Early vs. late time-restricted feeding: is when we break the fast important for metabolic health?

The prevalence of type 2 diabetes^[1], a metabolic disorder characterized by chronic high blood glucose, insulin insensitivity, and defects in insulin secretion, has been steadily increasing worldwide. The disorder and its associated complications^[2], such as heart disease, diabetic neuropathy, nephropathy, and retinopathy, have significant negative effects on quality of life^[3], and generate substantial economic^[4] costs. Since type 2 diabetes occurs in large part due to excess fat mass, caused by an imbalance between energy intake and output, dietary modification^[5] is a cornerstone of prevention, management, and— as some clinical trials suggest—even remission^[6] of type 2 diabetes.

Intermittent fasting^[7] (IF), an eating pattern that involves recurring periods of little or no energy intake, has become a topic of great research interest as a potential tool for improving aspects of metabolic and immune health, including potential benefits for controlling the risk of type 2 diabetes. There are several ways to fast intermittently, which are depicted in Figure 1. Some studies on time-restricted feeding^[8] (TRF), a form of IF that typically involves a fasting period of 12-21 hours and an eating window of three to 12 hours daily, have reported improvements in glycemic control in both animals^[9] and humans^[10].

One study^[11], which was covered in Study Deep Dives #44, Volume 2, attempted to isolate the effects of TRF from that of weight loss by comparing early TRF (which restricts the feeding window to the earliest part of the waking day) to a typical 12-hour diet. Among other health marker improvements, researchers reported better glycemic control in the TRF condition, even though food intake was matched between conditions and no weight loss occurred. However, since the study didn’t include a “late” TRF group for comparison, it’s not clear if the beneficial effects were the result of TRF per se, or of aligning meals with circadian rhythms^[12], the body’s natural biological clock.

Circadian rhythms are cycles of gene expression, metabolism, and behaviors that are regulated in humans in two ways^[13]: (i) by light, via the suprachiasmatic nucleus (SCN) in the brain, and (ii) by clock proteins that are present in nearly every cell, which cycle within a 24-hour period. Circadian rhythms regulate local metabolic processes^[14], and have evolved to promote certain behaviors and activities during the day (e.g., physical activity, arousal, and eating) or night (e.g., sleep and fasting). This is why it is believed that circadian misalignment^[15] may occur when food consumption happens at an “inappropriate” circadian time, such as late in the evening. In fact, studies have^[16][17] reported impaired glucose tolerance with evening meals as compared to identical meals given in the morning, and this impairment seems to be the result of lower insulin secretion and insulin resistance.

Studies like the ones mentioned above suggest that the human metabolism may be optimized^[18] for food intake during the earlier part of the day when insulin sensitivity, beta cell responsiveness, the thermic effect of food, and other factors depicted in Figure 2 are all higher, compared to the evening. However, tightly-controlled studies examining the effects of consuming food earlier vs. later in the day on glycemic control in humans are currently lacking. The aim of the study under review was to examine the effects of a nine-hour early TRF (TRFe; eating between 8 a.m. and 5 p.m.) or delayed TRF (TRFd; eating between 12 p.m. and 9 p.m.) on glucose tolerance in men at risk for type 2 diabetes.

Early time-restricted feeding (TRFe), a meal timing strategy that restricts the eating window to the daytime portion of the circadian rhythm, is a simple, and possibly useful, dietary intervention for type 2 diabetes. With previous evidence suggesting that early time restricted feeding could be more effective than eating later in the day, the study under review aimed to examine the effects of early (eating between 8 a.m. and 5 p.m.) vs. delayed (eating between 12 p.m. and 9 p.m.) TRF on glucose tolerance in men at risk for type 2 diabetes.