Dietary Recommendations for Familial Hypercholesterolaemia: an Evidence-Free Zone
by David M Diamond, et al
- Current dietary guidelines for management of coronary heart disease (CHD) risk in familial hypercholesterolaemia (FH) are based on the diet-heart hypothesis, which is outdated and unsupported.
- There is no evidence to support the recommendation that FH individuals should consume a low saturated fat, low cholesterol diet.
- A low carbohydrate diet (LCD) significantly improves cardiovascular disease biomarkers, compared with a low fat diet.
- There is sufficient rationale for conducting clinical trials to assess the effects of an LCD on FH individuals with an insulin-resistant phenotype.
- Extensive research has documented that hypercoagulation is a more important risk factor for CHD than low-density lipoprotein cholesterol in FH. Therefore, LCD trials should include FH subjects with an elevated risk of hypercoagulation.
Consumption of Unprocessed Red Meat Is Not a Risk to Health
from World Farmers’ Organisation (WFO) Scientific Council
A synopsis of five significant, recent and broad-scale scientific investigations on the health risks and health benefits of red meat consumption indicates that there is no convincing scientific evidence for assertions about harmful health effects of unprocessed red meat intake. If at all, the data very slightly lean toward an association of red meat consumption and protective health benefits. Overall, any of the statistical associations of up to 100 grams of red meat consumption per capita per day are so weak that they should be considered neutral. It is notable that less than 1% of the global population consumes more than 85 grams of red meat per day. From a global public health perspective, then, red meat consumption above the threshold of 85 grams is so negligible as to be irrelevant. National governments and supranational organizations such as the EU and UN, and their initiatives such as this year’s UN Food Systems Summit, as well as international business and consumer associations, would be wrong to assume that a scientific consensus exists to justify policies to reduce red meat consumption in the general population for health reasons.
Associations of unprocessed and processed meat intake with mortality and cardiovascular disease in 21 countries [Prospective Urban Rural Epidemiology (PURE) Study]: a prospective cohort study
by Romaina Iqbal, et al
In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD.
We conducted an in-depth analysis of prospective, retrospective, case-control and cohort studies, systematic review articles, and IARC monograph reports, which revealed that the IARC/WHO report weighted the results of studies based in Western countries more and that the correlation between intake of processed meat products and colorectal cancer incidence in Asians is not clearly supported. Among 73 epidemiological studies, approximately 76% were conducted in Western countries, whereas only 15% of studies were conducted in Asia. Furthermore, most studies conducted in Asia showed that processed meat consumption is not related to the onset of cancer. Moreover, there have been no reports showing significant correlation between various factors that directly or indirectly affect colorectal cancer incidence, including processed meat products types, raw meat types, or cooking methods.
Red meat and colon cancer: A review of mechanistic evidence for heme in the context of risk assessment methodology
by Claire Kruger & Yuting Zhou
In conclusion, the methodologies employed in current studies of heme have not provided sufficient documentation that the mechanisms studied would contribute to an increased risk of promotion of preneoplasia or colon cancer at usual dietary intakes of red meat in the context of a normal diet.
Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.”
No association between meat intake and mortality in Asian countries
by Dominik D Alexander
After pooling data across the cohorts, Lee et al (3) observed no significant increases in risk of all-cause mortality comparing the highest with the lowest intake categories of total meat, red meat, poultry, or fish. In contrast, most associations were in the inverse direction with significant decreased risks for poultry (among men and women) and fish (women), with a nearly significant decreased risk with greater intakes of red meat in women (upper CI: 1.00). Similar patterns of associations (most indicating a decreased risk) were observed for cause-specific mortality; comparing the highest with the lowest intake categories, significant decreased risks of CVD mortality with red meat (men) and cancer mortality with red meat and poultry (women) were observed. The only significant positive association in the overall analyses was for the highest category of fish intake and cancer mortality. Little effect modification was apparent after stratification by educational level and by BMI.
Researchers in Korea have discovered that the link between meat consumption and colorectal cancer may not apply to Asians. The meat-colorectal cancer correlation was first elucidated in a report by the International Agency for Research on Cancer (IARC) in 2015. The Korean researchers carried out a thorough review of over 500 studies that had previously been conducted on meat consumption and cancer. These included cohort and case-control analyses, prospective and retrospective studies, other review articles, as well as IARC monograph reports. Of these, 73 human epidemiological studies were selected for more in-depth analysis.
“The aim was to investigate the relationship between meat intake and colorectal cancer risk from an Asian, particularly Korean, perspective,” said the authors. “[We found] that approximately 76% [of the studies] were conducted in Western countries, whereas only 15% of studies were conducted in Asia. Furthermore, most studies conducted in Asia showed that processed meat consumption is not related to the onset of cancer.” “[As such], the correlation between intake of processed meat products and colorectal cancer incidence in Asians is not clearly supported,” they concluded. The study also reported that there do not exist any conclusive reports proving a significant correlation between meat consumption and colorectal cancer, whether it involves processed meats, raw meats or the relevant cooking methods.
Recommendations: The panel suggests that adults continue current unprocessed red meat consumption (weak recommendation, low-certainty evidence). Similarly, the panel suggests adults continue current processed meat consumption (weak recommendation, low-certainty evidence). […]
Contemporary dietary guidelines recommend limiting consumption of unprocessed red meat and processed meat. For example, the 2015–2020 Dietary Guidelines for Americans recommend limiting red meat intake, including processed meat, to approximately 1 weekly serving (1). Similarly, United Kingdom dietary guidelines endorse limiting the intake of both red and processed meat to 70 g/d (2), and the World Cancer Research Fund/American Institute for Cancer Research recommend limiting red meat consumption to moderate amounts and consuming very little processed meat (3). The World Health Organization International Agency for Research on Cancer has indicated that consumption of red meat is “probably carcinogenic” to humans, whereas processed meat is considered “carcinogenic” to humans (4). “These recommendations are, however, primarily based on observational studies that are at high risk for confounding and thus are limited in establishing causal inferences, nor do they report the absolute magnitude of any possible effects. Furthermore, the organizations that produce guidelines did not conduct or access rigorous systematic reviews of the evidence, were limited in addressing conflicts of interest, and did not explicitly address population values and preferences, raising questions regarding adherence to guideline standards for trustworthiness (5–9). […]
In our assessment of causal inferences on unprocessed red meat and processed meat and adverse health outcomes, we found that the absolute effect estimates for red meat and processed meat intake (13, 16) were smaller than those from dietary pattern estimates (14), indicating that meat consumption is unlikely to be a causal factor of adverse health outcomes (Table 1).
Should dietary guidelines recommend low red meat intake?
by Frédéric Leroy & Cofnas
3. Meat eating and chronic disease: evaluation of the evidence
3.1. Evidence from observational studies needs to be interpreted with care
As a first point of concern, the input data obtained from food frequency questionnaires should be interpreted prudently as they can be problematic for a variety of reasons (Schatzkin et al., 2003; Archer et al., 2018; Feinman, 2018). Social desirability bias in food reporting is just one example, as reported consumption can be affected by the perceived health status of certain foods. Not all self-defined vegetarians avoid meat, which is suggestive of a considerable risk for underreported intake in health-conscious groups (Haddad & Tanzman, 2003).
Secondly, diets are difficult to disentangle from other lifestyle factors. It has been shown that Western-style meat eating is closely associated with nutrient-poor diets, obesity, smoking, and limited physical activity (Alexander et al., 2015; Fogelholm et al., 2015; Grosso et al., 2017; Turner & Lloyd, 2017). Given the fact that health authorities have been intensely promoting the view that meat is unhealthy, health-conscious people may be inclined to reduce intake. Typically, the associations between meat eating and disease tend to be higher in North American than in European or Asian cohort studies, indicating the presence of lifestyle bias and the need for cross-cultural assessments (Wang et al., 2016; Grosso et al., 2017; Hur et al., 2018). A pooled analysis of prospective cohort studies in Asian countries even indicated that red meat intake was associated with lower cardiovascular mortality in men and cancer mortality in women (Lee et al., 2013). Likewise, when omitting Seventh-Day Adventist studies from meta-analyses, the beneficial associations with cardiovascular health for vegetarian diets are either less pronounced or absent indicating the specific effects of health-conscious lifestyle rather than low meat consumption as such (Kwok et al., 2014; FCN, 2018). This is important, as Seventh-Day Adventism has had considerable influence on dietary advice worldwide (Banta et al., 2018).
As a third point, the relative risks (RRs) obtained from observational studies are generally low, i.e., much below 2. In view of the profusion of false-positive findings and the large uncertainty and bias in the data due to the problems mentioned above (Boffetta et al., 2008; Young & Karr, 2011), such low RR levels in isolation would not be treated as strong evidence in most epidemiological research outside nutrition (Shapiro, 2004; Klurfeld, 2015). Relationships with RRs below 2, which are susceptible to confounding, can be indicative but should always be validated by other means, such as randomized controlled trials (RCTs) (Gerstein et al., 2019). The association between meat eating and colorectal cancer, for instance, leads to an RR estimate below 1.2, whereas for the association between visceral fat and colorectal neoplasia this value equals 5.9 (Yamamoto et al., 2010). The latter provides a robust case that is much more deserving of priority treatment in health policy development. […]
3.2. Intervention studies have not been able to indicate unambiguous detrimental effects
As stated by Abete et al. (2014), epidemiological findings on meat eating “should be interpreted with caution due to the high heterogeneity observed in most of the analyses as well as the possibility of residual confounding”. The interactions between meat, overall diet, human physiology (including the gut microbiome), and health outcomes are highly intricate. Within this web of complexity, and in contrast to what is commonly stated in the public domain (Leroy et al., 2018a), the current epidemiological and mechanistic data have not been able to demonstrate a consistent causal link between red meat intake and chronic diseases, such as colorectal cancer (Oostindjer et al., 2014; Turner & Lloyd, 2017).
RCTs can play an important role in establishing causal relationships, and generally provide much stronger evidence than that provided by observational data. However, even RCTs are not fail-safe and can also be prone to a range of serious flaws (Krauss, 2018). Intervention studies that overlook the normal dietary context or use non-robust biomarkers should be interpreted with caution, and do not justify claims that there is a clear link between meat and negative health outcomes (see Turner & Lloyd, 2017; Kruger & Zhou, 2018). The available evidence generally suggests that interventions with red meat do not lead to an elevation of in vivo oxidative stress and inflammation, which are usually cited as being part of the underlying mechanisms triggering chronic diseases (Mann et al., 1997; Hodgson et al., 2007; Turner et al., 2017). Even in an epidemiological cohort study that was suggestive of an inflammatory response based on an increased CRP level, this effect became non-significant upon adjustment for obesity (Montonen et al., 2013). Moreover, a meta-analysis of RCTs has shown that meat eating does not lead to deterioration of cardiovascular risk markers (O’Connor et al., 2017). The highest category of meat eating even paralleled a potentially beneficial increase in HDL-C level. Whereas plant-based diets indeed seem to lower total cholesterol and LDL-C in intervention studies, they also increase triglyceride levels and decrease HDL-C (Yokoyama et al., 2017), which are now often regarded as superior markers of cardiovascular risk (Jeppesen et al., 2001).
Based on the above, we conclude that there is a lack of robust evidence to confirm an unambiguous mechanistic link between meat eating as part of a healthy diet and the development of Western diseases. It is paramount that the available evidence is graded prior to developing policies and guidelines, making use of quality systems such as GRADE (Grading of Recommendations Assessment, Development and Evaluation; Guyatt et al., 2008). One of the founders of the GRADE system has issued a public warning that the scientific case against red meat by the IARC panel of the WHO has been overstated, doing “the public a disservice” (Guyatt, 2015). The IARC’s (2015) claim that red meat is “probably carcinogenic” has never been substantiated. In fact, a risk assessment by Kruger and Zhou (2018) concluded that this is not the case. Such hazard classification systems have been heavily criticized, even by one of the members of the IARC working group on red meat and cancer (Klurfeld, 2018). They are accused of being outmoded and leading to avoidable health scares, public funding of unnecessary research and nutritional programs, loss of beneficial foods, and potentially increased health costs (Boyle et al., 2008; Anonymous, 2016; Boobis et al., 2016).
3.3. A scientific assessment should not overlook conflicting data
Dietary advice that identifies meat as an intrinsic cause of chronic diseases often seems to suffer from cherry-picking (Feinman, 2018). One example of a fact that is typically ignored is that hunter-gatherers are mostly free of cardiometabolic disease although animal products provide the dominant energy source (about two-thirds of caloric intake on average, with some hunter-gatherers obtaining more than 85% of their calories from animal products; Cordain et al., 2000, 2002). In comparison, contemporary Americans obtain only about 30% of calories from animal foods (Rehkamp, 2016).
Whereas per capita consumption of meat has been dropping over the last decades in the US, cardiometabolic diseases such as type-2 diabetes have been rapidly increasing. Although this observation does not resolve the question of causality one way or the other, it should generate some skepticism that meat is the culprit (Feinman, 2018). Moreover, several studies have found either that meat intake has no association with mortality/morbidity, or that meat restriction is association with various negative health outcomes (e.g., Key et al., 2009; Burkert et al., 2014; Kwok et al., 2014; Lippi et al., 2015; Hur et al., 2018; Iguacel et al., 2018; Yen et al., 2018). As another example of conflicting information, the epidemiological association pointing to a potential role of the meat nutrient L-carnitine in atherosclerosis via trimethylamine N-oxide (TMAO) formation (Koeth et al., 2013), is contradicted by intervention studies (Samulak et al., 2019) and epidemiological data showing that fish intake, being by orders of magnitude the largest supplier of TMAO (Zhang et al., 1999), improves triglycerides and HDL levels (Alhassan et al., 2017). […]
5. Meat avoidance leads to a loss of nutritional robustness
Diets poor in animal source foods can lead to various nutritional deficiencies, as already described more than a century ago for the case of pellagra (Morabia, 2008), a condition which remains relevant today for poorly planned vegan diets (Ng & Neff, 2018). Advocates of vegetarian/vegan diets usually admit that these diets must indeed be “well-planned” in order to be successful, which involves regular supplementation with nutrients such as B12. However, realistically, many people are not diligent about supplementation, and will often dip into deficient or borderline-deficient ranges if they do not obtain nutrients from their regular diet. In such cases, general malnutrition (Ingenbleek & McCully, 2012), poorer health (Burkert et al., 2014), and nutrient limitations (Kim et al., 2018) may be the result, as found in various countries, such as Denmark (Kristensen et al., 2015), Finland (Elorinne et al., 2016), Sweden (Larsson & Johansson, 2002), and Switzerland (Schüpbach et al., 2017). For example, a substantial number of vegetarians and vegans are in the deficient or borderline-deficient range for B12 (Herrmann & Geisel, 2002; Herrmann et al., 2003), despite the fact that the need for B12 supplementation is well-publicized (see also Herbert, 1994; Hokin & Butler, 1999; Donaldson, 2000; Elmadfa & Singer, 2009; Gilsing et al., 2010; Obersby et al., 2013; Pawlak et al. 2013, 2014; Pawlak, 2015; Woo et al., 2014; Naik et al., 2018). B12 deficiency is particularly dangerous during pregnancy (Specker et al., 1988, 1990; Bjørke Monsen et al., 2001; Koebnick et al., 2004), childhood (Rogers et al., 2003) and adolescence (van Dusseldorp et al., 1999; Louwman et al., 2000).
Other potentially challenging micronutrients for people on plant-based diets include (but are not limited to) iodine (Krajcovicová-Kudlácková et al., 2008; Leung et al., 2011; Brantsaeter et al., 2018), iron (Wilson & Ball, 1999; Wongprachum et al., 2012; Awidi et al., 2018), selenium (Schultz & Leklem, 1983; Kadrabová et al., 1995), and zinc (Foster et al., 2013). Even if plant-based diets contain alpha linolenic acid, this may not (as noted) prevent deficiencies in the long-chain omega-3 fatty acids EPA and DHA (Rosell et al., 2005), which can pose serious risks in pregnancy and for growing children (Burdge et al., 2017; Cofnas, 2019).
Risks of nutritional deficiency are also documented by an extensive list of clinical case reports in the medical literature, with serious and sometimes irreversible pathological symptoms being reported for infants (e.g., Shinwell & Gorodisher, 1982; Zengin et al., 2009; Guez et al., 2012; Bravo et al., 2014; Kocaoglu et al., 2014; Goraya et al., 2015), children (e.g., Colev et al., 2004; Crawford & Say, 2013), adolescents (e.g., Chiron et al., 2001; Licht et al., 2001; O’Gorman et al., 2002), and adults (e.g., Milea et al., 2000; Brocadello et al., 2007; De Rosa et al., 2012; Førland & Lindberg, 2015). The latter reports commonly refer to failure to thrive, hyperparathyroidism, macrocytic anemia, optic and other neuropathies, lethargy, degeneration of the spinal cord, cerebral atrophy, and other serious conditions. Although the direction of causality is not clear, meat avoidance is statistically associated with eating disorders and depression (Zhang et al., 2017; Barthels et al., 2018; Hibbeln et al., 2018; Matta et al., 2018; Nezlek et al., 2018) and may mirror neurological problems (Kapoor et al., 2017).
Our main concern is that avoiding or minimizing meat consumption too strictly may compromise the delivery of nutrients, especially in children and other vulnerable populations. Evidently, health effects of plant-based approaches depend largely on the dietary composition (Satija et al., 2016). Yet, the more restricted the diet and the younger the age, the more this will be a point of attention (Van Winckel et al., 2011). According to Cofnas (2019), however, even realistic vegetarian diets that include diligent supplementation can put children at risk for deficiencies and thereby compromise health in both the short and long term. There is some direct and indirect evidence that the elevated phytoestrogen intake associated with low-meat diets may pose risks for the development of the brain and reproductive system (Cofnas, 2019). Moreover, attempts to introduce dietary modifications that are also compatible with vegan philosophy often pose a medicosocial challenge (Shinwell & Gorodischer, 1982). In our opinion, the official endorsement of diets that avoid animal products as healthy options is posing a risk that policy makers should not be taking. As stated by Giannini et al. (2006): “It is alarming in a developed country to find situations in which a child’s health is put at risk by malnutrition, not through economic problems but because of the ideological choices of the parents”.
Dietary Risk Factors for Heart Disease and Cancer
Blue Zones Dietary Myth
Eat Beef and Bacon!
Are ‘vegetarians’ or ‘carnivores’ healthier?
Vegetarianism is an Animal-Based Diet
Being “mostly vegan” is like being “a little pregnant.”
Plant-Based Nutritional Deficiencies
True Vitamin A For Health And Happiness
Hubris of Nutritionism
Ancient Greek View on Olive Oil as Part of the Healthy Mediterranean Diet
Wild-Caught Salmon and Metabolic Health
Early Research On the Industrial Diet
Moral Panic and Physical Degeneration
Health From Generation To Generation