In the Nutritional Prevention of Cancer (NPC) trial in the USA, the Selenium benefit was largely restricted to male smokers with baseline plasma Selenium level below 113 µg/l. The strongest protective effect was against prostate cancer, with a hazard ratio of 0.48 (95% CI: 0.28-0.80) (Duffield-Lillico et al, 2002). None of the subjects had plasma Selenium levels below 60 µg/l and very few were less than 80 µg/l, thus the cohort must be considered Selenium-adequate by current nutritional standards (Combs, 2000).
Although there is a risk in generalising results of individual epidemiological and intervention studies, this result would suggest, using the levels presented by Combs (2001) above, that the vast majority of the world’s population (including that of Australia, with an estimated mean plasma or serum level around 89 µg/l, and many populations in Europe (Rayman, 2000)) would be in the responsive range.
The NPC participants lived in a region where dietary Selenium intake is around 90 µg/d (Clark et al. 1996), thus with the addition of the 200 µg supplement, individuals in the treatment group would have received around 270-310 µg/d. Combs (2001) suggested that a Selenium intake of 200-300 µg/d may be required to significantly reduce cancer risk. This compares with an estimated Australian adult intake of 75 µg/d. Of course, as Rayman (2000) notes, Selenium requirement varies between individuals in the same population. Even Moyad (2002), who expressed doubts about the interpretations of certain Selenium studies, and considers some estimates of its cancer-protective effect to be optimistic, suggested that an intake of 200 µg Selenium/d and around 50 mg vitamin E/d may be beneficial, particularly for current or previous smokers. The results of the NPC trial (Duffield-Lillico et al, 2002) suggested that males may have a higher Selenium requirement than females. Pregnant females may have a higher Selenium requirement than non-pregnant females (Dylewski et al, 2002).
Further studies may find optimum adult Selenium intakes in the range 125-280 µg/d, with means of around 130 (for females) and 230 (for males).[link to Cancer page]
Current mean Selenium intake by Australian adults is estimated to be around 75 µg/d, so there is a large gap for most people between actual and ideal Selenium intake. Likewise, further studies are required to determine optimum Selenium intakes for infants and children, but they are likely to be at least double the current Australian RDIs (listed above).
Further evidence to support these estimates includes:
- Recent studies by John Arthur, the UK’s foremost Selenium researcher, indicate that the activity of various selenoenzymes is not maximised/optimised until a plasma Selenium level of around 100 µg/l is reached.
- “Current evidence…suggests that a plasma level of around 120 µg/l may be optimal for cancer protection, at least against some cancers” (Thomson, 2004). This generally equates to a Selenium intake of at least 105 µg/d for a 70 kg person (Combs, 2001), and in some individuals (under high oxidative stress), up to 200 µg/d.
- In a UK study, participants were supplemented with either placebo, 50 or 100 µg/d Selenium as selenite for 15 weeks. Baseline levels of plasma Selenium were around 80 µg/l. The authors concluded: “The data indicate that these subjects had a functional Selenium deficit with suboptimal immune status and a deficit in viral handling. They also suggest that the additional 100 µg Selenium/d may be insufficient to support optimal function.” (Broome et al, 2004). Thus optimal intake was still not achieved at around 160 µg/d.
- “Information from both animal and human research indicates that 100-200 µg additional Selenium/d are necessary for greatest reduction of cancer…” (Whanger, 2004).
- Reaching an optimum plasma Selenium concentration of around 120 µg/l would require supplemental Selenium of around 100 µg/d for low-baseline-Selenium individuals, in addition to dietary intake of around 75 µg/d (Combs, 2005).
Results of South Australian blood Selenium surveys (Lyons et al, 2004)
Main points:
- 2002 survey (n=288): plasma Selenium 103 µg/l. These were healthy people. High-risk sub-groups likely to be lower.
- Cancer protection target: 120 µg/l.
- Surveys 1977-2002 (n=834): evidence of 1980s decline
- Estimated adult Australian intake: 75 µg/day.
Of course, Selenium is a micronutrient and has a relatively narrow therapeutic index. Chronic selenosis occurs in Enshi County, China where coal-contaminated soil contains up to 8 mg Selenium/kg, and residents have consumed up to 7 mg/d. Common symptoms include nail thickening and cracking and hair loss, and some people exhibit skin lesions (Liu & Li, 1987; Yang & Zhou, 1994). The concern that the incorporation of selenomethionine into body proteins could increase Selenium to toxic levels appears unwarranted because a steady state is established, which prevents the uncontrolled accumulation of Selenium (Schrauzer, 2000).
Combs (2001) considered it probable that the WHO and European Union estimates of the upper safe limit of Selenium intake of 400 and 300 µg/adult/d, respectively, are too conservative. Under normal conditions, a Selenium intake of less than 1,000 µg/d (or 15 µg/kg bodyweight) does not cause toxicity (Neve, 1991; Poirier, 1994; Whanger et al 1996; Taylor, 1997). People living in parts of China, the USA, Venezuela and Greenland have ingested Selenium at this level for their entire lives without ill effects (Taylor, 1997). However, it would be prudent at this stage to limit medium- to long-term Selenium intake to around the US reference dose, which has been set at 350 µg/d for a 70 kg human (Schrauzer, 2000).
Except in the case of certain severe diseases, Selenium intakes in excess of the estimated optimum intakes (130 and 230 µg/d for women and men, respectively) are unlikely to provide further benefit and are not recommended.
The bioavailability of organic Selenium compounds in foods is generally high (apparent absorption of 70-95%), particularly from plant foods, where most Selenium is in the selenomethionine form. Selenite, on the other hand, is more likely to be 60-70% absorbable (Combs & Combs, 1986; Lyons et al, 2003). Selenium in wheat (whether naturally accumulated or biofortified) appears to be highly bioavailable (Meltzer et al, 1992; Djujic et al, 2000).
The food systems of very few countries appear to deliver an optimum level of Selenium to their populations, and indeed the food systems of most countries do not even provide enough Selenium to maximise selenoenzyme expression. The impact of this deficiency and suboptimality in global health terms is difficult to quantify, but is likely to be enormous given the high prevalence of various cancers, cardiovascular diseases, viral diseases (including AIDS, hepatitis, measles and influenza), and exposure to environmental pollutants throughout much of the world. It is thus a matter of urgency that many countries begin to address this major public health issue and develop effective, sustainable ways to increase Selenium intakes (Combs, 2001).
Broome CS, McArdle F, Kyle JAM, Andrews F, Lowe NM, Hart CA, Arthur JA, Jackson MJ 2004. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 80: 154-162.
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Taylor EW 1997. Selenium and viral diseases: facts and hypotheses. J Orthomolec Med 12(4): 227-239.
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Yang GQ, Zhou RH 1994. Further studies on human maximum safe dietary selenium intake and a discussion on some related problems. J Trace Elem Electrol Health Dis 8: 159-165.
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