Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial

Front Endocrinol (Lausanne). 2023 Nov 14:14:1243910. doi: 10.3389/fendo.2023.1243910. eCollection 2023.

Abstract

Background: Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health.

Methods: We randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months.

Results: Participants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m2, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p<0.05 vs. baseline), as opposed to HDG dieters (+4%[-12 nmol/L], p=0.28 vs. baseline), whereas Green-MED diet FMC change was significant as compared to HDG diet group (p=0.048 multivariable models). Overall, 18-month decrease in FMC levels was associated with favorable changes in FPG, HbA1c, hsCRP, TSH, testosterone and MRI-assessed hepatosteatosis, and with unfavorable changes of HDLc (p<0.05 for all, weight loss adjusted, multivariable models).

Conclusion: Long-term adherence to MED diets, and mainly green-MED/high polyphenols diet, may lower FMC, stress hormone, levels,. Lifestyle-induced FMC decrease may have potential benefits related to cardiometabolic health, irrespective of weight loss.

Clinical trial registration: ClinicalTrials.gov, identifier NCT03020186.

Keywords: cardiometabolic health; fasting plasma cortisol; insulin resistance; lifestyle intervention; mediterranean diet; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein
  • Cardiovascular Diseases*
  • Diabetes Mellitus, Type 2*
  • Diet, Mediterranean*
  • Fasting
  • Female
  • Glycated Hemoglobin
  • Humans
  • Hydrocortisone
  • Male
  • Middle Aged
  • Testosterone
  • Thyrotropin
  • Weight Loss / physiology

Substances

  • C-Reactive Protein
  • Glycated Hemoglobin
  • Hydrocortisone
  • Testosterone
  • Thyrotropin

Associated data

  • ClinicalTrials.gov/NCT03020186

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project number 209933838 – Collaborative Research Center SFB1052 “Obesity Mechanisms”, to IS (SFB-1052/B11); the Israel Ministry of Health (grant no. 87472511), Ministry of Science and Technology, Israel (grant 3-13604); and the California Walnuts Commission. None of the foundations was involved in any stage of the design, conduct, or analysis of the study and had no access to the study results before publication.