Zoe hails personalized nutrition trial success, results come under scrutiny

The researchers from the UK-based personalized nutrition firm compared the impact of the program to general advice provided on cardiometabolic health in 347 participants over 18 weeks.

Primary outcome results published in the journal Nature Medicine showed a significant reduction in triglycerides (TGs) in comparison to the control group, however differences in low-density lipoprotein cholesterol were insignificant.

For the researchers, the results were positive thanks to secondary outcomes such as improvements in body weight, waist circumference, microbiome diversity and quality of life scores, leading them to conclude that a personalized nutrition program that addresses metabolic heterogeneity is effective in improving cardiometabolic health in generally healthy individuals.

Personalized diets Zoe promotes its personalized nutrition program based on biological, phenotypic and lifestyle factors for improving adherence and efficacy in comparison to non-personalized advice.

Launched in 2017, the consumer data-focused brand uses stool testing kits, continual glucose monitors, daily diet diaries and lifestyle questionnaires to provide gut health-focused nutrition advice.

While some observational research supports personalized nutrition, randomized controlled trials assessing its efficacy compared to standard dietary advice are still lacking.

Study detailsThe Zoe study randomly assigned participants between the ages of 41 and 70 to either the PDP (n = 177) or control (n = 170) groups.

The PDP used food characteristics, individual postprandial glucose and TG responses to foods, microbiomes and health history, to produce personalized food scores, while the control group received standard care dietary advice (based on the U.S. Department of Agriculture Guidelines for Americans, 2020–2025) using online resources, check-ins, video lessons and a leaflet.

Blood chemistry baseline samples were used as baseline measure for each participant. At 18 weeks, the primary outcomes, serum low-density lipoprotein cholesterol and TG concentrations were measured. Secondary outcomes measured included body weight, waist circumference, glycated hemoglobin (HbA1c), diet quality (HEI score), hip circumference and blood pressure as well as insulin, glucose, C-peptide, apolipoproteins A1 and B, and postprandial TG levels.

Comparisons between the groups at 18 weeks showed reductions in TG concentration in the PDP group. Secondary outcomes showed improvements including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) in the PDP group, and particularly in the ‘highly adherent PDP participants’.

However, there were insignificant or null differences in low-density lipoprotein cholesterol, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs between groups.

Quality of life Zoe has placed emphasis on the study’s quality of life outcomes.

“Crucially, those doing Zoe felt better,” the brand posted on LinkedIn. “They were twice as likely to report improved mood and less hunger and four times more likely to report better sleep and more energy than the control group.”

On average, a greater proportion of PDP participants reported improvements in energy level (43% versus 11%), sleep quality (35% versus 9%), general mood (33% versus 15%) and reduced hunger levels (22% versus 14%) compared with controls.

Under scrutiny Reacting to the study findings, Dr. Nicola Guess, an academic dietitian and researcher at the University of Oxford, published a blog opinion which argued the methodology would have biased the results.

“Their big USP is that people have distinct metabolic responses to food—differences which are driven largely by their microbiome—and that we need diets personalized to this individual biology to get better health,” she wrote. “However the Zoe Method trial did not test whether their novel ‘biologically-driven’ personalized advice was better than generic healthy eating advice.

“They tested whether the Zoe program, with all its support, self-monitoring, education and other bells and whistles was better than a leaflet on generic healthy eating advice and a few emails.”

As an example of one of the ways the PDP was unfairly primed for better results, she noted that only the intervention group was asked to input in real-time everything they ate on at least four occasions each month.

“Think about if a doctor or a dietician asks you to record everything you eat, as you are about to eat it,” she said. “Would that make you pause when you go for that second cookie?”

She also noted that the participants were not blinded and those in the intervention group were wearing continual glucose monitors, which acted as a constant reminder they were being analyzed.

“Why does this matter? Because people who know they are receiving the new cutting edge science-based program are likely to believe they will feel better and get better outcomes. (We call this an expectation of efficacy, and it causes performance bias),” she added.

The blog was posted on LinkedIn, leading to a crowd of commentary with many agreeing that the methodology was flawed and some arguing the results didn’t warrant the cost of the service.

One LinkedIn user posted: “A 2.5kg weight loss (0.15 kg/week) and fall in #triglycerides over 4 months but no change #LDLcholesterol, A standard low-calorie diet would be expected to result in a 0.5-1kg weekly weight loss.”

Another noted: “It reads as somewhat of an own-goal for Zoe who had a unique opportunity to test a much-sought-after hypothesis yet missed the mark and failed to deliver.”

One LinkedIn user posted a cost comparison between the Zoe PDP and the British National Health Service’s (NHS) publicly-funded healthcare system on LinkedIn.

They wrote: “The key analysis to be done is kg lost per £ invested. If Zoe is £700/patient/year then it is £280 per kg lost…

“For the NHS national diabetes prevention program, average weight loss is 2-4kg/patient depending on the provider though costs are closer to £200/patient, so £50-100 per kg lost”.

Journal: Nature Medicine
doi: 10.1038/s41591-024-02951-6
“Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial”
Authors: Bermingham, K. et al.