Anja Kroke

Purpose: This umbrella review aimed to investigate the evidence for an association of dietary intake of total protein as well as animal and plant protein with the incidence of coronary heart disease (CHD), stroke and total cardiovascular diseases (CVD). Methods: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis (MA) published between January 2012 and April 2024. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence were assessed using established tools and predefined criteria. Results: Ten SRs were considered eligible for the umbrella review; all were based on prospective cohort studies, and six conducted a MA. Dietary intakes of total, animal and plant protein were not associated with the risk of CHD or stroke. For CHD, the overall certainty of evidence for the absence of an association was “probable” for total, animal and plant protein. For stroke and total CVD, the overall certainty of evidence was rated as “possible” for the absence of an association with the intake of total protein and plant protein and insufficient for animal protein intake. Conclusion: Given that most SRs on dietary protein intake did not indicate an association, it seems that protein intake plays no major role in the development of CVD. This investigation was registered at PROSPERO as CRD42018082395.

Introduction: This umbrella review aimed to investigate the evidence of an effect of dietary intake of total protein, animal and plant protein on blood pressure (BP), and hypertension (PROSPERO: CRD42018082395). Methods: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis published between 05/2007 and 10/2022. The methodological quality and outcome-specific certainty of evidence were assessed by the AMSTAR 2 and NutriGrade tools, followed by an assessment of the overall certainty of evidence. SRs investigating specific protein sources are described in this review, but not included in the assessment of the overall certainty of evidence. Results: Sixteen SRs were considered eligible for the umbrella review. Ten of the SRs investigated total protein intake, six animal protein, six plant protein and four animal vs. plant protein. The majority of the SRs reported no associations or effects of total, animal and plant protein on BP (all “possible” evidence), whereby the uncertainty regarding the effects on BP was particularly high for plant protein. Two SRs addressing milk-derived protein showed a reduction in BP; in contrast, SRs investigating soy protein found no effect on BP. The outcome-specific certainty of evidence of the SRs was mostly rated as low. Discussion/conclusion: This umbrella review showed uncertainties whether there are any effects on BP from the intake of total protein, or animal or plant proteins, specifically. Based on data from two SRs with milk protein, it cannot be excluded that certain types of protein could favourably influence BP.

Purpose: This umbrella review aimed to assess whether dietary protein intake with regard to quantitative (higher vs. lower dietary protein intake) and qualitative considerations (total, plant-based or animal-based protein intake) affects body weight (BW), fat mass (FM) and waist circumference (WC). Methods: A systematic literature search was conducted in PubMed, Embase and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with and without meta-analyses of prospective studies published between 04 October 2007 and 04 January 2022. Methodological quality and outcome-specific certainty of evidence of the retrieved SRs were assessed by using AMSTAR 2 and NutriGrade, respectively, in order to rate the overall certainty of evidence using predefined criteria. Results: Thirty-three SRs were included in this umbrella review; 29 were based on randomised controlled trials, a few included cohort studies. In studies without energy restriction, a high-protein diet did not modulate BW, FM and WC in adults in general (all “possible” evidence); for older adults, overall certainty of evidence was “insufficient” for all parameters. Under hypoenergetic diets, a high-protein diet mostly decreased BW and FM, but evidence was “insufficient” due to low methodological quality. Evidence regarding an influence of the protein type on BW, FM and WC was “insufficient”. Conclusion: “Possible” evidence exists that the amount of protein does not affect BW, FM and WC in adults under isoenergetic conditions. Its impact on the reduction in BW and FM under hypoenergetic conditions remains unclear; evidence for an influence of protein type on BW, FM and WC is “insufficient”.

Purpose: Protein-rich foods show heterogeneous associations with the risk of type 2 diabetes (T2D) and it remains unclear whether habitual protein intake is related to T2D risk. We carried out an umbrella review of systematic reviews (SR) of randomised trials and/or cohort studies on protein intake in relation to risks of T2D. Methods: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and T2D risk published between July 1st 2009 and May 22nd 2022, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. Results: Eight SRs were identified of which six contained meta-analyses. The majority of SRs on total protein intake had moderate or high methodological quality and moderate outcome-specific certainty of evidence according to NutriGrade, however, the latter was low for the majority of SRs on animal and plant protein. Six of the eight SRs reported risk increases with both total and animal protein. According to one SR, total protein intake in studies was ~ 21 energy percentage (%E) in the highest intake category and 15%E in the lowest intake category. Relative Risks comparing high versus low intake in most recent SRs ranged from 1.09 (two SRs, 95% CIs 1.02–1.15 and 1.06–1.13) to 1.11 (1.05–1.16) for total protein (between 8 and 12 cohort studies included) and from 1.13 (1.08–1.19) to 1.19 (two SRs, 1.11–1.28 and 1.11–1.28) (8–9 cohort studies) for animal protein. However, SRs on RCTs examining major glycaemic traits (HbA_1c, fasting glucose, fasting insulin) do not support a clear biological link with T2D risk. For plant protein, some recent SRs pointed towards risk decreases and non-linear associations, however, the majority did not support an association with T2D risk. Conclusion: Higher total protein intake was possibly associated with higher T2D risk, while there is insufficient evidence for a risk increase with higher intakes of animal protein and a risk decrease with plant protein intake. Given that most SRs on plant protein did not indicate an association, there is possibly a lack of an effect.

Purpose: Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted. Methods: PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria. Results: Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as ‘possible’ for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as ‘probable’ or ‘possible’ for most other kidney function-related parameters to be physiologically increased with HPI. Conclusion: Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.

This umbrella review aimed at assessing whether a protein intake exceeding the current recommendation for younger (0.8 g/kg body weight [BW]/day) and older (1.0 g/kg BW/day) adults affects bone mineral density and fracture risk. Moreover, the effect of animal or plant protein was evaluated. A systematic literature search was conducted in PubMed, Embase, and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with or without meta-analysis of prospective studies published between 11/2008 and 08/2021. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence of the retrieved SRs were assessed using established tools and predefined criteria. Eleven SRs of randomized controlled trials (RCTs) and/or cohort studies were included. In SRs of cohort studies and RCTs, protein intake/kg BW/day ranged between 0.21–0.95 g (low intake) and > 1.24 g (high intake), respectively, and between 0.67–1.1 g (control groups) and 1.01–1.69 g (intervention groups), respectively. The vast majority of outcome-specific certainty of evidence was rated “low” or “very low.” The overall certainty of evidence for an association (cohort studies) or effect (RCTs) of total, animal or plant protein intake on each of the investigated outcomes was rated “insufficient,” with the exception of possible evidence for a reduced hip fracture risk by high vs. low protein intake. Since protein intakes in low/control and high/intervention groups were very heterogeneous and with low certainty of evidence, it remains unclear whether a dose above the current recommendation or type of protein intake (animal or plant protein) affects bone health overall. However, there is possible evidence for reduced hip fracture risk with high versus low protein intake.

Purpose: The present work aimed to delineate (i) a revised protocol according to recent methodological developments in evidence generation, to (ii) describe its interpretation, the assessment of the overall certainty of evidence and to (iii) outline an Evidence to Decision framework for deriving an evidence-based guideline on quantitative and qualitative aspects of dietary protein intake. Methods: A methodological protocol to systematically investigate the association between dietary protein intake and several health outcomes and for deriving dietary protein intake recommendations for the primary prevention of various non-communicable diseases in the general adult population was developed. Results: The developed methodological protocol relies on umbrella reviews including systematic reviews with or without meta-analyses. Systematic literature searches in three databases will be performed for each health-related outcome. The methodological quality of all selected systematic reviews will be evaluated using a modified version of AMSTAR 2, and the outcome-specific certainty of evidence for systematic reviews with or without meta-analysis will be assessed with NutriGrade. The general outline of the Evidence to Decision framework foresees that recommendations in the derived guideline will be given based on the overall certainty of evidence as well as on additional criteria such as sustainability. Conclusion: The methodological protocol permits a systematic evaluation of published systematic reviews on dietary protein intake and its association with selected health-related outcomes. An Evidence to Decision framework will be the basis for the overall conclusions and the resulting recommendations for dietary protein intake.

Emerging evidence suggests that maternal prepregnancy body mass index or weight (MPBW) may be associated with offspring's blood pressure (BP). Therefore, we conducted a systematic review—following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses statement—to assess and judge the evidence for an association between MPBW with offspring's later BP. Five data bases were searched without limits. Risk of bias was assessed using the “Tool to Assess Risk of Bias in Cohort Studies,” and an evidence grade was allocated following the World Cancer Research Fund criteria. Of 2,011 publications retrieved, 16 studies (all cohort studies) were included in the systematic review; thereof, 5 studies (31%) were rated as good‐quality studies. Overall, data from 63,959 participants were enclosed. Systolic BP was analysed in 15 (5 good quality), diastolic BP in 12 (3 good quality), and mean arterial pressure in 3 (no good quality) studies. Five good‐quality studies of MPBW with offspring's systolic BP as the outcome and 1 good‐quality study with offspring's diastolic BP as the outcome observed a significant association. However, after adding offspring's anthropometry variables to the statistical model, the effect attenuated in 4 studies with systolic BP to nonsignificance, the study with diastolic BP remained significant. No good‐quality studies were found with respect to offspring's later mean arterial pressure. In conclusion, this systematic review found suggestive, but still limited, evidence for an association between MPBW with offspring's later BP. The available data suggest that the effect might be mainly mediated via offspring's anthropometry.