Weight loss in midlife linked to lower mortality

Excess body weight in middle age is one of the main drivers of diseases of aging: type 2 diabetes, coronary heart disease and stroke, some types of cancer, osteoarthritis, COPD, etc. Even 5-10% weight gain at the age of 40-50 significantly shifts metabolic markers into the "red zone". At the same time, it is during this period that there is still a "window of plasticity": lifestyle changes take hold relatively well and can affect the trajectory of health for decades.

What is already known

Weight loss improves blood pressure, lipids, glycemia, and inflammatory markers, as confirmed by randomized trials of behavioral programs. But the issue of “hard” long-term outcomes (first major chronic disease, all-cause mortality) has long been controversial: observations were short, samples were specific (for example, only people with diabetes), and weight loss itself was often “confounded” with unintentional weight loss due to hidden diseases.

People who lost weight from “overweight” (BMI ≥ 25) to “healthy” (BMI < 25) at age 40–50 and maintained it were less likely to develop serious illnesses decades later and lived longer on average than their peers who remained overweight. The effect was demonstrated in three large cohorts followed to age 35–47. The study was published in JAMA Network Open.

What did they do?

The researchers analyzed three independent cohorts (23,149 participants in total) with repeated height/weight measurements and associated BMI trajectories at 40–50 years with health outcomes:

• Whitehall II (UK): median follow-up 22.8 years; assessed first major chronic disease (type 2 diabetes, heart attack, stroke, cancer, asthma/COPD).
• Finnish Public Sector (Finland): median 12.2 years; same outcomes.
• Helsinki Businessmen Study (Finland): median age 35; assessed overall mortality.

Participants were divided into 4 groups over two consecutive visits: stable healthy weight; reduction from BMI ≥ 25 to < 25; gain from < 25 to ≥ 25; stable overweight. An important detail: we are talking about non-surgical and non-drug weight loss, i.e., essentially, about lifestyle.

What did they find?

Compared to people who remained overweight:

• Reducing to a healthy BMI in midlife was associated with a lower risk of a first chronic disease:
  • Whitehall II: HR 0.52 (95% CI 0.35–0.78).
  • The effect persisted even after excluding diabetes from the composite outcome: HR 0.58 (0.37–0.90).
  • FPS: HR 0.43 (0.29–0.66); after excluding diabetes, HR 0.70 (0.62–0.79).
• In HBS, this weight trajectory was associated with lower all-cause mortality: HR 0.81 (0.68–0.96) over ~35 years of follow-up.
• In contrast, gaining weight from normal to overweight increased the risks, and maintaining a stable “healthy” weight throughout life remained the best strategy.

Why is this important?

The long-term benefits of "behavioural" weight loss - beyond diabetes prevention - have long been controversial due to short-term follow-ups and confounding with unintentional weight loss due to illness. Here:

• observations lasted for decades (which is critical for outcomes like heart attack/mortality);
• included relatively healthy middle-aged people, in whom weight loss was more likely to be intentional;
• The results were reproduced in three independent samples.

Bottom line: Even moderate and sustained weight loss in midlife is associated with lower risks of major diseases and lower mortality—and not just through diabetes prevention.

Important Disclaimers

• These are observational data - they show association, not causation.
• There were no labels for "intentional" vs. "unintentional" weight loss (although the design reduces the risk of this confusion).
• Some measurements in one of the cohorts were self-reported.
• Participants are mainly of European origin; generalizability to other populations requires testing.

What can we take away from this in practice?

• The best thing is not to gain weight: maintaining a BMI < 25 from adolescence remains optimal.
• If you're already overweight, losing and maintaining it into a healthy range in your 40s and 50s seems like a worthwhile investment—the potential benefits extend beyond diabetes.
• It's not necessarily about radical weight loss: many clinical benefits begin with a sustained 5-10% weight loss through nutrition, movement, sleep, and stress management.