Pork Consumption and Its Relationship to Human Nutrition and Health: A Scoping Review a

: Pork is a frequently consumed red meat that provides substantial amounts of energy, macronutrients, and micro-nutrients to the diet. Its role in human nutrition and health is controversial, and a plethora of data exist in the peer-reviewed scientific literature. Therefore, we conducted a scoping review of clinical and population-based studies to assess the effects of pork consumption on human nutrition and health. Results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Data were extracted from 86 studies, including 16 randomized controlled trials, 1 uncontrolled trial, 7 cohort studies, 4 nonrandomized controlled trials, 4 case-cohort and nested case-control studies, 33 case-control studies, and 21 cross-sectional studies. Intervention studies were conducted in healthy individuals and were short ( < 1 mo) to moderate (1 to 6 mo) in duration. The effect of pork intake on patients ’ nutrient status was the most commonly assessed outcome. Most observational studies assessed the effect of pork on cancer incidence, but no studies assessed the effects of pork on cognition or inflammation/oxidative stress. No interventional studies explored diabetes mellitus risk, and only 1 study assessed cancer risk associated with pork consumption. Several micro-nutrients in pork, including zinc, iron, selenium, choline, thiamin, and vitamins B 6 and vitamin B 12 , are thought to influence cognitive function, and this may prove to be an exciting area of emerging research. To date, there is a dearth of high-quality randomized controlled trials assessing the effects of pork intake on disease risk factors and outcomes. The scientific literature contains mostly observational studies, a large majority being case-controlled and cross-sectional analyses. Of note, there is a lack of studies examining isolated effects of processed pork intake on human health. Future clinical trials should address the role of pork consumption in health outcomes, intermediate outcomes, and validated biomarkers.


Introduction
Pork is a red meat that is consumed frequently across the globe.Cross-sectional analyses of the 2006-2016 United States National Health and Nutrition Examination Survey data sets showed that approximately 19.4%, 16.5%, and 16.1% of adults in the U.S. consume pork, fresh pork, and fresh lean pork, respectively (An et al., 2019).Both pork tenderloin and pork sirloin meet the American Heart Association (2021) Heart Health Checkmark criteria, which means that they contain ≤5 g of fat, ≤2 g of saturated fat, and ≤480 mg of sodium per label serving.A 4-ounce raw, boneless, lean pork chop (top loin) provides approximately 144 kcal of energy, 25.3 g of protein, 3.86 g of fat (1.36 g of saturated fat), and substantial amounts of iron, zinc, selenium, magnesium, phosphorus, potassium, thiamin, riboflavin, niacin, pantothenic acid, choline, and vitamins B 6 and B 12 to the diet (FoodData Central identifier 168251) (U.S.Department of Agriculture Agricultural Research Service, 2019).Increased lean pork rather than total pork intake was recently associated with improved nutrient intakes of protein, magnesium, potassium, selenium, zinc, phosphorus, thiamin, riboflavin, niacin, and vitamin B 6 and with lesser increases in daily total energy, saturated fat, and sodium intakes among U.S. adults (An et al., 2019).Aside from the effects of pork on nutrient intakes, there is a plethora of scientific evidence regarding the effects of pork intake on human nutrition and health.Recent randomized controlled trials have shown that the addition of lean pork to both the Mediterranean diet and the Dietary Approaches to Stop Hypertension diet does not affect the demonstrated benefits of these diets on established biomarkers of cardiovascular disease (Sayer et al., 2015;Wade et al., 2019).The addition of an average of 3 servings of lean pork to a Mediterranean-style diet pattern in older adults has been suggested to improve cognitive outcomes (Wade et al., 2019).However, evidence on the health effects of pork is heterogenous and in many cases conflicting.
The use of systematic methodologies for reviewing evidence continues to increase in the nutrition science field.Scoping reviews (otherwise known as evidence mapping) are a relatively new and important tool used to systematically characterize the range of research activity in broad topic areas and are used to guide research priority setting and whether evidence is sufficient for systematic reviews and meta-analyses.They are less exhaustive but utilize rigorous systematic and replicable methodologies that allow for a better understanding of the extent and distribution of evidence in a broad area, highlighting where evidence and evidence gaps exist (Hetrick et al., 2010;Althuis and Weed, 2013;Wang et al., 2016).Although scoping reviews are conducted for different purposes compared with systematic reviews, they are still rigorous and transparent in their methodology to ensure trustworthy results (Munn et al., 2018).Purposes for conducting a scoping review may include the following: (1) to identify the types of available evidence in a given field, (2) to clarify concepts and definitions in the scientific literature, (3) to examine how research is conducted on a certain topic or in a certain field, (4) to identify key characteristics or factors related to a concept, (5) to serve as a precursor to systematic review, and/or (6) to pinpoint and analyze knowledge gaps (Arksey and O'Malley, 2005;Anderson et al., 2008;Levac et al., 2010;Peters et al., 2015;Wang et al., 2016;Munn et al., 2018).Scoping reviews are also extremely useful in helping groups prioritize research agendas, particularly when resources are limited and a plethora of heterogenous evidence exists.
Therefore, our research objective was to conduct a scoping review of clinical and population-based studies assessing the effects of pork consumption in relation to human nutrition and health.

Materials and Methods
We created a literature database and performed evidence mapping following methods described elsewhere (Wang et al., 2016).We reported the results according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (Tricco et al., 2018).

Definitions of fresh, processed, and mixed pork
The American Meat Science Association (AMSA) Lexicon for the standardization of various terms used in meat sciences was adopted for these analyses (Seman et al., 2018).Fresh pork was defined as products that met the AMSA standards for "minimal processing," wherein raw, uncooked meat products have not been significantly altered compositionally and contain no added ingredients but may have been reduced in size by fabrication, mincing, grinding, and/or a meat recovery system (Seman et al., 2018).Processed pork was defined as products that met the AMSA standards for "further processing," which entails any process wherein meat products undergo a transformation, beyond minimal processing, containing approved ingredients and may be subjected to a preservation or processing step(s) through the application of salting, curing, fermentation, thermal processing (smoking and/or cooking), batter/ breading, or other processes to enhance sensory, quality, and safety attributes.These products may include readyto-cook and ready-to-eat products (Seman et al., 2018).Mixed pork was defined as a combination of fresh and processed pork.
Cochrane Central from 1910 to present (Appendix A).No restrictions were set regarding languages or outcome terms.Additional articles were found via reference mining.
After duplicated citations were removed in Endnote, we uploaded titles and abstracts to Rayyan (https:// rayyan.qcri.org)for double independent abstract screening.Two independent reviewers screened all abstracts to exclude irrelevant abstracts such as narrative reviews, systematic reviews, case studies, letters to the editor, ecological studies, and conference proceedings or abstracts.We included studies conducted in participants of all ages looking at pork consumption compared with any comparator.Because many study population details were not described in the abstracts, we only excluded those abstracts that clearly stated nonpork primary exposures and outcomes not related to health or nutrition.We then retrieved the full-text articles of all potentially relevant abstracts and performed full-text screening according to our inclusion and exclusion criteria (Table 1).Two reviewers discussed all discrepancies and disagreements during both abstract and full-text screening phases and resolved discrepancies via consensus.If no consensus could be reached, a third reviewer or the entire research team resolved the remaining discrepancies.We recorded the primary reason for exclusion of all full-text articles (Appendix B).Studies in Appendix B were "set aside due to processed meat" if they did not specify whether the processed meat was pork or other meat.

Data extraction
We performed data extraction on all included fulltext articles.We extracted information on study characteristics (i.e., study design and sample size), study participant characteristics (i.e., age, health status, and gender), intervention characteristics (i.e., pork source, dose, and form of administration), and a list of analyzed outcomes.Data were extracted by one reviewer and spot checked by a second team member.
We did not perform a risk-of-bias assessment of included studies in the scoping review.

Data analysis and charting
We used one study as our unit of analysis.We treated multiple studies reported in one publication as separate studies in the analysis.To allow for frequency analysis and identification of research gaps, outcomes were classified into categories based on biomarkers and indicators for health outcomes.The outcome categories were cancer, cardiovascular disease risk, diabetes risk, cognitive function, weight status and body composition, nutrient status, inflammation, oxidative stress, and other (Table 2).All other health outcomes that could not be grouped into these predefined outcome categories were grouped into an "other" outcome category.
To summarize the characteristics of the included studies, we conducted descriptive analyses on study design, country, sample size, study population To visualize gaps in research, we created bubble plots (a type of weighted scatterplot) grouping studies by health outcome, study design, and pork category (fresh pork, processed pork, and mixed sources).

Results
We screened a total of 1,967 abstracts identified through literature searches in the Medline, Cochrane, and Embase databases.A total of 318 full-text articles were retrieved for full-text screening.After excluding 194 articles (see Appendix B for exclusion reasons), we included 126 studies (published in 124 articles) for data extraction.Of these 126 articles, we set aside 40 (see Appendix B for exclusion reasons).

Study characteristics
Many studies investigated the effects of pork consumption on various outcome categories.Figure 2 shows the cumulative frequency of studies published every 5 y from 1988 to 2020.As shown in Figure 2, there was a significant increasing trend in the number of publications reporting cancer outcomes from 1988

Interventional studies
Among the 85 included studies, 21 were interventional studies (Table 3).Of these, 76.19% were randomized control trials, 19.05% were nonrandomized control trials, and 4.76% were uncontrolled trials.Of the included interventional studies, the average participant's mean age was 39.51 y (range, 1.49 to 82.69 y).Most studies had a duration of 1 to 6 mo (52.38%); 28.57% of studies were >1 mo in duration, whereas only 3 studies were longer than 6 mo.Within the 4 pork intervention categories, 28.57% were exclusive fresh meat, 14.29% provided only processed meat, 38.10% were mixed pork sources, and the other studies (19.05%) did not specify pork category.The majority of funding sources came from industry (33.33%) and mixed sources (38.10%).One-third of the interventional studies were conducted in Europe, 28.57% in North America, and 23.81% in Oceania.Only a few articles were from China (9.52%) and other Asian countries (4.76%).Nutrition status was the most frequently studied outcome among interventional studies, followed by weight status and body composition (28.57%) and cardiovascular heart disease risk (28.57%).Some studies focused on inflammation (14.29%), cancer (4.76%), and cognitive function (4.76%), whereas 38.1% studied other outcomes.Only 3 interventional studies isolated effects of processed pork intake.

Observational studies
A total number of 64 observational studies were included.Most were cross-sectional studies and casecontrol studies (82.81%).Cohort studies (17.19%) include prospective and retrospective cohort studies, case-cohort studies, and nested case-control studies (Table 4).The average participant's mean age was 53.7 y.About half of the included studies specified the type of pork exposure.For instance, 15.62% reported fresh pork as the only exposure, 9.38% reported processed pork exposure only (i.e., bacon, ham, and other processed pork product), and 25% reported mixed exposure of fresh and processed pork.More than half of the included studies reported the funding source.Of these, 7.81% were supported by multiple funding resources.As for studies reporting a single funding source, government funding was the most common (29.69%), followed by nonprofit (9.38%) and industry (6.25%) funding.Included studies were conducted across the globe, with 32.81% conducted in North American countries, 26.56% in European countries, and 20.31% in China.No cohort studies were identified as being conducted in the South America region or the Oceania region.The most commonly reported outcome was cancer (60.9%), followed by cardiovascular disease risk factors (10.93%) and weight status and body composition outcome (7.81%).Cancer and weight status and body composition were the only 2 outcomes reported in cohort studies.Only 6 case-control and 6 cross-sectional studies isolated effects of processed pork intake, with the large majority focusing on cancer incidence.

Identifying research gaps related to study design and pork categorization
Figure 3 shows the differences in outcome categories explored by interventional studies and observational studies.Nutrient status outcomes were the most frequently explored in interventional studies.These included nutrient status biomarkers for protein/amino acids, folate iron, vitamin B 6 , vitamin B 12 , and zinc.We did not find studies assessing pork's contribution to selenium or thiamin status.Cancer outcomes were the most frequently explored in observational studies.Very few observational studies explored inflammation, oxidative stress, or cognitive function associated with pork consumption.Only one interventional study assessed the role of pork intake with cancer outcomes.As expected, sample sizes were much larger for observational studies compared with interventional studies.
Figure 4 shows the differences in health outcomes reported by categorization of pork as fresh pork, processed pork, and mixed pork sources.Studies that included fresh pork as the main exposure of interest reported on almost all outcome categories, with the largest number of fresh pork studies reporting on cancer risk.Studies that included processed pork as the main exposure of interest primarily reported on cancer risk, with 1 study reporting on weight status and body composition and 1 study reporting on cardiovascular disease risk.Studies that included mixed pork sources as the main exposure of interest reported on all outcomes, and cancer was the most frequently investigated outcome.Figure 5 shows differences in cancer outcome sites reported by categorization of pork as fresh pork, processed pork, and mixed pork sources.Cancers of the gastrointestinal tract were frequent sites to be assessed across observational studies.

Discussion
Scoping reviews are a replicable, systematic, and evidence-based approach used to identify, collect, and evaluate the characteristics of the existing peerreviewed literature.Here, we highlight research gaps and opportunities for systematic reviews in relation to the effects of pork consumption on human nutrition and health.The scientific literature contains mostly observational studies, a large majority being casecontrolled and cross-sectional analyses.To date, there are a dearth of high-quality randomized controlled trials assessing effects of pork intake on disease risk factors and outcomes.The effect of pork intake on patients' nutrient status was the most assessed outcome.No interventional studies explored diabetes mellitus risk, and only 1 study assessed cancer risk associated with pork consumption.The single "cancer risk" intervention sought to investigate whether cured meat modulates biomarkers of cancer risk and whether specific agents can suppress cured meat-induced preneoplastic lesions in rats and associated biomarkers in rats and humans.Data from this study suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured meat intake among observational studies (Pierre et al., 2013).Along the same lines, regular consumption of biopeptides contained in dry-cured ham but absent in cooked ham were shown to impair platelet and monocyte activation and levels of plasmatic P-selected, monocyte chemoattractant protein-1 and interleukin-6 in healthy subjects (Martínez-Sánchez et al., 2017).Surprisingly, there was a dearth of observational studies and absence of    prospective cohort studies that examined the role of processed pork on cancer incidence and other health outcomes.Many food frequency questionnaires (FFQ) used in observational analyses are currently not able to quantify intake of fresh and processed pork.This is an important research gap that needs to be addressed among FFQ and when designing future observational research.
Although rural Chinese toddlers consuming fortified cereal had higher vitamin B 12 levels in one study, those receiving 50 g of pork per day had higher cognitive scores (Sheng et al., 2019).However, a separate quasi-experimental study did not find any advantages of pork versus chicken on cognitive function in healthy older adults, suggesting that the type of dietary protein during aging may not impact cognitive function (Charlton et al., 2016).The inclusion of 2 to 3 weekly servings of fresh, lean pork in the Mediterranean diet was shown to lead to improved cognitive performance over a 24-wk period, as indicated by higher processing speed performance and emotional role functioning.The Mediterranean diet, which is rich in high-selenium foods such as seafood and nuts, has been associated with a lower risk of age-related cognitive decline (Scarmeas et al., 2006;Hardman et al., 2016).Several micronutrients in pork, including zinc, iron, selenium, choline, thiamin, and vitamins B 6 and vitamin B 12 , are thought to influence cognitive function and may prove to be an exciting emerging area of research.Future prospective cohort investigations could greatly help in the design of larger, long-duration randomized clinical trials that assess outcomes (e.g., Alzheimer's dementia incidence).
Most observational studies assessed the effect of pork on cancer incidence, followed by cardiovascular disease, weight status and body composition, type 2 diabetes, and nutrient status.No prospective cohort studies assessed the effects of pork on cardiovascular disease, type 2 diabetes, cognition, inflammation/oxidative stress, or nutrient status.
Our study has several strengths and weaknesses.The main strength of this review is the thorough, systematic search strategy and detailed analysis of characteristics reported in the included studies.This review is limited by the availability of manuscripts to online searches in the English language.Another limitation important to note is that scoping reviews do not typically include quality (risk of bias) appraisal of included studies, and therefore there can be substantial amounts of poor-quality research.Observational studies failed to indicate whether the AMSA lexicon for "minimal processing and "further processing" was adopted, in the same way we categorized products as "fresh" or "processed" pork.The inability of current FFQ to distinguish between fresh and processed pork poses additional major limitations to our analyses.

Conclusions
Few conclusions can be drawn from studies evaluating the effects of pork on human nutrition and health.Several micronutrients in pork, including zinc, iron, selenium, choline, thiamin, and vitamins B 6 and vitamin B 12 , are thought to influence cognitive function, and this may prove to be an exciting area of emerging research.To date, there is a dearth of high-quality randomized controlled trials assessing the effects of pork intake on disease risk factors and outcomes.The scientific literature contains mostly observational studies, a large majority being case-controlled and crosssectional analyses.Of note, there is a lack of studies examining isolated effects of processed pork intake on human health.Future clinical trials should address the role of pork consumption in health outcomes, intermediate outcomes, and validated biomarkers.
to 2020.Meanwhile, the number of publications reporting cardiovascular disease risk and nutrient status outcomes experienced a steady increase.The research published in other outcome categories, including diabetes mellitus risk factors, weight status and body composition, cognitive function, and inflammation and oxidative stress, emerged at the beginning of the 21st century and has increased since then.

Figure 1 .
Figure 1.Literature search and study selection process.RCT = randomized controlled trial.

Figure 2 .
Figure 2. Cumulative frequency of published studies by outcome categories.CVD = cardiovascular disease; DM = diabetes mellitus.

Figure 4 .
Figure 4. Bubble plot of health outcome categories by pork categorization.Each bubble in the figure represents one study, and the size of the bubble is proportional to the study sample size.Categories specified as "other" were not included in this bubble plot.CVD = cardiovascular disease; DM = diabetes mellitus.

Figure 3 .
Figure 3. Bubble plot of health outcome categories by study design.Each bubble in the figure represents one study, and the size of the bubble is proportional to the study sample size.CVD = cardiovascular disease; DM = diabetes mellitus.

Figure 5 .
Figure 5. Bubble plot of cancer outcome sites by pork categorization.Each bubble in the figure represents one study, and the size of the bubble is proportional to the study sample size.

Table 1 .
Study eligibility criteria for full-text screening characteristics, health outcome categories assessed in the studies, and funding source.

Table 3 .
Summary of study characteristics of interventional studies

Table 3 .
(Continued ) Mean age represents the average of the reported mean age for each included study.The median age was used if the mean age was not reported.The midpoint of the reported age range was used if neither mean age nor median age was reported.One study did not report mean age, median age, or age range.≤20% of the population have diseases.cWith disease conditions: >20% of the population have diseases.
a b Generally healthy:

Table 4 .
Summary of study characteristics of observational studies Mean age represents the average of reported mean age for each included study.The median age was used if the mean age was not reported.The midpoint of the reported age range was used if neither mean age nor median age was reported.Fifteen studies did not report mean age, median age, or age range.Some studies examined multiple outcomes, which generates percentages that sum to >100%.NA = not applicable.
b c Generally healthy: ≤20% of the population have diseases.d With disease conditions: >20% of the population have diseases.e