Food environment as driver for ketogenic diet and possible consequences for kidney health

Obesity, metabolic syndrome and resulting cardiovascular and kidney diseases are growing public health threats, driven by low quality diets. Although these chronic diseases most commonly affect adults, they have their roots in dietary patterns established in adolescence and early adulthood. To combat rising rates of obesity and metabolic syndrome young adults embrace extreme macro nutrient diets characterized by very low carbohydrate and high fat and protein intake, often dubbed the ‘ketogenic diet’. The ketogenic diet pattern severely restricts carbohydrate intake to less than 30 grams per day and shifts metabolism towards fatty acid oxidation and ketone production as an energy source. Most ketogenic diets are based on very high protein intake to achieve adequate energy need sand to prevent reduction of muscle mass.  Short-term studies demonstrating promise for rapid weight loss have created a culture of social acceptability of “eating keto”, likely promoted by marketing and product availability in the food environment (stores, retail outlets, restaurants). Especially young adults in Generation X or the Millennial generation are attracted to the ketogenic diet.

The long-term effectiveness of the ketogenic diet is controversial. Possible harmful biologic consequences,such as effects on kidney injury and function, are poorly understood. Human physiologic studies demonstrate predictable increases in renal plasma flow and glomerular filtration rate in response to high protein diets. Presumably, this compensation (hyperfiltration) is a mechanism to ensure removal of nitrogenous wastes derived from protein. Hyperfiltration is a well-known described mechanism of renal injury in other settings, such as early diabetic nephropathy or after loss of kidney mass due to nephrectomy or recurrent ureteral reflux.Whether hyperfiltration in response to “eating keto” results in kidney damage has not been proven, however many clinicians advise against high protein diets in chronic kidney disease for this reason. New panels of kidney injury markers now allow for short term ‘read-out’ variables that could suggest kidney-related harm from the ‘keto diet’ that is not currently recognized.

There is growing evidence that the built environment plays a critical role in dietary patterns and obesity (Glonti et al,2016, Mackenbach et al, 2014), but (to our knowledge) nothing is known about the environmental mechanisms that play a role in supporting a ‘keto culture’.  Diet culture and obesity are embedded in complex systems (Rutter, 2018) that include individual, social, environmental,and cultural contexts. Our study will, for the first time, collect baseline behavioral and environmental data to provide some new insights into the etiology of this culture and advance new hypotheses for further study.

Even in light of potential harms, the ‘keto’ diet is widely embraced. A wide range of factors interact with uptake and maintenance of ‘specialty’ diets but these have been poorly explored in relation to “keto hype”.  In Aim 2, we will compare individual's expectations of consuming a ketogenic diet with the measured outcomes in our 2-week feeding trial and in Aim 3 of this study will explore the psychosocial factors driving keto uptake in young people, including age, gender,home food / neighborhood food environment, dietary trends, peer influence,social media and lifestyle aspirations amongst young people. Altogether thorough evaluation of unique keto safety concerns and factors driving ‘keto’ uptake in young adults of the Generation X and Millennial Generation will provide evidence to balance ‘keto’ misinformation and marketing. 

We propose a mixed method study combining qualitative interviews with food behavior surveys and store audits combined with a clinical feeding trial to assess the effect of consuming a keto diet on kidney health.

Aim1: Evaluate the kidney-related safety of short-term, healthful ketogenic diet in young, overweight adults.  After baseline measures are taken, 10 participants(male and female, mildly overweight (BMI 25-30), 20-30 year adults living in the C’ville region) without major chronic conditions including diabetes,kidney, cardiac, or liver disease will receive an isocaloric, high protein and low carbohydrate diet for 2 weeks. Each participant consumes one meal daily in the Diet and Nutrition (DAN) laboratory metabolic kitchen and receives the remainder of the daily food allocation packed out to consume at home.Plate-waste method and NDS-R software will be used to measure food consumption(all served and packed-out foods and all uneaten and returned portions will be weighed).  Weight, blood pressure and symptom surveys will be monitored 3 times a week and fasting blood and urine samples performed at baseline and the end of each week to assess compliance to the diet (urinary nitrogen). Differences in estimated glomerular filtrationrate (GFR) determined from serum creatinine and cystatin C will be evaluated for each participant to assess magnitude of increase in GFR on the ketogenic diet. Over the past decade new panels of biomarkers have become available measuring glomerular permeability (urine albumin to creatinine ratio) and kidney injury and repair (urine IL-18, kidney injury molecule 1 [KIM-1], neutrophilgelatinase-associated lipocalin [NGAL], liver fatty acid type binding protein[L-FABP], tumor necrosis factor α [TNF-α], human cartilage glycoprotein 39[YKL-40], and monocyte chemoattractant protein 1 [MCP-1]). Changes in selected markers will be assessed as indicators of kidney injury comparing week 2 assessments to baseline values.

Aim 2: Compare anticipated vs. actual benefits of the ketogenic diet on weight andw ell-being. Many young adults have unrealistic expectations about the benefits of the ketogenic diet driven by fad diet marketing and social media. In this qualitative component we will performing in-depth interviews and surveys of participants in Aim 1 prior to beginning feeding to allow probing for their treatment expectations around weight loss and well-being/symptomatology and sources of information about the ketogenic diet.  Additional interviews and surveys will be completed after subjects completed the 2 weeks of feeding.  We will discuss the individual's achieved results and probe for concordance with expectations, adequacy of information, and media portrayal of the ketogenic diet from participants perspectives.

Aim 3: Explore the role of psychosocial and environmental drivers of the “keto hype”

We will design and conduct a behavioral survey to better understand the drivers of  “keto hype” including: a) interpersonal factors driving uptake (e.g. lifestyle trends, perceptions of the diet,demographics and psychological factors (mood, depression, perceptions of body image, hedonic aspects etc); b) the interpersonal factors (i.e. the social environment) including interactions with peers, social media, family, and c)the settings associated with keto diet uptake including keto products (and marketing) available in the food environment (home, school, university, work)and food cues (e.g. product aesthetics, other contextual factors).  Our survey will target young people who subscribe to the diet to explore the role of the food environment in keto diet uptake. This survey will be conducted via Mechanical Turk (MTurk),targeting 100 participants aged 20 – 30 who undertake a keto diet. In addition,we will conduct some ‘on-the-ground’ data collection targeting food outlets in the Charlottesville metropolitan area to determine the proportion and price difference of “keto friendly” compared to “normal” products available in a variety of food outlets (grocery stores, gas stations, restaurants) using undergraduate / graduate students.  We will design a new environmental audit tool to carry out this research.  In addition, we will conduct store exit interviews with young people using the stores to identify how food cues are influencing food patterns and diet uptake (e.g. product aesthetics, affective contextual signals).  This data will provide new insights into keto-related aspects of the food environment and allow for the generation of new hypotheses for further study in this area.