Serum measures of docosahexaenoic acid (DHA) synthesis underestimates whole body DHA synthesis in male and female mice

Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of
higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are
reported to be low, and have not been directly compared between sexes. Here, we apply a new
compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female
C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA,
eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δ 13 C)-n-3 PUFA for four
weeks, followed by high δ 13 C-n-3 PUFA for eight weeks (n=4 per diet, time point, sex). Following
the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels
and δ 13 C were determined and fit to one-phase exponential decay modeling. Hepatic DHA
synthesis rates were not different (P>.05) between sexes. However, n-3 docosapentaenoic acid
(DPAn-3) synthesis from dietary EPA was 66% higher (P<.05) in males compared to females,
suggesting higher synthesis downstream of DPAn-3 in females. Estimates of percent conversion
of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but
severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken
together, our data indicates that reports of low human DHA synthesis rates may be inaccurate,
with synthesis being much higher than previously believed. Future animal studies and
translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis
and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary
DHA recommendations set by health agencies.