Comprehensive impact of Intermittent Hypoxia Training and Intermittent Fasting on metabolic and cognitive health in adults with obesity: an umbrella systematic review and meta-analysis.

This systematic review and meta-analysis investigated the effects of two non-pharmacological interventions, both individually and in combination, on adults diagnosed with obesity:

1. **Intermittent Hypoxia Training (IHT):** This involves exposing individuals to controlled, reduced oxygen levels, mimicking high-altitude conditions. The typical oxygen levels used in IHT studies range from 10-15% O₂.

2. **Intermittent Fasting (IF):** This encompasses various eating patterns that cycle between periods of eating and voluntary fasting. Examples include the 5:2 diet (eating normally for 5 days, severely restricting calories for 2 non-consecutive days), alternate-day fasting (alternating between days of normal eating and days of severe calorie restriction or complete fasting), and time-restricted feeding (e.g., 16:8, where all daily food intake occurs within an 8-hour window, followed by a 16-hour fast).

The study compared these interventions against control groups (e.g., usual care, no intervention, or a standard diet/exercise regimen) or other interventions, depending on the individual studies included in the meta-analysis.

The researchers measured a comprehensive set of outcomes, categorized into:

**Metabolic Health Markers:**

* **Body Weight:** Changes in overall body mass.

* **Insulin Sensitivity:** The body's ability to respond to insulin, often assessed by measures like fasting insulin levels or the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

* **Glucose Levels:** Fasting blood glucose concentrations.

* **Lipid Profiles:** Levels of various fats in the blood, including:

* Triglycerides (TG)

* Low-density lipoprotein (LDL) cholesterol (often called "bad" cholesterol)

* High-density lipoprotein (HDL) cholesterol (often called "good" cholesterol)

**Cognitive Function:** Specific domains of mental processing, including:

* **Memory:** The ability to encode, store, and retrieve information.

* **Executive Function:** Higher-level cognitive processes like planning, problem-solving, decision-making, and working memory.

* **Attention:** The ability to focus on specific stimuli and sustain concentration.

* **Global Cognition:** Overall cognitive ability, often assessed by general screening tools.

The primary objective was to evaluate how IHT, IF, or their combination impacts these metabolic and cognitive outcomes in adults living with obesity.

This meta-analysis synthesized data from **28 studies**, which collectively included **2,134 participants**.

The population studied consisted of **adults diagnosed with obesity**. Specifically, participants were required to be **aged 18 years and above**, with a **Body Mass Index (BMI) of 30 or higher**, based on World Health Organization (WHO) criteria.

Across the included studies, the participants had a **mean age of 45 ± 12 years**, indicating a broad age range from young to middle-aged adults. The gender distribution was approximately **60% female and 40% male**.

The studies were conducted in various settings, as is typical for a meta-analysis drawing from diverse research.

Crucially, the meta-analysis **excluded studies with participants who had secondary diseases that could confound the outcomes** of IHT and IF. This means individuals with conditions such as diabetes, cardiac conditions, or other severe chronic illnesses were not included in the aggregated data. This exclusion criterion aimed to isolate the effects of IHT and IF specifically on obesity-related metabolic and cognitive issues, rather than on complications from other severe health problems.

The studies included in this meta-analysis used a range of validated tools and standard clinical assessments to measure metabolic and cognitive outcomes.

For **metabolic health outcomes**, the measurements typically involved:

**Body Weight:** Measured using standard scales, with changes calculated from baseline.

**Fasting Glucose Levels:** Blood samples taken after an overnight fast to determine blood sugar concentration.

**Insulin Resistance:** Often assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), which is calculated from fasting glucose and fasting insulin levels. Fasting insulin levels would also be measured from blood samples.

**Lipid Profiles:** Blood samples were analyzed to determine the concentrations of:

* Triglycerides (TG)

* Low-density lipoprotein (LDL) cholesterol

* High-density lipoprotein (HDL) cholesterol

For **cognitive function outcomes**, the studies utilized various **validated neuropsychological tools** designed to assess specific cognitive domains. While the abstract doesn't list every single test used, it provides examples of the types of instruments employed:

**Global Cognition:**

* **Montreal Cognitive Assessment (MoCA):** A widely used screening tool for detecting mild cognitive impairment and dementia. It assesses several cognitive domains, including attention, executive functions, memory, language, visuospatial skills, abstraction, calculation, and orientation. Scores range from 0 to 30, with higher scores indicating better cognitive function.

**Executive Function:**

* **Stroop Test:** This test measures selective attention, cognitive flexibility, and processing speed. Participants are typically asked to name the color of words, where the word itself might be a different color (e.g., the word "blue" printed in red ink). The interference effect (slower response time or more errors when the word and color conflict) is a key measure.

**Memory:**

* **Digit Span Test:** A subtest of many intelligence and memory batteries, it assesses working memory and auditory attention. Participants are asked to recall a sequence of numbers, both forwards and backwards. The longest sequence correctly recalled indicates memory span.

The meta-analysis standardized cognitive outcomes such that **higher scores always indicated better performance**, which is a crucial step for combining data from different studies that might use varied scoring conventions. This allows for a consistent interpretation of effect sizes across the included research.

This study is an **umbrella systematic review and meta-analysis**. This means it systematically identifies, evaluates, and synthesizes evidence from multiple primary research studies (in this case, individual clinical trials and observational studies) to provide a comprehensive overview of the topic. While an "umbrella review" sometimes refers to a review of other systematic reviews, the methods described here indicate a systematic review and meta-analysis of primary studies.

**Study Design of Included Studies:** The meta-analysis included both **randomized controlled trials (RCTs)** and **non-randomized comparative studies**.

**Randomized Controlled Trials (RCTs):** These are considered the gold standard for evaluating interventions. In an RCT, participants are randomly assigned to either an intervention group (e.g., IHT, IF, or combined) or a control group (e.g., no intervention, placebo, or standard care). Randomization helps ensure that groups are comparable at baseline, minimizing the risk of confounding variables influencing the results. This design allows for strong inferences about cause and effect.

**Non-randomized Comparative Studies:** These studies compare outcomes between groups that were not randomly assigned to interventions. While they can provide valuable insights, they are more susceptible to bias because differences between groups might exist from the outset, making it harder to attribute observed effects solely to the intervention.

**Search Strategy and Data Sources:**

The researchers conducted a rigorous search for studies published from **January 2006 to October 2024**. They utilized five major electronic databases:

PubMed

Web of Science

Scopus

Google Scholar

Cochrane Library

Additionally, they searched **gray literature** databases (OpenGrey and the Grey Literature Report) to find studies not typically indexed in commercial databases (e.g., conference proceedings, theses, government reports), aiming to minimize publication bias. Manual searches of reference lists from included studies and relevant review articles were also performed. The search terms combined keywords related to "Intermittent Hypoxia Training," "Intermittent Fasting," "Obesity," "Metabolic Health," and "Cognitive Function."

**Inclusion Criteria for Studies:**

Published in English (a potential limitation).

Involved adult participants (≥18 years) diagnosed with obesity (BMI ≥ 30).

Evaluated IHT, IF, or their combination as primary standalone interventions