannot be synthesized de novo in
humans and therefore must be provided through the diet (Spector and Kim 2015). A
link between fish oil and ischemic heart disease was suggested by a widely publicized study from 1971 involving Eskimos (Greenlanders) from the west coast of
Greenland (Bang et al. 1971). Greenlanders eating a traditional meat and fish diet
rich in polyunsaturated omega-3 fatty acids had significantly lower levels of plasma
total lipids, plasma cholesterol, plasma triglycerides, and pre β-lipoprotein (equaling very low-density lipoprotein) than both Danes and Greenlanders living in
Denmark. The authors hypothesized that this diet contributed to the low incidence
of ischemic heart disease and diabetes among Greenlanders. Since then, polyunsaturated omega-3 fatty acids taken in the form of fish oils, krill oil, or mixtures of
docosahexaenoic and eicosapentaenoic acids, also known as DHA and EPA, purified from fish oils have become widely used dietary supplements. These fatty acids
have metabolites with anti-inflammatory properties and have electrical stabilizing
effects on ion channels in cardiac myocytes (Sierra et al. 2004; Leaf et al. 2008).
They have been linked to anti-cancer and cardio-protective effects (Gogos et al.
2000; Harris and Isley 2001). However, the therapeutic benefits on cardiovascular
diseases are still controversial owing to disparate findings from different clinical
trials (Glück and Alter 2016). It appears that fish oil and omega-3 fatty acids are
well tolerated, even at doses of 1000–2000 mg/day, and there is little evidence of
toxicity. However, simultaneous consumption of fish liver oils that also contain vitamin A and multivitamin supplements could result in hypervitaminosis
A. Furthermore, fish oils and omega-3 fatty acid supplements may exacerbate
S. Hassan et al.