Chapter 1: The Relationship Between Caloric Intake and Aging

Caloric intake plays a critical role in our health, particularly as we age. Previous discussions have addressed various fasting methods and their implications on aging and health (spoiler: it's a complex topic). We now turn our attention to calorie restriction (CR) specifically. (Spoiler: this topic is also nuanced.)

While limiting eating windows—through fasting—can indeed help in maintaining a calorie deficit, it's essential to note that consuming an excessive number of calories in a short timeframe will still lead to weight gain.

Moderate calorie restriction is a well-documented method that has shown promise in extending lifespan across various animal studies. However, this evidence is not without its critics. For example:

• Many studies contrast calorie-restricted animals with a control group that indulges in high-calorie junk food, which can skew results. This often leads to the control group experiencing obesity and age-related health issues.
• Certain genetic makeups respond better to calorie restriction than others. Some animals with specific gene variants may even see a decrease in lifespan when subjected to calorie-restricted diets that benefit others.
• Human randomized controlled trials on calorie restriction are limited and often challenging to conduct.

As noted in a recent review, CR is not yet ready to be recommended as a long-term dietary strategy for healthy individuals, especially the elderly, or those on multiple medications with existing health issues. Nonetheless, one could argue that individuals maintaining a normal BMI in today's obesogenic environment may be practicing some form of self-imposed calorie restriction. While CR remains a promising area of research for healthy aging, there is still much to uncover.

A significant human study examining calorie restriction is the CALERIE study, which included three pilot studies (CALERIE 1) followed by a two-year study (CALERIE 2). (Refer to my earlier post on calorie restriction for more details.)

In summary, there are benefits (such as fat loss, improved cardiovascular markers, and reduced inflammation) as well as drawbacks (like adherence challenges, potential mental health declines, reduced bone density, and minor lean tissue loss).

The gut microbiome's response to calorie restriction warrants attention.

Section 1.1: The Gut Microbiome's Reaction to Dieting

A recent study adds another layer of caution regarding significant calorie deficits: the impact on the gut microbiome.

This human intervention study involved 80 post-menopausal women with varying degrees of obesity. Over 16 weeks, one group followed a medically supervised very low-calorie diet (800 kcal), primarily composed of nutrient shakes, while the other group maintained their weight.

Regular stool samples were collected throughout the study—scientists certainly make sacrifices for research!

As expected, the intervention group lost weight. However, their gut microbiome also underwent changes, exhibiting a reduction in certain microbial species post-diet.

To confirm and expand upon their findings, researchers transferred the stool samples to mice raised in sterile environments.

Key findings: 1. Weight loss occurred in the mice. 2. The dieting process made the microbiome "hungry." The bacteria adapted to less incoming food by modifying their metabolism to extract more nutrients for themselves rather than for their host, which impeded nutrient absorption in the intestines. 3. The dieting phase increased the prevalence of Clostridioides difficile within the gut microbiome. Certain strains of this bacterium can cause serious health issues, including diarrhea and life-threatening colitis, although many individuals carry it asymptomatically.

The cause of the rise in C. difficile remains unclear. However, the authors propose that lower levels of secondary bile salts—produced during fat metabolism—may allow this bacterium to flourish in a low-calorie, low-fat diet.

To summarize: These findings underscore the significance of diet-microbiome interactions in regulating energy balance and highlight the necessity of understanding dietary roles in the balance between harmful and beneficial microbes.

Does this imply that dieting is inherently negative? Not at all. Losing excess weight and maintaining a healthy body weight are generally advantageous.

This study, however, offers insights on how to minimize potential issues associated with very low-calorie diets, especially in scenarios where rapid weight loss is required (e.g., pre-surgery). Considerations include:

• Prioritizing nutrient-dense foods (an essential yet often overlooked point).
• Including healthy fats in your diet.
• Considering prebiotics and probiotics.
• Listening to your body's signals (monitoring for signs of inflammation, diarrhea, etc.).

It’s crucial to avoid starving your gut microbiome, even while dieting.

Chapter 2: Videos on Diet and Microbiome

In this video, "The Impact of Diet & Gut Microbiota in Determining Response & Immune-Related Adverse Events (IRAEs)," experts discuss how dietary choices affect gut health and immune responses.

The second video, "Eating for Two: Nourishing Yourself and Your Gut Microbiome," emphasizes the importance of diet in maintaining a healthy gut microbiome.

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