Current Role at Stanford


Associate Director, Nutrition Studies Group

Supervisors


All Publications


  • Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS). BMC medicine Dwaraka, V. B., Aronica, L., Carreras-Gallo, N., Robinson, J. L., Hennings, T., Carter, M. M., Corley, M. J., Lin, A., Turner, L., Smith, R., Mendez, T. L., Went, H., Ebel, E. R., Sonnenburg, E. D., Sonnenburg, J. L., Gardner, C. D. 2024; 22 (1): 301

    Abstract

    Geroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes.This study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts.Distinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways.This study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation.Clinicaltrials.gov identifier: NCT05297825.

    View details for DOI 10.1186/s12916-024-03513-w

    View details for PubMedID 39069614

    View details for PubMedCentralID 4306469

  • Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial. JAMA network open Landry, M. J., Ward, C. P., Cunanan, K. M., Durand, L. R., Perelman, D., Robinson, J. L., Hennings, T., Koh, L., Dant, C., Zeitlin, A., Ebel, E. R., Sonnenburg, E. D., Sonnenburg, J. L., Gardner, C. D. 2023; 6 (11): e2344457

    Abstract

    Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.ClinicalTrials.gov Identifier: NCT05297825.

    View details for DOI 10.1001/jamanetworkopen.2023.44457

    View details for PubMedID 38032644

  • Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet. Gut microbes Wastyk, H. C., Perelman, D., Topf, M., Fragiadakis, G. K., Robinson, J. L., Sonnenburg, J. L., Gardner, C. D., Sonnenburg, E. D. 2023; 15 (1): 2178794

    Abstract

    An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.

    View details for DOI 10.1080/19490976.2023.2178794

    View details for PubMedID 36803658

  • SWAP-MEAT Athlete (study with appetizing plant-food, meat eating alternatives trial) - investigating the impact of three different diets on recreational athletic performance: a randomized crossover trial. Nutrition journal Roberts, A. K., Busque, V., Robinson, J. L., Landry, M. J., Gardner, C. D. 2022; 21 (1): 69

    Abstract

    BACKGROUND: Plant-based diets are known to be beneficial for cardiovascular health and promote environmental sustainability. However, many athletes avoid plant-based diets due to concerns of protein inadequacy.OBJECTIVES: To investigate the impact of two predominately plant-based diets-whole food plant-based (WFPB) and plant-based meat alternatives (PBMA)-vs. an omnivorous diet, favoring red meat and poultry (Animal), on endurance and muscular strength.METHODS: 12 recreational runners and 12 resistance trainers were assigned to three diets-WFPB, PBMA, and Animal-for 4weeks each, in random order. Primary outcomes for runners (12-minute timed run) and resistance trainers (composite machine strength) were collected at baseline and after diets, along with secondary performance outcomes and dietary data.RESULTS: 22 recreational athletes completed the study (age: 26.2±4.4years; sex: 10 female, 12 male; BMI: 23.1±2.4kg/m2). Mean differences in 12-minute timed run - WFPB vs. Animal (-23.4m; 95% CI: -107 to 60.0m) and PBMA vs. Animal (-2.9m; 95% CI: -119 to 113m) - were not significant. Mean percent differences in composite machine strength - WFPB vs. Animal (-2.7%; 95% CI: -5.8 to 0.4% and PBMA vs. Animal (-0.7%; 95% CI: -3.5 to 2.2%) - were not significant. Average protein intake for all diets met International Society for Sports Nutrition recommendations.CONCLUSIONS: Our findings suggest recreational athletes can maintain athletic performance on both an omnivorous diet and two diets that are predominately plant-based.TRIAL REGISTRATION: NCT05472701. Retrospectively registered.

    View details for DOI 10.1186/s12937-022-00820-x

    View details for PubMedID 36384651

  • Effect of a Ketogenic Diet versus Mediterranean Diet on HbA1c in Individuals with Prediabetes and Type 2 Diabetes Mellitus: the Interventional Keto-Med Randomized Crossover Trial. The American journal of clinical nutrition Gardner, C. D., Landry, M. J., Perelman, D., Petlura, C., Durand, L. R., Aronica, L., Crimarco, A., Cunanan, K. M., Chang, A., Dant, C. C., Robinson, J. L., Kim, S. H. 2022

    Abstract

    Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes (T2DM), especially between low-carbohydrate options.To compare two low-carbohydrate diets with 3 key similarities (incorporate non-starchy vegetables and avoid added sugars and refined grains) and 3 key differences (incorporate vs avoid legumes, fruits, and whole intact grains), for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM.Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥ 18 years with prediabetes or T2DM followed a Well Formulated Ketogenic Diet (WFKD) and Mediterranean-Plus diet (Med-Plus) for 12-weeks each, in random order. Diets shared 3 key similarities noted above. Med-Plus incorporated legumes, fruits, and whole intact grains while WFKD avoided them. Primary outcome was % change in HbA1c after 12-weeks on each diet. Secondary and exploratory outcomes included % change in body weight, fasting insulin, glucose, and blood lipids, glucose (continuous glucose monitor), and nutrient intake.Primary analysis had n = 33 with complete data. HbA1c did not differ between diets at 12-weeks. Triglycerides decreased more for WFKD (% change(SEM)): -16%(4%) vs -5%(6%), p = 0.02) and LDL-C was higher for WFKD (+10%(4%) vs -5%(5%), p = 0.01). Weight decreased 8%(1%) vs 7%(1%) and HDL-C increased 11%(2%) vs 7%(3%) for WFKD vs Med-Plus, respectively; however, there was a significant interaction of diet by order for both. Participants had lower intakes of fiber and 3 nutrients on WFKD vs Med-Plus. Twelve-week follow-up data suggested Med-Plus diet was more sustainable.HbA1c was not different between diet phases after 12-weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. WFKD was beneficial for greater decrease in triglycerides, but also had potential untoward risks from elevated LDL-C, and lower nutrient intakes from avoiding legumes, fruits, and whole intact grains, as well as being less sustainable.clinicaltrials.gov NCT03810378.

    View details for DOI 10.1093/ajcn/nqac154

    View details for PubMedID 35641199

  • Adherence to Ketogenic and Mediterranean Study Diets in a Crossover Trial: The Keto-Med Randomized Trial. Nutrients Landry, M. J., Crimarco, A. n., Perelman, D. n., Durand, L. R., Petlura, C. n., Aronica, L. n., Robinson, J. L., Kim, S. H., Gardner, C. D. 2021; 13 (3)

    Abstract

    Adherence is a critical factor to consider when interpreting study results from randomized clinical trials (RCTs) comparing one diet to another, but it is frequently not reported by researchers. The purpose of this secondary analysis of the Keto-Med randomized trial was to provide a detailed examination and comparison of the adherence to the two study diets (Well Formulated Ketogenic Diet (WFKD) and Mediterranean Plus (Med-Plus)) under the two conditions: all food being provided (delivered) and all food being obtained by individual participants (self-provided). Diet was assessed at six time points including baseline (×1), week 4 of each phase when participants were receiving food deliveries (×2), week 12 of each phase when participants were preparing and providing food on their own (×2), and 12 weeks after participants completed both diet phases and were free to choose their own diet pattern (×1). The adherence scores for WFKD and Med-Plus were developed specifically for this study. Average adherence to the two diet patterns was very similar during both on-study time points of the intervention. Throughout the study, a wide range of adherence was observed among participants-for both diet types and during both the delivery phase and self-provided phase. Insight from this assessment of adherence may aid other researchers when answering the important question of how to improve behavioral adherence during dietary trials. This study is registered at clinicaltrials.gov NCT03810378.

    View details for DOI 10.3390/nu13030967

    View details for PubMedID 33802709

  • Gut-microbiota-targeted diets modulate human immune status. Cell Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., Sonnenburg, J. L. 2021

    Abstract

    Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

    View details for DOI 10.1016/j.cell.2021.06.019

    View details for PubMedID 34256014

  • Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight. The American journal of clinical nutrition Fragiadakis, G. K., Wastyk, H. C., Robinson, J. L., Sonnenburg, E. D., Sonnenburg, J. L., Gardner, C. D. 2020

    Abstract

    BACKGROUND: With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood.OBJECTIVES: Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota.METHODS: We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet.RESULTS: While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study.CONCLUSIONS: These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.

    View details for DOI 10.1093/ajcn/nqaa046

    View details for PubMedID 32186326

  • Objective versus Self-Reported Energy Intake Changes During Low-Carbohydrate and Low-Fat Diets OBESITY Guo, J., Robinson, J. L., Gardner, C. D., Hall, K. D. 2019; 27 (3): 420–26

    View details for DOI 10.1002/oby.22389

    View details for Web of Science ID 000459626000010

  • Objective versus Self-Reported Energy Intake Changes During Low-Carbohydrate and Low-Fat Diets. Obesity (Silver Spring, Md.) Guo, J., Robinson, J. L., Gardner, C. D., Hall, K. D. 2019

    Abstract

    OBJECTIVE: This study aimed to compare self-reported with objective measurements of energy intake changes (∆EI) during a 1-year weight-loss intervention with subjects randomized to low-carbohydrate versus low-fat diets.METHODS: Repeated body weight measurements were used as inputs to an objective mathematical model to calculate ∆EIModel and to compare with self-reported energy intake changes assessed by repeated 24-hour recalls (∆EIRecall ).RESULTS: ∆EIRecall indicated a relatively persistent state of calorie restriction of ~500 to 600kcal/d at 3, 6, and 12months with no significant differences between the diets. ∆EIModel demonstrated large early decreases in calorie intake > 800kcal/d followed by an exponential return to ~100kcal/d below baseline at the end of the year. Accounting for self-reported physical activities did not materially affect the results. Discrepancies between ∆EIModel and ∆EIRecall became progressively greater over time. The low-carbohydrate diet resulted in ∆EIModel that was 162±53kcal/d lower than the low-fat diet over the first 3months (P=0.002), but no significant diet differences were found thereafter.CONCLUSIONS: Self-reported ∆EI measurements were inaccurate. Model-based calculations of ∆EI found that instructions to follow the low-carbohydrate diet resulted in greater calorie restriction than the low-fat diet in the early phases of the intervention, but these diet differences were not sustained.

    View details for PubMedID 30672127

  • DIETFITS study (diet intervention examining the factors interacting with treatment success) - Study design and methods. Contemporary clinical trials Stanton, M. V., Robinson, J. L., Kirkpatrick, S. M., Farzinkhou, S., Avery, E. C., Rigdon, J., Offringa, L. C., Trepanowski, J. F., Hauser, M. E., Hartle, J. C., Cherin, R. J., King, A. C., Ioannidis, J. P., Desai, M., Gardner, C. D. 2017; 53: 151-161

    Abstract

    Numerous studies have attempted to identify successful dietary strategies for weight loss, and many have focused on Low-Fat vs. Low-Carbohydrate comparisons. Despite relatively small between-group differences in weight loss found in most previous studies, researchers have consistently observed relatively large between-subject differences in weight loss within any given diet group (e.g., ~25kg weight loss to ~5kg weight gain). The primary objective of this study was to identify predisposing individual factors at baseline that help explain differential weight loss achieved by individuals assigned to the same diet, particularly a pre-determined multi-locus genotype pattern and insulin resistance status. Secondary objectives included discovery strategies for further identifying potential genetic risk scores. Exploratory objectives included investigation of an extensive set of physiological, psychosocial, dietary, and behavioral variables as moderating and/or mediating variables and/or secondary outcomes. The target population was generally healthy, free-living adults with BMI 28-40kg/m(2) (n=600). The intervention consisted of a 12-month protocol of 22 one-hour evening instructional sessions led by registered dietitians, with ~15-20 participants/class. Key objectives of dietary instruction included focusing on maximizing the dietary quality of both Low-Fat and Low-Carbohydrate diets (i.e., Healthy Low-Fat vs. Healthy Low-Carbohydrate), and maximally differentiating the two diets from one another. Rather than seeking to determine if one dietary approach was better than the other for the general population, this study sought to examine whether greater overall weight loss success could be achieved by matching different people to different diets. Here we present the design and methods of the study.

    View details for DOI 10.1016/j.cct.2016.12.021

    View details for PubMedID 28027950