Taking Blue Zones with a grain of salt

• Blue Zones, a Netflix docuseries, discusses the lifestyle endemic in five areas in the world where people are significantly more likely to live longer and disease-free compared to the rest of us.?
• It highlights physical exercise, nutrition, recovery, and emotional well-being as the primary drivers of longevity.?
• Not all conclusions, however, outlined in the docuseries should be considered equally valid as they may result from the “healthy-participant” bias.

Living a long and healthy life has undeniably become one of the most sought-after life goals of the modern upper class. For those fortunate enough to have secured financial freedom and comfort, the primary focus now is the pursuit of longevity. To this end, individuals are willing to try almost anything, irrespective of its scientific validation, and as human nature usually dictates, the easier the solution, the more attractive it becomes. In their relentless pursuit of myriad, so-called bio-optimization treatments are employed with varying degrees of scientific validation, giving way to a booming longevity economy and room for “snake oil” products. Recently, however, as a response to the growing dogma that “the more complex, elusive, and expensive the longevity treatment is, the better it should be,” Blue Zones, a Netflix original docuseries, presents a pure antithesis. The docuseries covers the habits and lifestyle of individuals located in five unrelated places worldwide where individuals live significantly more and disease-free without employing any advanced bio-optimization treatments today’s biohackers spend tens of thousands on. The docuseries’ main point is that a long and healthy life is a consequence of simple but fundamental habits that touch upon nutrition, physical exercise, recovery, and mental and emotional health.

Pillars of Longevity according to Blue Zones. It’s not news.?

Blue Zones’ depiction of how simple lifestyle changes can yield a massive impact on one’s longevity is truly captivating. The most astonishing revelation of this docu-series is that there are common characteristics among the people living in these five areas that are critical determinants of longevity. This common denominator is that people exercise regularly, nourish their bodies with healthy, non-obesogenic food, sleep and recover properly, and maintain close interpersonal connections and a sense of purpose in life. Moreover, the fact that the fundamental elements of longevity are present in all five areas despite their disparate nature across every domain, including geography, culture, and ethnicity, proves their strength as longevity predictors. The fact that these factors can coexist in a society that is so different is genuinely remarkable. However, these factors’ impact on longevity is certainly not news for the world of science. These four factors are the most scientifically established predictors of longevity, with each one being supported by ample evidence from longitudinal studies.??

Taking Blue Zones with a grain of salt?

Longevity is one of the hardest things to track. The reason is that you need to follow someone throughout their entire life, record all possible exogenous confounders (i.e., environmental factors that may impact longevity), measure their impact, and account for potential genetic predispositions that one may have. Such a complex set of relationships requires a Randomized Control Trial (RTC), which in science constitutes the gold standard for making scientific observations. An RTC requires subjects to be confined in an environment where all possible confounders are controlled, with each experiment exposing a set of subjects to a measurable factor that is hypothesized to produce a significant change in the variable measured (i.e., length and quality of life) and benchmarking the outcome against a group of people who are also confined in the same environment but are not subjected to this factor. Although this type of experiment is possible under certain circumstances (i.e., testing the efficacy of a drug), it is undoubtedly fictitious when measuring longevity, as it would require locking people in a lab for the rest of their lives.

Understanding the foundations of scientific studies

Longevity, however, wasn’t the first thing science aimed to quantify and wasn’t able to do through an RTC. An RTC cannot measure many long-term phenomena (i.e., weight loss). In such cases, scientists resort to epidemiological or observational studies. Such experiments involve tracking individuals in free-living conditions over long periods while exposing them to the factor we hypothesize impacts the measurable variable. The fact that individuals are not confined in a lab allows for all possible confounders to interfere with the variable we want to measure, and as a result, in the case of epidemiological studies, the burden of proof is much more significant. In other words, due to a myriad of confounders that may impact the result, for an epidemiological study to produce meaningful results, it must analyze a significant number of individuals and showcase that the controlled variable (i.e., the factor that is hypothesized to produce change) results in truly bing changes. To assess the strength of the results produced from an epidemiological study, Sir Bradford Hill, a renowned scientist of the 20th century, proposed a set of frameworks that looked into the twelve attributes of the research and its results.

The Bradford Hill criteria, also known as Hill’s criteria for causation, are principles used to assess the likelihood of a causal relationship between an exposure and an outcome. These criteria were proposed by the British epidemiologist Sir Austin Bradford Hill in 1965.

The Bradford Hill criteria include the following factors to consider when determining causation:

• Strength of association: A strong association between the exposure and outcome increases the likelihood of a causal relationship.
• Consistency: The relationship between the exposure and outcome should be consistently observed in different studies and populations.
• Specificity: A specific exposure should lead to a specific outcome.
• Temporality: The exposure should precede the outcome in time.
• Biological gradient: There should be a dose-response relationship, meaning that higher levels of exposure should result in a higher likelihood of the outcome.
• Plausibility: The relationship should be biologically plausible based on existing knowledge and scientific understanding.
• Coherence: The relationship should be consistent with known facts and not contradict other established scientific evidence.
• Experimental evidence: Experimental studies, such as randomized controlled trials, can provide stronger evidence for causation.
• Analogy: If similar exposures have been shown to cause similar outcomes, it strengthens the likelihood of a causal relationship.

It is important to note that the Bradford Hill criteria are not definitive proof of causation but rather a set of guidelines used to evaluate the strength of evidence for a causal relationship.

This framework can be used to invalidate a significant number of epidemiological studies conducted over the years. In his work, a famous Stanford University professor, John Ioannidis, claimed that most observational studies produced misleading results. Ioannidis is particularly well-known for his 2005 paper titled “Why Most Published Research Findings Are False,” which discusses the limitations and potential biases in scientific research, especially in the context of observational studies. A famous example is the wine study, which famously proposed that drinking one glass of wine every week improves cardiovascular health and lowers the likelihood of mortality and morbidity. The same experiment was repeated and failed to produce the same results. Apart from failing to fulfill many of the principles proposed by the framework, this study also suffers from the so-called “healthy participant” bias, a common weakness of most epidemiological studies that fail the reproducibility test. The “healthy-participant” bias is the simple concept that when you are testing a relatively healthy habit, for example, drinking one glass of wine per week vs. three or more” participants who are likely to adhere to that are most likely already healthy thanks to their adherence to other healthy habits such as exercising and eating healthy. If this is the case, then these people consuming one glass of wine per week is not the determining factor for improved health.?

Although the docuseries Blue Zones touches upon several attributes of human biology that have been extensively proven to be beneficial to our health, it also runs wild by jumping to conclusions that certain specific behaviors, endemic to some of these areas, are determinants of longevity. Some of them were that the wine of Ikaria makes people live longer or its climate can cure lung cancer.?

Let’s not miss the big picture.

The main objective of this docu-series was to record the common denominators driving longevity in some parts of the world. Undeniably, the fact that its conclusions are almost identical to what decades of scientific research have independently shown is a powerful argument that longevity is indeed a factor of simple lifestyle choices that include daily movement, healthy nutrition, proper recovery, and emotional well-being. However, “reading into” some isolated behaviors that may also coexist in the lives of those abiding by those four pillars can be dangerous as it may lead one to think that these isolated behaviors are indeed longevity drivers when, in fact, they may have irrelevant or even adverse effects. This is especially true in a world prone to purposefully conflating causation with correlation to profit and create trends.