Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
J Nutr Biochem. 2024 Sep;131:109689. doi: 10.1016/j.jnutbio.2024.109689. Epub 2024 Jun 12.
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 (δC)-n-3 PUFA for four weeks, followed by high δC-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 δC 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.
女性血液中的二十二碳六烯酸 (DHA) 水平高于男性，这被认为是由于从 α-亚麻酸 (ALA) 合成 DHA 的速率较高所致。然而，DHA 的合成速率据报道较低，且尚未在两性之间进行直接比较。在这里，我们应用一种新的化合物特异性同位素分析模型来确定雄性和雌性小鼠中 n-3 多不饱和脂肪酸 (PUFA) 的合成速率，并评估其在人类群体中的潜在转化。雄性和雌性 C57BL/6N 小鼠被分配到三种 12 周饮食干预中的一种，分别添加 ALA、二十碳五烯酸 (EPA) 或 DHA。这些饮食包括前四周低碳-13（δC）-n-3 PUFA，随后是高 δC-n-3 PUFA 八周（每组饮食、时间点、性别各 4 只）。在饮食切换后，在多个时间点采集血液和组织，并测定脂肪酸水平和 δC，并拟合单相指数衰减模型。雄性和雌性之间的肝 DHA 合成速率没有差异（P＞.05）。然而，与雌性相比，膳食 EPA 衍生的 n-3 二十二碳五烯酸 (DPAn-3) 合成率高出 66%（P＜.05），这表明雌性体内 DPAn-3 下游的合成率更高。膳食 ALA 转化为血清 DHA 的估计百分比为 0.2%，与之前的啮齿动物和人类估计值一致，但严重低估了膳食 ALA 转化为全身 DHA 的 9.5%。总的来说，我们的数据表明，关于人类 DHA 合成率低的报告可能不准确，合成率远高于之前的估计。未来需要进行更多的动物研究，并将该模型转化为人类，以更好地了解 n-3 PUFA 的合成和代谢，以及高于预期的 ALA 衍生 DHA 是否可以抵消健康机构设定的膳食 DHA 推荐量。
