食素性也：强行改变饮食习惯成为素食者并没有想象的那么健康
近年来，素食已经逐渐成为健康食品的代名词，许多人甚至克制自己成为了完全不沾荤腥的素食者。那么，素食主义真的更健康么？
人类在漫长的进化过程中尝试并且适应了各种各样的食物，多样化的食物来源确保人体能够获得充足的营养。特别是机体无法生成的基本营养物质，如ω6和ω3脂肪酸。体内的脂肪酸去饱和酶（FADS）负责将植物油、鱼、肉的ω6和ω3转化为长链多不饱和脂肪酸，而长链多不饱和脂肪酸承担着重要的生物学功能。FADS基因进化得很快，常常会发生突变并引起严重的问题。既往研究发现一个特殊的FADS2遗传变异，会使FADS2基因出现22bp的插入/缺失。鉴于素食者缺乏肉类来源的长链多不饱和脂肪酸，插入版FADS2可能帮助素食者更有效地代谢长链多不饱和脂肪酸前体。
2016年7月，牛津大学出版社旗下《分子生物学与进化》第33卷第7期正式发表康奈尔大学、印度浦那大学、堪萨斯大学的研究报告。该研究收集了印度素食者和美国杂食者的血样，用PCR和DNA测序分析FADS2上的插入和缺失。
结果发现，素食者几乎都携带插入版FADS2，缺失版FADS2则极为罕见。携带两个拷贝插入变异的素食者（I/I）远多于杂食者，杂食者约有一半携带两个拷贝的缺失变异（D/D）。
随后，该研究对千人基因组计划的数据进行分析，发现I/I基因型的比例在非洲和南亚最高，在欧洲和东亚比较低。进一步研究表明，插入版FADS2是祖先传下来的，尼安德特人（主要分布在欧洲、西亚、北非）和丹尼索瓦人（主要分布在北亚、东亚）都携带这种等位基因。
那么，FADS2是否真能影响个体的长链多不饱和脂肪酸生产。该研究分析了志愿者血液中的脂肪水平，证实插入版FADS2的携带者能够更好地把植物油转化为ω-6长链多不饱和脂肪酸。在消耗等量植物油的情况下，携带插入版FADS2的志愿者体内累积了最多的ω-6花生四烯酸。已知这种花生四烯酸有促进炎症的作用。
更糟糕的是，由于插入版FADS2让转化机器忙于花生四烯酸生产，机体内抗炎症的ω-3脂肪酸（EPA和DHA）显著减少。ω-6和ω-3长链多不饱和脂肪酸的这种失衡会带来严重的健康问题。虽然ω-6是必不可少的营养物质，但这种物质过多并没有什么好处。
因此，强行改变饮食习惯成为素食者并没有想象的那么健康。
Mol Biol Evol. 2016 Jul;33(7):1726-39.
Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid.
Kothapalli KS, Ye K, Gadgil MS, Carlson SE, O'Brien KO, Zhang JY, Park HG, Ojukwu K, Zou J, Hyon SS, Joshi KS, Gu Z, Keinan A, Brenna JT.
Cornell University; University of Pune, Pune, India; The University of Kansas.
Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product-precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.
KEYWORDS: arachidonic acid; fatty acid desaturases; indel (insertion–deletion); long chain polyunsaturated fatty acids; population divergence.; positive selection
PMID: 27188529
PMCID: PMC4915354
DOI: 10.1093/molbev/msw049
