Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2009
Publication Date: 8/24/2009
Citation: Ahmad, S.M., Haskell, M.J., Raqib, R., Stephensen, C.B. 2009. Men with Low Vitamin A Stores Respond Adequately to Primary Yellow Fever and Secondary Tetanus Toxoid Vaccination. American Journal of Clinical Nutrition. 138:2276-2283.
Interpretive Summary: The recommended daily allowance of vitamin A has been set by determining the amount needed to prevent nutritional blindness (xerophthalmia). However, we feel that higher levels may be needed to maintain normal immune function. We recruited men with low liver reserves of vitamin A into this study and provided half with high-level supplementation to increase their liver stores. The remaining half received a placebo. Immune function was measured in both groups before and after supplementation and we found that vitamin A increased the number of NK cells, which protect against viral infections and cancer, improved function of phagocytic cells, and decreased inflammation in a manner that may protect against development of some chronic inflammatory diseases.
Technical Abstract: Current recommendations for vitamin A intake and liver stores (20 mg/g) are based on maintaining normal vision. Higher levels may be required for maintaining normal immune function. To test this hypothesis, we conducted an 8 wk residential study among 36 healthy Bangladeshi men with low serum retinol (< 35 mg/dL). Subjects were provided a standard diet and were randomized in a double-blind fashion to receive vitamin A supplementation (a total of 240 mg) or placebo. Vitamin A stores were estimated by isotopic dilution. Liver vitamin A stores for the placebo and intervention groups were 11 ± 8 and 45 ± 12 mg/g, respectively. Significant positive correlations were seen between vitamin A stores and NK-cell number, induced reactive oxygen species production by monocytes, serum IP-10 and LPS-induced TNF-a / IL-10 ratio in whole blood cultures, while significant negative correlations with LPS-induced IL-10 and serum IL-17 were detected. The high vitamin A group had significantly higher serum TNF-a and IP-10 and marginally lower IL-6 levels than the placebo group. Serum IL-6 and IL-17 correlated negatively with vitamin A stores. Two-phase, segmental linear regression identified an inflection point at 20 mg/g in the association between liver vitamin A and indicators of monocyte and granulocyte function. These data indicate that increasing vitamin A stores may marginally improve phagocyte function, increase circulating NK cell numbers and modulate inflammatory responses, although not in a strictly pro-inflammatory or anti-inflammatory manner.