Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: the Interventional Keto-Med Randomized Crossover Trial.

May combine two claims.

Weight decreased 8% (SEM, 1%) on the WFKD and 7% (SEM, 1%) on the Med-Plus.

“Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%)”

• AssumptionRests on an assumption: There was no carryover effect between the two diet phases despite the absence of a washout period.

May combine two claims.

HDL cholesterol increased 11% (SEM, 2%) on the WFKD and 7% (SEM, 3%) on the Med-Plus.

“HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively”

• AssumptionRests on an assumption: There was no carryover effect between the two diet phases despite the absence of a washout period.

Probably not a substantial claim: may not pass S3 (load-bearing).

Within diets, variability was highest when participants were on the WFKD and self-providing foods.

“Within diets, variability was highest when participants were on the WFKD and self-providing foods.”

• AssumptionRests on an assumption: There was no carryover effect between the two diet phases despite the absence of a washout period.

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus.

“Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus.”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the Med-Plus decreased nutrient intakes of vitamin B12 and calcium compared to baseline during the food-delivery period.

“On average, participants on the Med-Plus increased their nutrient intakes of folate, omega-3 fats, and vitamins C and E and decreased their nutrient intakes of vitamin B12 and calcium compared to baseline.”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the WFKD increased nutrient intakes of vitamins B12, C, and E and omega-3 fats compared to baseline during the food-delivery period.

“On average, participants on the WFKD increased their nutrient intakes of vitamins B12, C, and E and omega-3 fats and decreased their nutrient intakes of thiamin, folate, and calcium compared to baseline (see Supplemental Table 9).”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the WFKD decreased nutrient intakes of thiamin, folate, and calcium compared to baseline during the food-delivery period.

“On average, participants on the WFKD increased their nutrient intakes of vitamins B12, C, and E and omega-3 fats and decreased their nutrient intakes of thiamin, folate, and calcium compared to baseline (see Supplemental Table 9).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

On average, participants on the Med-Plus increased nutrient intakes of folate, omega-3 fats, and vitamins C and E compared to baseline during the food-delivery period.

“On average, participants on the Med-Plus increased their nutrient intakes of folate, omega-3 fats, and vitamins C and E and decreased their nutrient intakes of vitamin B12 and calcium compared to baseline.”

Probably not a substantial claim: may not pass S3 (load-bearing).

During the 4-week food-delivery period, when adherence was highest, the WFKD had higher intake changes from baseline than Med-Plus for vitamins B12 and D and selenium.

“When contrasting changes in nutrient intakes from baseline between the 2 diets at the end of the 4-week food-delivery periods, when adherence was highest, intake was higher (ASD >0.5) for the WKFD for 3 nutrients (vitamins B12 and D and selenium) and higher for the Med-Plus for fiber and 7 nutrients (thiamin, iron, folate, magnesium, and vitamins B6, C, and E; see Supplemental Table 8).”

May combine two claims.

For participants with prediabetes, both diets increased time in range (70-140 mg/dL), with a greater increase for the WFKD.

“Both diets increased the TIR (70–140 mg/dL for prediabetes), with a greater increase for the WFKD.”

May combine two claims.

For participants with T2DM, both diets decreased average glucose levels and increased time in range (70-180 mg/dL), with the WFKD having a greater absolute effect.

“For the participants with T2DM, both diets decreased average glucose levels and increased TIR (70–180 mg/dL for T2DM), with the WFKD having a greater absolute effect (Supplemental Figure 4; Supplemental Table 16).”

May combine two claims.

Twelve weeks after completing both diet phases, relative to baseline, on average, participants maintained decreased HbA1c values, fasting glucose levels, and weight.

“Twelve weeks after completing both diet phases, relative to baseline, on average, the participants maintained decreased HbA1c values, fasting glucose levels, and weight (CGM data were not collected at follow-up).”

• AssumptionRests on an assumption: Self-reported home weighing is a valid substitute for measured weight during the COVID-19 pandemic.

Probably not a substantial claim: may not pass S3 (load-bearing).

During the trial, two adverse events (kidney infection and exacerbation of eczema) were possibly but probably not related to the study, occurring in participants on the WFKD.

“Two of the 4 adverse events that were possibly but probably not related to the study were a kidney infection and exacerbation of eczema (the participants were on the WFKD during the time of their event).”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the Med-Plus did not increase or decrease intake of any nutrient during the self-provided period compared to baseline.

“On average, participants on the Med-Plus did not increase or decrease intake of any nutrient during the self-provided period compared to baseline.”

May combine two claims.

At follow-up, fasting insulin, triglyceride, and ALT data were similar to baseline.

“Fasting insulin, triglyceride, and ALT data were similar at follow-up compared to baseline.”

May combine two claims.

In a secondary analysis, there was a significant diet × diabetes status interaction for ALT (P = 0.04), with a modestly greater decrease in ALT for participants with prediabetes on Med-Plus and for participants with T2DM on WFKD.

“The only notable finding was a modestly greater decrease in ALT for the participants with prediabetes on the Med-Plus [mean, −0.17 (95% CI: −0.29 to −0.05) compared with −0.04 (95% CI: −0.25 to 0.16) for prediabetes compared with T2DM, respectively] and, alternatively, a modestly greater decrease in ALT for participants with T2DM on the WFKD [mean, −0.1 (95% CI: −0.21 to 0) compared with −0.14 (95”

May combine two claims.

There was a general trend towards improvements for both diet phases for most secondary outcomes, but no significant differences between diets in the primary analysis for fasting glucose, insulin, HDL cholesterol, and ALT.

“There was a general trend towards improvements for both diet phases for most of the secondary outcomes, but no significant differences between diets in the primary analysis for fasting glucose, insulin, HDL cholesterol, and ALT data.”

May combine two claims.

In sensitivity analysis, there was no significant difference in HbA1c values between diets when adjusting for baseline weight and percentage weight change (P = 0.45), nor when adjusting for percentage weight change alone (P = 0.45).

“We did not observe a significant difference in HbA1c values between diets when adjusting for baseline weight and percentage weight change (P = 0.45), nor when adjusting for percentage weight change alone (P = 0.45).”

May combine two claims.

In both participants with prediabetes and T2DM, both diets decreased the coefficient of variation (CV), with the WFKD having a greater effect in both populations.

“Both in participants with prediabetes and participants with T2DM, both diets decreased the CV. Again, the WFKD had a greater effect in both populations.”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the WFKD decreased thiamin, folate, and iron intake compared to baseline during the self-provided period.

“On average, participants on the WFKD increased their nutrient intake of vitamin E and decreased their nutrient intakes of thiamin, folate, and iron compared to baseline (see Supplemental Table 11).”

May combine two claims.

The only time point at which the weight loss difference between arms was significant was at week 12, at the end of the first diet phase, with a mean difference of 6.9 kg (SEM ±0.8) for WFKD compared with 5.0 kg (SEM ±0.80) for Med-Plus (P = 0.04; paired t-test).

“The only time point at which the weight loss difference was significant was at week 12, at the end of the first diet phase, with a mean difference of 6.9 kg (SEM, ±0.8 kg) compared with 5.0 kg (SEM, ±0.80 kg) for the WFKD and Med-Plus, respectively (P = 0.04; paired t-test).”

• Also stated in: § Primary and secondary analyses · plain

  “Here, we observe a difference between arms at week 12 after phase 1 but not phase 2.”

• AssumptionRests on an assumption: Self-reported home weighing is a valid substitute for measured weight during the COVID-19 pandemic.

Probably not a substantial claim: may not pass S3 (load-bearing).

During the trial, one elevated ALT level was likely related to the study, occurring in a participant on the WFKD.

“One was an elevated ALT level likely related to the study (the participant was on the WFKD during the time of the event).”

Probably not a substantial claim: may not pass S3 (load-bearing).

On average, participants on the WFKD increased vitamin E intake compared to baseline during the self-provided period.

“On average, participants on the WFKD increased their nutrient intake of vitamin E and decreased their nutrient intakes of thiamin, folate, and iron compared to baseline (see Supplemental Table 11).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

During the trial, one transient ischemic attack occurred during study follow-up and was probably not related to the study, in a participant on the Med-Plus.

“The fourth was a transient ischemic attack that occurred during the study follow-up, and was probably not related to the study (the participant was on the Med-Plus during the time of the event).”

May combine two claims.

Although the WFKD was associated with improved glucose control on several CGM metrics, the differences in HbA1c values were modest despite 50% lower carbohydrate intake on the WFKD compared with the Med-Plus (<20% compared with <40% of total calories from carbohydrates, respectively).

“Although the WFKD was associated with improved glucose control on several CGM metrics, the differences in HbA1c values were modest despite 50% lower carbohydrate intake on the WFKD compared with the Med-Plus (<20% compared with <40% of total calories from carbohydrates, respectively).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The trial was registered at clinicaltrials.gov as NCT03810378.

“This trial was registered at clinicaltrials.gov as NCT03810378.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All study participants provided written informed consent.

“All study participants provided written informed consent.”

Classified as probably not a substantial claim. May combine two claims.

The study used a 2-sided likelihood ratio test and a linear mixed model to evaluate differences between diets while adjusting for fixed effects of order and diabetes status and a random effect for participant.

“We used a 2-sided likelihood ratio test and a linear mixed model to evaluate the differences between diets (the WFKD compared with the Med-Plus) while adjusting for the fixed effects of order (e.g., study arm) and prediabetes compared with T2DM status and for a random effect to account for the correlated observations of each participant.”

Probably not a substantial claim: may not pass S4 (based).

The improvement in HbA1c from baseline on both diets was likely due to several shared dietary aspects.

“likely due to several shared dietary aspects”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study investigated an interaction term for a differential effect of diet × order from the crossover design to assess interpretability of the main effect for diet.

“Additionally, we investigated an interaction term for a differential effect of diet × order from the crossover design to assess interpretability of the main effect for diet.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Diet randomization used an allocation sequence determined by computerized random-number generation in block sizes of 4 by a statistician not involved in intervention delivery or data collection.

“Diet randomization was performed using an allocation sequence determined by computerized, random-number generation in block sizes of 4 by a statistician not involved in the intervention delivery or data collection.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study carried out a sensitivity analysis to exclude participants who took different dosages of sulfonylurea medication between diets.

“Because sulfonylurea medications are known to alter HbA1c values, we carried out a sensitivity analysis to exclude participants who took different dosages of this class of medication between diets.”

• AssumptionRests on an assumption: Sulfonylurea medications alter HbA1c values.

Probably not a substantial claim: may not pass S3 (load-bearing).

The sample size was determined by resource availability.

“The sample size was determined by resource availability.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Randomization was stratified by prediabetes compared with T2DM status.

“Randomization was stratified by prediabetes compared with T2DM status.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

No correction was applied for multiple comparisons, and secondary and exploratory analyses should be interpreted accordingly.

“No correction was applied for multiple comparisons, and secondary and exploratory analyses should be interpreted accordingly.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In a prespecified sensitivity analysis of the primary outcome, the study adjusted for baseline weight and percentage weight change from baseline.

“Therefore, in a prespecified sensitivity analysis of the primary outcome, we adjusted for the baseline weight and percentage weight change from baseline.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study procedures were approved by the Stanford University Human Subjects Committee (institutional review board protocol 49218).

“Procedures for this study were followed in accordance with the ethical standards from the Helsinki Declaration and were approved by the Stanford University Human Subjects Committee (institutional review board protocol 49218).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants did not learn of their diet sequence until they had completed all baseline laboratory measures and surveys.

“Participants did not learn of their diet sequence until they had completed all baseline laboratory measures and surveys.”

Probably not a substantial claim: may not pass S3 (load-bearing).

There was no parallel biochemical parameter for Med-Plus adherence.

“There was no parallel biochemical parameter for Med-Plus adherence.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Blood pressure data were the most severely impacted by COVID-19, and no blood pressure results are presented due to a high proportion of missing data.

“Of all study variables, blood pressure data were the most severely impacted by COVID-19; no blood pressure results are presented due to a high proportion of missing data.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The primary analysis was of 33 participants with complete data.

“The primary analysis was of 33 participants with complete data.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants whose end-of-phase blood draws were scheduled during the initial shelter-in-place order were asked to extend the duration of their assigned diets until in-person blood draw visits restarted.

“participants whose end-of-phase blood draws were scheduled during the initial shelter-in-place order were asked to extend the duration of their assigned diets until research staff were able to restart in-person blood draw visits in early June 2020.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In a sensitivity analysis for the potential impact of COVID-19, the study compared the 2 diets in the first phase only.

“In a sensitivity analysis for the potential impact of the COVID-19 pandemic, we compared the 2 diets in the first phase only.”

Classified as probably not a substantial claim.

Participants who did not complete both phases were excluded from the primary analysis, as prespecified in the statistical analysis plan.

“As prespecified in the statistical analysis plan, participants who did not complete both phases (i.e., crossover) were excluded.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study used validated questionnaires about quality of life, perceived cognitive function, wellness, and gastrointestinal symptoms.

“Participants completed validated questionnaires about their quality of life, perceived cognitive function, wellness, and gastrointestinal symptoms, including stool types, at baseline, during weeks 4 and 12 of each diet phase, and at follow-up (27–30).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data collection designed to be remote continued without disruption during shelter-in-place, including online surveys, dietary recalls, CGMs, and stool kits.

“All data collection that was designed from the onset to be collected remotely continued without disruption during the shelter-in-place, with data collected according to the original timeline; this included online surveys, dietary recalls (via phone call), CGMs, and stool kits (mailed directly to participants).”

Classified as probably not a substantial claim.

Individuals with prediabetes and those with T2DM have different glucose target ranges.

“Individuals with prediabetes were analyzed separately from those with T2DM, because these groups have different glucose target ranges (31).”

• cites [31] Battelino, 2019, Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diabetes UK emphasized considering food patterns over macronutrient composition and gave the highest rating for the Mediterranean diet for patients with and at risk for T2DM.

“Diabetes UK also emphasized considering food patterns over macronutrient composition and gave the highest rating for the Mediterranean diet for patients with and at risk for T2DM.”

• cites [1] Dyson, 2018, Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes, Diabetes Med. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The American Diabetes Association did not recommend a specific, single dietary pattern, but recommended several, including the Mediterranean diet and low-carbohydrate and very low-carb diets.

“In contrast, the ADA did not recommend a specific, single dietary pattern, but recommended several, including the Mediterranean diet and low-carbohydrate (low-carb) and very low-carb diets.”

• cites [2] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diabetes UK and the American Diabetes Association endorsed an individualized approach and agreed on incorporating nonstarchy vegetables and minimizing added sugars and refined grains.

“endorsing an individualized approach and agreeing on several key nutrition recommendations, including: 1) incorporating nonstarchy vegetables; and 2) minimizing added sugars and refined grains.”

• cites [1] Dyson, 2018, Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes, Diabetes Med. sourceNot checked yet

  Not checked in the free run.

• cites [2] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Legumes, fruits, and whole, intact grains are consistently recommended by national and international public health organizations based on extensive evidence of cardiovascular benefits of fiber, antioxidants, and the vitamins and minerals characteristic of those food groups.

“These 3 food groups are consistently recommended by national and international public health organizations based on extensive evidence of cardiovascular benefits of fiber, antioxidants, and the vitamins and minerals characteristic of those food groups (2, 12–15).”

• cites [2] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

• cites [12] 2020Not checked yet

  Not checked in the free run.

• cites [13] Arnett, 2019, 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol. sourceNot checked yet

  Not checked in the free run.

• cites [14] Rock, 2020, American Cancer Society guideline for diet and physical activity for cancer prevention, CA Cancer J Clin. sourceNot checked yet

  Not checked in the free run.

• cites [15] Nishida, 2004, The joint WHO/FAO expert consultation on diet, nutrition and the prevention of chronic diseases: process, product and policy implications, Public Health Nutr. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

A glucose management indicator was not calculated because 14 days of data are generally recommended for this metric and only 10 days were available.

“A glucose management indicator was not calculated, as 14 days of data are generally recommended for this metric and only 10 days were available.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Average glucose and time-in-range are considered the most important CGM metrics for clinical decision-making, and CV is the standard metric for glucose variability.

“Average glucose and time-in-range (TIR) values are considered the most important CGM metrics for clinical decision-making, and CV is the standard metric for glucose variability (31); these 3 factors are presented as exploratory outcomes.”

• cites [31] Battelino, 2019, Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In 2018-2019, both Diabetes UK and the American Diabetes Association released nutrition guidelines for preventing and managing diabetes.

“In 2018–2019, both Diabetes UK and the American Diabetes Association (ADA) released nutrition guidelines for preventing and managing diabetes (1, 2)”

• cites [1] Dyson, 2018, Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes, Diabetes Med. sourceNot checked yet

  Not checked in the free run.

• cites [2] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The American Diabetes Association suggested reducing overall carbohydrate intake to decrease blood glucose levels and noted that in select adults with T2DM, low- or very low-carb eating patterns were viable approaches.

“In addition, for the first time, the ADA suggested reducing overall carbohydrate intake to decrease blood glucose levels and noted that in select adults with T2DM, low- or very low-carb eating patterns were viable approaches.”

• cites [2] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The food-delivery company being a dairy-free (and gluten-free) operation likely explained the decreases in calcium for both diet phases.

“The food-delivery company is a dairy-free (and gluten-free) operation, and this likely explained the decreases in calcium for both diet phases.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants were not blinded to their blood glucose readings.

“Participants were not blinded to these blood glucose readings.”

May combine two claims.

Sensitivity analyses had low power due to the small sample size, and their results should be interpreted with caution.

“However, these analyses had low power due to the small sample size, and their results should be interpreted with caution.”

May combine two claims.

At 12-weeks follow-up, participants' dietary patterns were more similar to the Med-Plus, suggesting a potential for greater sustainability of the Med-Plus in the long term.

“At the 12-weeks follow-up, the participants’ dietary patterns were more similar to the Med-Plus, suggesting a potential for greater sustainability of the Med-Plus in the long term.”

May combine two claims.

Our findings corroborate previous evidence indicating that HbA1c levels can be significantly reduced on both a ketogenic diet and a Mediterranean diet, especially if the diet is restricted in added sugars and refined carbohydrates.

“Our findings corroborate previous evidence indicating that HbA1c levels can be significantly reduced on both a ketogenic diet (35–38) and a Mediterranean diet (39–44), especially if the diet is restricted in added sugars and refined carbohydrates (2).”

• cites [35] Kirkpatrick, 2019, J Clin Lipidol. sourceNot checked yet

  Not checked in the free run.

• cites [36] Hall, 2021, Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake, Nat Med. sourceNot checked yet

  Not checked in the free run.

• cites [37] Yuan, 2020, Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis, Nutr Diabetes. sourceNot checked yet

  Not checked in the free run.

• cites [38] Athinarayanan, 2019, Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: a 2-year non-randomized clinical trial, Front Endocrinol. sourceNot checked yet

  Not checked in the free run.

• cites [39] Sleiman, 2015, Effect of Mediterranean diet in diabetes control and cardiovascular risk modification: a systematic review, Front Public Health. sourceNot checked yet

  Not checked in the free run.

• cites [40] Esposito, 2015, A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses, BMJ Open. sourceNot checked yet

  Not checked in the free run.

• cites [41] Esposito, 2009, Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial, Ann Intern Med. sourceNot checked yet

  Not checked in the free run.

• cites [42] Maiorino, 2017, Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: follow-up of a randomized trial, Eur J Prev Cardiol. sourceNot checked yet

  Not checked in the free run.

• cites [43] Itsiopoulos, 2011, Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a randomized cross-over study, Nutr Metab Cardiovasc Dis. sourceNot checked yet

  Not checked in the free run.

• cites [44] Toobert, 2003, Biologic and quality-of-life outcomes from the Mediterranean lifestyle program: a randomized clinical trial, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The initial 4-week period of food delivery facilitated high adherence, while the latter 8 weeks of self-provided foods in the 12-week diet phases increased generalizability.

“Second, the initial 4-week period of food delivery facilitated high adherence, while the latter 8 weeks of self-provided foods in the 12-week diet phases increased generalizability.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

During the pandemic, weight or blood pressure data were not able to be measured; self-reported home weighing was accepted for weight, and blood pressure data are not presented.

“In addition, during the pandemic, while we were able to manage blood collections through an alternative site, weight or blood pressure data were not able to be measured. To continue collecting participants’ weight data, we accepted self-reported home weighing from those participants. We were not able to find an alternate approach to measure blood pressure; thus, blood pressure data are not”

• AssumptionRests on an assumption: Self-reported home weighing is a valid substitute for measured weight during the COVID-19 pandemic.

May combine two claims.

The relatively small sample size was a limitation, although the crossover design was helpful in maximizing the control of many potentially confounding variables.

“A second limitation was the relatively small sample size, although the crossover design was helpful in maximizing the control of many potentially confounding variables.”

May combine two claims.

Increases in LDL cholesterol and decreases in triglycerides are common effects of low-carb diets, and have been linked with a shift in the LDL cholesterol particle size that is associated with a decreased cardiovascular risk.

“Increases in LDL cholesterol and decreases in triglycerides are common effects of low-carb diets, and have been linked with a shift in the LDL cholesterol particle size that is associated with a decreased cardiovascular risk (45–48).”

• cites [45] Sharman, 2002, A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men, J Nutr. sourceNot checked yet

  Not checked in the free run.

• cites [46] Krauss, 2006, Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia, Am J Clin Nutr. sourceNot checked yet

  Not checked in the free run.

• cites [47] Sharman, 2004, Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men, J Nutr. sourceNot checked yet

  Not checked in the free run.

• cites [48] Bhanpuri, 2018, Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study, Cardiovasc Diabetol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Through the production of beta-hydroxybutyrate, the WFKD has been suggested to reduce some of the requirement for butyrate, which is likely responsible for some of the benefits of dietary fiber.

“However, through the production of beta-hydroxybutyrate, the WFKD has been suggested to reduce some of the requirement for butyrate, which is likely responsible for some of the of the benefits of dietary fiber (49).”

• cites [49] Wood, 2007, Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk, Metabolism. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Both the WFKD and Med-Plus were associated with improved blood glucose and reduced body weight, both of which occurred without guidance on caloric restriction and may relate to the similarities in the 2 diet patterns, which limited added sugars and refined sugars.

“We found that both the WFKD and Med-Plus were associated with improved blood glucose and reduced body weight, both of which occurred without guidance on caloric restriction and may relate to the similarities in the 2 diet patterns, which limited added sugars and refined sugars.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The 12-week follow-up after completion of the 2 intervention phases provided insights regarding the poststudy stability of diet behaviors.

“Third, the 12-week follow-up after completion of the 2 intervention phases provided insights regarding the poststudy stability of diet behaviors.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study chose a well-established clinical value as the primary outcome: HbA1c.

“Fourth, we chose a well-established clinical value as the primary outcome: HbA1c.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Concerns about the pandemic and extended delays led to 4 participants dropping out who might have otherwise completed the study.

“Unfortunately, concerns about the pandemic and the extended delays led to 4 participants dropping out who might have otherwise completed the study.”

May combine two claims.

Our study suggests it was difficult for participants to maintain the WFKD, as well as to achieve and maintain the similarities in the 2 diets in terms of restricting added sugars and refined grains.

“Finally, regardless of benefits, diets need to be sustainable, and our study suggests it was difficult for participants to maintain the WFKD, as well as to achieve and maintain the similarities in the 2 diets in terms of restricting added sugars and refined grains.”

Classified as probably not a substantial claim. May combine two claims.

The rise in LDL cholesterol, decrease in fiber intake, and greater potential for nutrient deficiencies on the WFKD may be concerning; longer-term studies will be needed to understand these associations with clinical outcomes.

“In addition, the rise in LDL cholesterol, decrease in fiber intake, and greater potential for nutrient deficiencies on the WFKD may be concerning; longer-term studies will be needed to understand these associations with clinical outcomes.”

Classified as probably not a substantial claim.

The crossover design allowed participants to serve as their own controls.

“First, the crossover design allowed participants to serve as their own controls.”

• AssumptionThe authors state this as an assumption: The 12-week diet phase durations were sufficient to eliminate or minimize any carryover effects.

Probably not a substantial claim: may not pass S3 (load-bearing).

The study assessed an extensive set of well-studied secondary clinical outcomes to evaluate overall cardiometabolic health.

“Fifth, we assessed an extensive set of well-studied secondary clinical outcomes to evaluate overall cardiometabolic health.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The conduct of the study was disrupted in several ways by COVID-19.

“First, the conduct of the study was disrupted in several ways by COVID-19.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Adherence among participants who did not receive food delivery was similarly high compared to adherence among those who did receive food delivery during that study phase.

“Fortunately, adherence among those participants was determined to be similarly high compared to adherence among those who did receive food delivery during that study phase.”

Probably not a substantial claim: may not pass S3 (load-bearing).

An important design strength was emphasizing high-quality dietary choices for both diet phases.

“Finally, we believe an important design strength was emphasizing high-quality dietary choices for both diet phases (50), as exemplified by using the WFKD for the ketogenic diet phase and by an emphasis on avoiding refined grains and added sugars for the Mediterranean diet phase.”

• cites [50] Gardner, 2020, Nutrition study design issues—important issues for interpretation, Am J Health Promot. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Twelve of the participants did not receive delivered food for the first 4 weeks of their second phase of the crossover.

“Also, the pandemic was a problem for the collaborating partner that provided food to study participants, and 12 of the participants did not receive delivered food for the first 4 weeks of their second phase of the crossover.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Including and collecting CGM data proved valuable, particularly because the COVID-19 shelter-in-place disruption did not impact home collection of CGM data as much as it did HbA1c data obtained from blood samples drawn in research clinics.

“Sixth, it proved valuable to include and collect CGM data, particularly because the COVID-19 shelter-in-place disruption did not impact home collection of CGM data as much as it did HbA1c data obtained from blood samples drawn in research clinics.”

May combine two claims.

Extensive diet data collection using state-of-the-art NDS-R allowed the study to assess adherence and compare nutrient intakes.

“Seventh, extensive diet data collection using state-of-the-art NDS-R allowed us to assess adherence—an important metric in free-living trials (50)—and to compare nutrient intakes.”

• cites [50] Gardner, 2020, Nutrition study design issues—important issues for interpretation, Am J Health Promot. sourceNot checked yet

  Not checked in the free run.