On 2014 Nov 25, Harri Hemila commented:

Novotny JA, 2012 studied vitamin E kinetics and proposed that the requirement for vitamin E may be lower than previously assumed. However, the study was restricted to just 12 healthy participants who were on average 27 years old. It is not obvious that the metabolism of vitamin E remains constant over the life span, and over various lifestyle and health conditions. Furthermore, the study of concentrations and half-lives teaches us little if anything about the relationship between doses and clinical effects.

In clinical outcomes, the effects of vitamin E depend on age and lifestyle conditions. In the large-scale ATBC Study with 29,133 participants, the effects of 50 mg/day vitamin E on common cold incidence diverged at about 65 years Hemilä H, 2006, DOI. Vitamin E had no effect on younger people, but depending on the smoking level and residential neighborhood, it decreased or increased the incidence of colds in the older participants. Furthermore, vitamin E decreased pneumonia risk by 69% in men who had the least exposure to smoking and exercised during their leisure time, but increased pneumonia risk by 79% in those who had the highest exposure to smoking and did not exercise, whereas vitamin E did not differ from the placebo in the remaining participants Hemilä H, 2011, DOI. Apart from smoking and exercise, the effect of vitamin E on pneumonia risk was also modified by weight and dietary vitamin C intake Hemilä H, 2008, DOI. Finally, among the ATBC Study participants with a dietary vitamin C intake above the median, vitamin E increased mortality by 19% in those aged 50–62 years, whereas it decreased mortality by 41% in those aged 66–69 years Hemilä H, 2009, DOI. For each of these three clinical outcomes very strong statistical evidence showed that the effect of vitamin E supplementation was heterogeneous over the ATBC Study participants.

Median dietary vitamin E intake in the ATBC Study, Anonymous, 1994 was 10 mg/day. Although the abovementioned analyses indicate that some subpopulations benefit from vitamin E in doses higher than the median intake, the ATBC Study does not teach us about dose dependency in those subpopulations. Similarly, there were harmful effects in other subpopulations, but here too we do not know at which dose levels the harm started to appear since only one level of vitamin E supplementation was used.

Nevertheless, the substantial heterogeneity in the effects of the constant dose vitamin E supplementation on the clinical outcomes indicates that its metabolism probably varies by the same factors that modify its effects on clinical outcomes. Therefore, Novotny et al.s kinetic findings with 12 young adults should not be extrapolated to the whole adult population, over all ages and over all diverse lifestyle conditions.

Novotny et al. assume that a vitamin E plasma concentration of 12 μmol/L is ideal, and they estimate that a dietary intake of 4 mg/day may be sufficient to maintain such a plasma concentration in all adults. However, Novotny et al. do not present any evidence that 12 μmol/L is the ideal level for clinically relevant outcomes. As described above, the ATBC Study indicates that some subpopulations may benefit from additional vitamin E even though their median dietary intake was 10 mg/day. Therefore, 4 mg/day is insufficient for them if the abovementioned clinical outcomes are used as the basis for evaluating the best doses of vitamin E. Although the ATBC Study analyses do not teach us what the ideal doses of vitamin E are, they indicate that there cannot be a single best dose for all adults. Thus, the significant heterogeneity in the effects of vitamin E on clinical outcomes indicates that estimating a single recommended dose for all adult people may be ill advised.

On 2014 Nov 25, Harri Hemila commented:

Novotny JA, 2012 studied vitamin E kinetics and proposed that the requirement for vitamin E may be lower than previously assumed. However, the study was restricted to just 12 healthy participants who were on average 27 years old. It is not obvious that the metabolism of vitamin E remains constant over the life span, and over various lifestyle and health conditions. Furthermore, the study of concentrations and half-lives teaches us little if anything about the relationship between doses and clinical effects.

In clinical outcomes, the effects of vitamin E depend on age and lifestyle conditions. In the large-scale ATBC Study with 29,133 participants, the effects of 50 mg/day vitamin E on common cold incidence diverged at about 65 years Hemilä H, 2006, DOI. Vitamin E had no effect on younger people, but depending on the smoking level and residential neighborhood, it decreased or increased the incidence of colds in the older participants. Furthermore, vitamin E decreased pneumonia risk by 69% in men who had the least exposure to smoking and exercised during their leisure time, but increased pneumonia risk by 79% in those who had the highest exposure to smoking and did not exercise, whereas vitamin E did not differ from the placebo in the remaining participants Hemilä H, 2011, DOI. Apart from smoking and exercise, the effect of vitamin E on pneumonia risk was also modified by weight and dietary vitamin C intake Hemilä H, 2008, DOI. Finally, among the ATBC Study participants with a dietary vitamin C intake above the median, vitamin E increased mortality by 19% in those aged 50–62 years, whereas it decreased mortality by 41% in those aged 66–69 years Hemilä H, 2009, DOI. For each of these three clinical outcomes very strong statistical evidence showed that the effect of vitamin E supplementation was heterogeneous over the ATBC Study participants.

Median dietary vitamin E intake in the ATBC Study, Anonymous, 1994 was 10 mg/day. Although the abovementioned analyses indicate that some subpopulations benefit from vitamin E in doses higher than the median intake, the ATBC Study does not teach us about dose dependency in those subpopulations. Similarly, there were harmful effects in other subpopulations, but here too we do not know at which dose levels the harm started to appear since only one level of vitamin E supplementation was used.

Nevertheless, the substantial heterogeneity in the effects of the constant dose vitamin E supplementation on the clinical outcomes indicates that its metabolism probably varies by the same factors that modify its effects on clinical outcomes. Therefore, Novotny et al.s kinetic findings with 12 young adults should not be extrapolated to the whole adult population, over all ages and over all diverse lifestyle conditions.

Novotny et al. assume that a vitamin E plasma concentration of 12 μmol/L is ideal, and they estimate that a dietary intake of 4 mg/day may be sufficient to maintain such a plasma concentration in all adults. However, Novotny et al. do not present any evidence that 12 μmol/L is the ideal level for clinically relevant outcomes. As described above, the ATBC Study indicates that some subpopulations may benefit from additional vitamin E even though their median dietary intake was 10 mg/day. Therefore, 4 mg/day is insufficient for them if the abovementioned clinical outcomes are used as the basis for evaluating the best doses of vitamin E. Although the ATBC Study analyses do not teach us what the ideal doses of vitamin E are, they indicate that there cannot be a single best dose for all adults. Thus, the significant heterogeneity in the effects of vitamin E on clinical outcomes indicates that estimating a single recommended dose for all adult people may be ill advised.