The Paleolithic diet and chronic disease risk: a GRADE-assessed systematic review and dose-response meta-analysis of prospective cohort studies and randomized controlled trials

This systematic review and meta-analysis evaluate the effects of the Paleolithic diet on cardiometabolic parameters and chronic disease outcomes by combining evidence from interventional and observational studies. We analyzed 19 randomized controlled trials (RCTs) and 12 prospective cohort studies identified through systematic searches. Both random-effects and fixed-effects meta-analyses, along with dose-response evaluations, were conducted for cohort studies. A fixed-effects model was applied when fewer than five comparisons were available to ensure model stability with limited data. Meta-analysis of RCTs demonstrated significant improvements in cardiometabolic markers including, fasting insulin [Weighted Mean Differences (WMD −1.01 [−1.45, −0.57], <i>p</i> &lt; 0.001], total cholesterol (WMD −0.15, [−0.24, −0.07], <i>p</i> &lt; 0.001), low-density lipoprotein cholesterol (WMD −0.24, [−0.40, −0.08], <i>p</i> = 0.003), triglycerides (WMD −0.16, [−0.24, −0.08], <i>p</i> &lt; 0.001), body weight (WMD −1.74, [−2.57, −0.91], <i>p</i> &lt; 0.001), body mass index (WMD −1.12, [−1.42, −0.82], <i>p</i> &lt; 0.001), and diastolic blood pressure (WMD −3.28, [−4.55, −2.01], <i>p</i> &lt; 0.001). Cohort studies revealed 10% lower all-cause mortality risk (RR: 0.90, 95% CI: 0.87–0.94, <i>p</i> &lt; 0.001), 10% reduced cancer mortality (RR: 0.90, 95% CI: 0.85–0.97, <i>p</i> = 0.004), and 16% lower coronary heart disease incidence (RR: 0.84, 95% CI: 0.70–1.00, <i>p</i> = 0.05) among high adherers. The Paleolithic diet may provide significant benefits for cardiometabolic health and potentially lower the risk of chronic disease.

本系统评价与荟萃分析通过整合干预性与观察性研究证据，评估了旧石器饮食法（Paleolithic diet）对心血管代谢参数及慢性疾病转归的影响。本研究通过系统检索共纳入19项随机对照试验（randomized controlled trials, RCTs）与12项前瞻性队列研究进行分析。针对队列研究，本研究同时采用随机效应模型与固定效应模型开展荟萃分析，并进行剂量反应评估；当可用对照数少于5项时，为保证有限数据下的模型稳定性，采用固定效应模型。随机对照试验的荟萃分析结果显示，多项心血管代谢标志物得到显著改善，包括空腹胰岛素[加权均数差（Weighted Mean Differences, WMD）=−1.01，95%置信区间：−1.45~−0.57，p<0.001]、总胆固醇（WMD=−0.15，95%置信区间：−0.24~−0.07，p<0.001）、低密度脂蛋白胆固醇（WMD=−0.24，95%置信区间：−0.40~−0.08，p=0.003）、甘油三酯（WMD=−0.16，95%置信区间：−0.24~−0.08，p<0.001）、体质量（WMD=−1.74，95%置信区间：−2.57~−0.91，p<0.001）、体质量指数（WMD=−1.12，95%置信区间：−1.42~−0.82，p<0.001）及舒张压（WMD=−3.28，95%置信区间：−4.55~−2.01，p<0.001）。队列研究结果显示，在高依从旧石器饮食法的人群中，全因死亡风险降低10%[相对风险（Relative Risk, RR）=0.90，95%置信区间：0.87~0.94，p<0.001]，癌症死亡风险降低10%（RR=0.90，95%置信区间：0.85~0.97，p=0.004），冠心病发病风险降低16%（RR=0.84，95%置信区间：0.70~1.00，p=0.05）。旧石器饮食法或可对心血管代谢健康产生显著益处，并有可能降低慢性疾病的发病风险。