Medicinal Foods and Obesity

The prevalence of obesity has markedly increased over the past three decades and is now a major international public health challenge. Worldwide, more than 1.9 billion adults (39%) are overweight, and >650 million adults (13%) are obese. ¹ The problem is rapidly extending to the next generation, ² with more than a 400% increase among children and adolescents since 1975. ¹ Obesity is now on the rise in low- and middle-income countries, although the prevalence remains highest in high-income nations. In the United States, for example, prevalence of obesity is 37.7% of the adult population or nearly threefold higher than the international average. ³ Unfortunately, low- and middle-income countries are on a trajectory to catch up to these unenviable figures in the coming decades.

Multiple large studies demonstrate that obesity reduces lifespan, ^{4 –8} with a predicted loss of 9–13 years of life for individuals with body mass index (BMI) >35 kg/m². ⁴ The Global BMI Mortality Collaboration recently reported data from 10.6 million participants followed an average of 14 years >239 large studies, including 189 studies that included 4 million participants who were never smokers ⁸ ; the data demonstrate a 31% increase in risk of premature death for every 5 BMI unit increase >25 kg/m², and an overall increased risk of 45% for stage 1 obesity, 94% for stage 2 obesity, and ∼3-fold for stage 3 obesity. ⁸ In many ways, obesity is a model of premature aging, as it is characterized by early onset of multiple age-related diseases; caloric excess relative to biological need does accelerate aging, ⁹ and many of the nine identified hallmarks of biological aging ¹⁰ are accelerated by obesity. ⁹

Obesity increases the risk of comorbidities, including cardiovascular disease, type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and some cancers. ^11,12 The risk of obesity-related comorbidities increases with increasing BMI; for example, there is an estimated 27% increase in risk of coronary heart disease and 18% increase in risk of stroke for each 5 kg/m² elevation in BMI. ¹³ In addition to disproportionately affecting minority populations, obesity has a disproportionate adverse health impact on blacks and Hispanics, ^14,15 and the outcomes of weight loss trials in these populations are less successful than in white participants. ¹⁶

Modest reductions in BMI resulting from as little as 5–10% weight loss significantly reduce the risk and severity of obesity comorbidities, with continued improvement with greater weight loss. ^12,17 Lifestyle intervention focused on reducing caloric intake and increasing caloric expenditure is, appropriately, the first-line approach to obesity management. Unfortunately, however, although short-term weight loss frequently occurs, long-term adherence is generally poor. Consequently, weight regain after weight loss is common, and obesity reversal through lifestyle intervention alone rarely exhibits sustained success. Accordingly, development of adjunct approaches to diet and exercise to achieve sustained weight reduction is critical. Broadly, these approaches may include pharmacotherapy, alterations in dietary pattern or composition, medicinal foods, and bioactive food components and supplements.

Although there are now six approved agents for weight management, with four approved in the past decade, ^{18 –20} pharmacological management of obesity has not yet been able to deliver safe effective sustained weight management, and clinical adoption of these agents is thus far minimal. The number needed to treat to achieve >5% weight loss ranges from 4–5 for the newer pharmacological agents to 10–12 for Orlistat, ¹⁹ whereas the number needed to harm, as defined by adverse medication effects likely to prompt discontinuation, ranges from 4 to 6 for three of the available agents. ¹⁹ In short, currently available weight management medications are clearly not up to the task and both health care providers and consumers are seeking safe effective alternatives. Accordingly, exploration of the role of diet composition, medicinal foods, and bioactive constituents of foods in managing obesity and/or associated comorbidities is increasingly important to both consumers and health care providers.

In this special issue of the journal, preclinical studies demonstrating novel effects of food bioactives on obesity and obesity comorbidities in preclinical animal models (Almedia et al.; Gutman et al.; Gonzalez-Garibay et al.; Ramirez-Higuera et al; Lee et al.) present important opportunities for clinical development. A number of novel food-derived bioactives have advanced to human study and clinical validation in this issue. Murugesan et al. expand upon their recent findings that the citrus flavonoid naringenin promotes conversion of human white adipose tissue to a brown/beige phenotype ²¹ with a new first-in-human study demonstrating that naringenin safely increased thermogenesis and insulin sensitivity and reduced body weight (Murugesan et al.); although these new observations are limited to a careful case report, the consistency of the observations with previous preclinical findings provides encouraging justification for randomized controlled trials on naringenin. This issue also includes randomized trials of dietary patterns (Petrisko et al.) and bioactives (Petrisko et al.; Cazzola et al.; Tunstall et al.; de Silva et al.) in both adults and children. Some of these offer encouraging findings, whereas others are well-conducted trials with substantially negative results, providing much needed guidance to redirect resources for future trials.

We need all the tools we can find to address the obesity epidemic, and medicinal foods and food-derived bioactives will find their place alongside pharmaceutical approaches. Neither will provide complete solutions, but instead offer the opportunity to lower the bar and finally enable successful application of lifestyle modifications to which they must serve as adjuncts.