Time Restricted Feeding Also Benefits Healthy Individuals

I have been writing lately regarding the benefits to time restricted feeding, which includes diets such as alternate day fasting, as relates to overweight or obese individuals or in individuals with other related metabolic disorders.

For example look over these posts:




However, in this post I wanted to review a previous manuscript published in the prestigious journal, Cell Metabolism, that demonstrated the benefits of time restricted feeding, specifically alternate day fasting, to otherwise healthy individuals:


The results published in this manuscript were derived from a randomized controlled trial carried out over the course of four weeks and involved a strict adherence to an alternate day fasting (ADF) protocol where the trial participants were healthy, middle-aged humans. The results demonstrated that this type of diet improved markers of general health while causing a 37% calorie reduction on average. Importantly, no adverse effects occurred even after more than 6 months.

The study was designed so as to monitor cardiovascular parameters, such as heart rate, blood pressure, cholesterol levels, cardiovascular disease (CVD) risk, body composition, and the metabolome and proteome of the participants. In addition, the study assessed both the effectiveness and safety of this type of time restricted feeding diet. All parameters were examined at the end of the 4-week study and again at least 6 months later. Control participants were matched for age, sex, and parameters of health but did not adhere to the strict alternate days of fasting.

1. By definition the metabolome refers to the complete set of small-molecules (amino acids, lipids, carbohydrates, etc.) found within a biological sample where the sample can refer to specific cells, or cellular organelle, or an organ, for example.
2. By definition the proteome represents the complete set of proteins found within a biological sample where the sample can refer to specific cells, or cellular organelle, or an organ, for example.

Some of the benefits, in the short term, for alternate day fasting were found to be an improvement in overall fat distribution and cardiovascular health as well as a lowering of level of circulating thyroid hormone, when compared with the control participants.

Some of the benefits, in the long term, identified in this study were reduced levels of circulating total cholesterol, low density lipoprotein (LDL: the "so-called" bad cholesterol), very low-density lipoprotein (VLDL), and triglycerides compared to the control group. The levels of high-density lipoprotein (HDL: the "so-called good cholesterol) was similar in both groups. When heart rates were compared the alternate day fasting participants were lower.

Red blood cell (RBC) counts, hematocrit, hemoglobin, iron, and transferrin saturation levels were lower in fasting participants than in the control participants, but even so these parameters remained within the normal reference ranges.

Examination of the metabolome, found that of 113 detected metabolites, 54 were significantly modified metabolites and were at least 20% higher after 36 hours of fasting. The majority of these 54 metabolites were lipids or free fatty acids, including polyunsaturated fatty acids (PUFA) and a form of vitamin E. It is not surprising that fasting individuals have higher serum free fatty acids (FFA) since the conditions of the diet (fasting) triggers fatty acids to be released from their site of storage, adipose tissue (fat). Conversely, 49 metabolites were at least 20% lower, consisting mainly (44.9%) of amino acids or related metabolites (e.g., ornithine and citrulline). Of potential significance to lower amino acid levels in the circulation is that reduced methionine has been correlated to lead to lifespan extension in non-human model organisms. Several short-chain FFA and lipids were also found to be downregulated such as propionic acid (C3:0) and nonanoic acid (C9:0) which are associated with intestinal bacterial metabolism.

When the proteomes of fasting participants were compared to controls there were over 2,000 significantly modulated proteins with the majority of these being downregulated within 36 hours of diet onset. These proteins are involved in pathways related to lipid metabolism (i.e., lipid transport, lipoprotein, and steroid-binding processes), pathways related to energy metabolism (i.e., mitochondrial fatty acid oxidation, glycogen metabolism, and TCA cycle),
and stress responses.

Not all measures of health are affected by the alternate day fasting protocol as evidenced by the fact that fasting participants and control participants showed no differences in bone mass and white blood cell counts as well as the levels of various other immune cell types.

There are plenty of studies that demonstrate that periodic food intake interacts with circadian rhythms at the transcriptional, metabolic, and microbial levels and these changes manifest with numerous health benefits in unhealthy individuals but, as demonstrated in this manuscript, healthy individuals as well. Not all individuals will manifest with the same level of health benefit from periods of recurring fasting and outcomes may depend on the desired effect and parameters measured as well as being subject to individual differences.

TAKE HOME: This study used a time restricted diet that consisted of fasting every other day but there are benefits to other forms of time restricted feeding. As a means to lose weight, improve cardiovascular health, as well as many other parameters that define health, one should consider making the effort to adhere to an alternate day fasting regimen.

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