In Reply Dr Portillo-Sanchez and colleagues have pointed to limitations in our study1 that, although previously discussed in the main article, are important enough to merit extra discussion. These limitations include sample size, dropout rate in the alternate-day fasting group, and (mostly) metabolically healthy trial participants. Dr Portillo-Sanchez and colleagues express concern that these limitations threaten the validity of the study results—that is, that alternate-day fasting does not produce superior adherence, weight loss, weight loss maintenance, or cardioprotection vs daily calorie restriction.1 Our sample size was somewhat limited, so we may not have been able to detect small but clinically meaningful differential change in our chosen outcome measures. However, we reemphasize that many individuals assigned to follow alternate-day fasting instead followed de facto daily calorie restriction throughout the trial: these individuals consumed substantially more energy than prescribed on “fast days” and substantially less energy than prescribed on “feast days” (shown in Figure 2 in the article).1 Moreover, average weight loss differed by less than 1 kg between the intervention groups throughout most of the year (shown in Figure 3 in the main article).1 It therefore seems unlikely that our main study results1 were largely influenced by sample size, especially because our power calculation required fewer than 30 participants to detect an expected 5% body weight difference between the alternate-day fasting group and daily calorie restriction group. The dropout rate in the alternate-day fasting group (38%) was high, and more participants in this group withdrew owing to dissatisfaction with diet compared with those in the daily calorie restriction group.1 People who withdraw from obesity intervention trials may do so because of lack of significant weight loss,2 so our study results1 may have been biased in favor of alternate-day fasting. But if so, this would not threaten our conclusion that alternate-day fasting was found to not be superior to daily calorie restriction in changing our outcome measures.1 Finally, many of our participants could be classified as being “metabolically healthy” according to several proposed criteria.3 In response to moderate weight loss, people with this phenotype tend not to experience much improvement in the cardiovascular disease risk indicators measured in our study.4 Therefore, it remains an open question as to whether alternate-day fasting or daily calorie restriction produces superior cardioprotection in people who are metabolically healthy to begin with. It has been shown that 2 diet therapies that result in similar weight loss can nonetheless produce differential improvement in markers of glucose and lipid homeostasis in obese, insulin-resistant adults.5 This is highly relevant, because preliminary evidence deriving mostly from rodent studies suggests that alternate-day fasting may result in benefits on glucose and lipid homeostasis that are distinct from those observed in response to daily calorie restriction.6

中文翻译：

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女性也使用 5α-还原酶抑制剂

在回复中，Portillo-Sanchez 博士及其同事指出了我们研究中的局限性，尽管之前在主要文章中进行了讨论，但这些局限性非常重要，值得额外讨论。这些限制包括样本量、隔日禁食组的退出率以及（主要是）代谢健康的试验参与者。Portillo-Sanchez 博士及其同事表示担心这些限制会威胁研究结果的有效性——也就是说，与每日卡路里限制相比，隔日禁食不会产生更好的依从性、体重减轻、体重减轻维持或心脏保护作用。1 我们的样本规模有限，因此我们可能无法在我们选择的结果测量中检测到微小但具有临床意义的差异变化。然而，隔日禁食组的退出率 (38%) 较高，与每日卡路里限制组相比，该组中有更多参与者因对饮食不满意而退出。 1 退出肥胖干预试验的人可能会这样做由于缺乏显着的体重减轻2，因此我们的研究结果 1 可能偏向于隔日禁食。但如果是这样，这不会威胁到我们的结论，即发现隔日禁食在改变我们的结果测量方面并不优于每日卡路里限制。 1 最后，根据多项研究，我们的许多参与者可以归类为“代谢健康”。建议的标准。 3 针对中度体重减轻，具有这种表型的人在我们的研究中测量的心血管疾病风险指标往往不会有太大改善。 4 因此，隔日禁食或每日卡路里限制是否对代谢健康的人产生更好的心脏保护作用仍然是一个悬而未决的问题。首先。已经表明，导致类似体重减轻的 2 种饮食疗法仍然可以对肥胖、胰岛素抵抗的成年人的葡萄糖和脂质体内平衡标志物产生不同的改善。 5 这是高度相关的，因为主要来自啮齿动物研究的初步证据表明，隔日禁食可能对葡萄糖和脂质体内平衡产生益处，这与观察到的每日卡路里限制不同。6 隔日禁食或每日卡路里限制是否会对代谢健康的人产生更好的心脏保护作用，这仍然是一个悬而未决的问题。已经表明，导致类似体重减轻的 2 种饮食疗法仍然可以对肥胖、胰岛素抵抗的成年人的葡萄糖和脂质体内平衡标志物产生不同的改善。 5 这是高度相关的，因为主要来自啮齿动物研究的初步证据表明，隔日禁食可能对葡萄糖和脂质体内平衡产生益处，这与观察到的每日卡路里限制不同。6 隔日禁食或每日卡路里限制是否会对代谢健康的人产生更好的心脏保护作用，这仍然是一个悬而未决的问题。已经表明，导致类似体重减轻的 2 种饮食疗法仍然可以对肥胖、胰岛素抵抗的成年人的葡萄糖和脂质体内平衡标志物产生不同的改善。 5 这是高度相关的，因为主要来自啮齿动物研究的初步证据表明，隔日禁食可能对葡萄糖和脂质体内平衡产生益处，这与观察到的每日卡路里限制不同。6