Dietary Fats and Atherosclerotic Cardiovascular Disease: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Nutrition & Dietetics
Contributor:
Andrea Baragetti

The favorable transition from hominids to homo sapiens during evolution prompted changes in the physiological functions and immune competences (including survival to pathogens and infections) to adapt to the intake of high-energy containing foods, principally dietary fats. Today, the access to a variety of highly-caloric fatty foods is hardly balanced by energy consumption. As a consequence, the dominant genetic pathways evolved to favor the intake of calorie-rich diets and the storage of energy as fats in the adipose tissue are in some circumstances redundant, especially in affluent societies, giving rise to obesity, diabetes and cardiovascular disease (CVD)-comorbidities. Current guidelines recommend reducing the daily intake of dietary fats for the prevention of ischemic cardiovascular diseases (CVDs).

  • dietary lipids
  • immune-inflammation
  • cardiovascular disease
  • microbiota

1. Introduction

The favorable transition from hominids to homo sapiens during evolution [1] prompted changes in the physiological functions and immune competences (including survival to pathogens and infections) to adapt to the intake of high-energy containing foods, principally dietary fats [2]. Today, the access to a variety of highly-caloric fatty foods is hardly balanced by energy consumption. As a consequence, the dominant genetic pathways evolved to favor the intake of calorie-rich diets and the storage of energy as fats in the adipose tissue are in some circumstances redundant, especially in affluent societies, giving rise to obesity, diabetes and cardiovascular disease (CVD)-comorbidities.
Currently, the Western lifestyle, including dietary habits, is believed to contribute a chronic state of low-grade inflammation [3] that eventually prompts the development of atherosclerosis, the etiopathological factor of ischemic CVDs. Of note is that the connection between the Western dietary lifestyle and onset of CVDs has been demonstrated to impact morbidity and mortality worldwide [4].
Dietary interventions are considered the first approach in preventing atherosclerotic CVDs. All guidelines, while recommending reduction of fat consumption, also advise avoidance of dietary trans-fats, reducing the intake of saturated fats, and preferring mono or poly-unsaturated long-chain fats [5]. Achieving these goals remains a challenge for physicians and patients. Furthermore, the level of evidence for these recommendations is backed-up by single randomized clinical trials [6] and mostly relies upon large non-randomized observational studies [7], which suffer from confounding [8] and difficulties in quantitatively measuring dietary intake [9].
In addition, other factors linked to dietary consumption which are less likely to be captured in epidemiological studies have emerged as being associated with the risk of atherosclerotic CVD, and include the type of food availability, personal knowledge of the impact of diet on health, and socio-economic status [10]. As an example, the availability of processed foods is associated with an increased risk of CVDs [11]; this is the case of fat-rich processed meats, whose consumption increases the risk of CVD as compared to fat-rich unprocessed meats [12], fatty fish, and poultry [13], whose consumption is not considered a CVD risk modifier.
Furthermore, in modern societies, we are continuously exposed to postprandial lipemia (PPL) [14], a condition that appears to be causally related to the risk of coronary artery disease [15], myocardial infarction, ischemic heart disease, and ischemic stroke [16]. The mechanisms by which an exaggerated PPL links to CVDs include the fostering of endothelial dysfunction [17][18][19], arterial inflammation, and a pro-atherogenic activation of myeloid cells [18]. In addition, the magnitude of PPL in response to high-fat- based meals in humans appears to be significantly affected by the taxonomic composition of intestinal microbiota [20], which also cross-talk with hematopoietic niches [21], ensuring the activity of the innate immune check-points in the intestine and lymphatics. Once absorbed in the intestine, the majority of dietary fats cross over a complex surveillance system (including the cells patrolling at the interface between enterocytes and lacteals like the mesenteric lymph node (MLN), as opposed to the carbohydrates, sugars, dietary amino acids, protein-rich foods and other dietary components that are believed to exert other pathophysiological mechanisms that do not engage these immune checkpoints [22][23][24][25].

2. Dietary Fats, Inflammation and Atherosclerosis

In the human body, dietary fats face a complex metabolic journey involving a number of cellular checkpoints (Figure 1).
/media/item_content/202111/618dcd9b5d45bnutrients-13-03768-g001.png
Figure 1. The routes for the absorption and the principal immune-inflammatory engagements of dietary lipids in intestinal villi, in the lacteals, MLN up to the liver. MLN = mesenteric lymph node; LDs: lipid droplets; SFAs: saturated fats; MUFA: mono-unsaturated fats; PUFA: poly-unsaturated fats; SCFAs: short chain fatty acids; MFA = medium chain fatty acids; LPS: lipopolysaccharide; ER: endoplasmic reticulum; LDs = lipid droplets; CM: chylomicrons; VLDL = very low density lipoproteins; HDL = high density lipoproteins; DC = dendritic cells; KCs = Kuppfer cells. Upward red arrows indicate activation of a cell or a pathway; downward green arrows indicate inhibition or regulation of a cell or a pathway. Both upward red and downward green arrows for SCFAs and MFAs carried by albumin in the liver indicate contrasting evidence depending on the type of dietary fat.
Dietary fats (triglycerides, phospholipids and cholesterol) are digested in the upper part of the small intestine by the activity of multiple lipases and then absorbed by the enterocytes [26][27]. In addition, gut resident bacteria can contribute to circulating fats principally by producing short-chain fatty acids (SCFAs) from fibers/complex carbohydrates. For example, Faecalibacterium prausnitzii ferments fibers present in the food matrices of fatty foods (e.g., avocados, tree-nuts and peanuts, where over a third of carbohydrates are fibers) [28] and is the major producer of butyrate. Butyrate is known to regulate hematopoietic activity [21] and to control myeloid pro-inflammatory skewing [29], exerting anti-atherogenic properties [30]. Vice versa, Ruminococcus bromii, which is reduced in subjects with atherosclerosis [31], metabolizes complex carbohydrates (that are present in low-fat foods, including pinto beans, whole grains, and nuts with considerable proportion of fats) into propionate. This SCFA promotes insulin sensitivity and reduces the atherosclerotic burden in mice [32]. Beside the production of SCFAs, other gut microbial species express enzymatic systems that metabolize dietary lipids into inflammatory molecules. Among them, trimethylamine (TMA) lyase, an enzyme that converts dietary phosphatidycholine and choline into TMA, is peculiarly expressed by Eggerthella lenta and Eggerthella timonensis [33][34]. Finally, gut resident Gram-negative commensals (e.g., Escherichia coli, Salmonella minnesota, Salmonella typhimurium) synthetize lipid-containing molecules, such as lipopolysaccharide (LPS), which promote apoptotic signaling and trigger systemic immune-metabolic derangement and inflammation [35][36][37].
Once within the enterocytes, SCFAs directly reach the portal system and the liver where they are readily metabolized, while the majority of absorbed dietary fats are released into the lymphatic tree in large lipoproteins (chylomicrons and very-low density lipoproteins, VLDL) [38] (Figure 1). Fatty acids deriving from the hydrolysis of dietary triglycerides and phospholipids in the intestinal lumen are chaperoned to the intracellular endoplasmic reticulum (ER); there, diacylglycerol O-acyltransferase 1 (DGAT1) promotes their re-incorporation in triglycerides which are then transferred by the microsomial triglyceride transfer protein (MTTP) to nascent apolipoprotein B. In this way, chylomicrons are released by the enterocytes in their basolateral membrane. A small fraction of absorbed cholesterol is esterified by acyl CoA-transferase (ACAT) and packaged into chylomicrons. In the Golgi, other apolipoproteins, including apoCIII, apoCII, apoAV, and apoAIV, are added to chylomicrons, which then enter the bloodstream via the thoracic duct and will be eventually taken up by liver (Figure 1).
In addition to chylomicrons, the intestine also produces a small fraction of high density lipoproteins (HDL), through the activities of ATP binding cassette transporter A-1 (ABCA1) and phospholipid transfer protein (PLTP), which transfer cholesterol and phospholipids to apolipoprotein A-I [39]. It has been proposed that a fraction of HDL produced by the intestine moves to the liver through the portal system and antagonizes the binding of LPS to toll-like receptor 4 (TLR4) on the membrane of Kuppfer cells, liver-resident macrophages involved in the defense against gut-derived exogenous molecules [40], thus preventing the recruitment of pro-inflammatory myeloid cells [41] (Figure 1). Although further investigations are required, these findings are in line with the known anti-inflammatory function of HDL [42].

3. Data Linking Intake of Dietary Fats, Markers of Inflammation, and Risk of CVD

The evidence about the molecular and cellular mechanisms by which dietary fats participate in atherogenesis built up the rationale to unveil the connections between different dietary fats, the markers of systemic inflammation, and the risk of CVDs. Despite this aspect having been extensively discussed, data from both epidemiological studies and interventional clinical trials are, however, scarce and heterogeneous.

3.1. Epidemiological Studies

An overall summary of the results from epidemiological studies on the relationship between the pro- or anti-inflammatory effects of dietary fats and CVD risk is reported in Table 1.
Table 1. Summary of the data from epidemiological studies on the association between dietary intake of fats, circulating markers of systemic inflammation and risk of CVD. ↑: Indicates data showing a positive association between the dietary fat intake and the outcome (either inflammatory markers or CVD risk factors); ↓ indicates data showing a positive association between the dietary fat intake and the outcome (either inflammatory markers or CVD risk factors). ↔ indicates that there are missing or contrasting data regarding association between the dietary fat intake and the outcome (either inflammatory markers or CVD risk factors).

EPIDEMIOLOGICAL STUDIES

Dietary fats

Prevalent Effects on Inflammatory Markers

Effects on CVD Risk/Risk Factors

Trans fats

↑ [43] [44] [45]

↓

↔ [46][47] [48] [49]

↑ [43][46][47][48] [44] [45][50]

↓

↔ [49]

Saturated fats

↔ [46][47] [48] [51][52]

↑ [46]

↔ [47] [48] [50][51]

Monounsaturated fats

↓ [46] [53][54]

↓ [46] [53][54]

↔ [48] [55] [50]

Polyunsaturated fats

↔ [46] [48] [53] [56]

↓ [46] [48] [50] [53] [57][58] [56]

n-3 and derivates

↓ [56] [59][60][61][62]

↔ [63]

↓ [59][64] [61]

↔ [63]

n-6 and derivates

↔ [46]

↓ [46]

Cholesterol

↑ [52]

↔ [65][66][67][68]

↑ [65]

↔ [66][67][68][69]

3.2. Interventional Clinical Trials

Table 2 reports a summary of the results from clinical trials, testing the impact of dietary fat consumption on markers of inflammation and CVD risk factors.
Table 2. Summary of data from interventional studies about the association between dietary intake of lipids, circulating markers of systemic inflammation and risk of cardiovascular diseases. ↑: Indicates data showing a positive association between the dietary intervention and the outcome (either inflammatory markers or CVD risk factors); ↓ indicates data showing a positive association between the dietary intervention and the outcome (either inflammatory markers or CVD risk factors). ↔ indicates that there are missing or contrasting data regarding association between the dietary intervention and the outcome (either inflammatory markers or CVD risk factors).

INTERVENTIONAL TRIALS

Dietary Lipids

Prevalent Effects on Inflammatory Markers

Effects on CVD Risk/Risk Factors

Trans fats

↑ [70]

↔ [71]

↑ [72] [70]

Saturated fats

↑ [73] [74] [75]

↔ [70] [76][77] [78]

↑ [70] [73][76] [74][75][78]

↔ [77]

Monounsaturated fats

↓ [70] [73]

↔ [76][77] [78] [79] [80]

↓ [70] [73][76][77] [78] [79]

Polyunsaturated fats

↓ [74]

↔ [76] [78]

↓ [76] [74][78] [81]

Ω-3 and derivates

↓ [82][83][84][85][86] [80]

↔ [75] [87] [88][89] [90][91]

↓ [75] [83][84][85][86][88]

↔ [82][87] [80][89][90][91]

Ω-6 and derivates

↔ [75] [82]

↔ [75] [82]

Cholesterol

↓ [92]

↑ [93]

↔ [94]

↓ [95]

↑ [94]

This entry is adapted from the peer-reviewed paper 10.3390/nu13113768

References

  1. Aiello, L.C.; Wheeler, P. The Expensive-Tissue Hypothesis: The Brain and the Digestive System in Human and Primate Evolution. Curr. Anthropol. 1995, 36, 199–221.
  2. Holmes, E.; Li, J.V.; Marchesi, J.R.; Nicholson, J.K. Gut Microbiota Composition and Activity in Relation to Host Metabolic Phenotype and Disease Risk. Cell Metab. 2012, 16, 559–564.
  3. Christ, A.; Lauterbach, M.; Latz, E. Western Diet and the Immune System: An Inflammatory Connection. Immunity 2019, 51, 794–811.
  4. Meier, T.; Gräfe, K.; Senn, F.; Sur, P.; Stangl, G.I.; Dawczynski, C.; März, W.; Kleber, M.E.; Lorkowski, S. Cardiovascular mortality attributable to dietary risk factors in 51 countries in the WHO European Region from 1990 to 2016: A systematic analysis of the Global Burden of Disease Study. Eur. J. Epidemiol. 2019, 34, 37–55.
  5. Mach, F.; Baigent, C.; Catapano, A.L.; Koskinas, K.C.; Casula, M.; Badimon, L.; Chapman, M.J.; De Backer, G.G.; Delgado, V.; Ference, B.A.; et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur. Heart J. 2020, 41, 111–188.
  6. Estruch, R.; Ros, E.; Salas-Salvadó, J.; Covas, M.-I.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; Fiol, M.; Lapetra, J.; et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N. Engl. J. Med. 2018, 378, e34.
  7. Satija, A.; Yu, E.; Willett, W.C.; Hu, F.B. Understanding Nutritional Epidemiology and Its Role in Policy. Adv. Nutr. 2015, 6, 5–18.
  8. Maki, K.C.; Slavin, J.L.; Rains, T.M.; Kris-Etherton, P.M. Limitations of Observational Evidence: Implications for Evidence-Based Dietary Recommendations. Adv. Nutr. 2014, 5, 7–15.
  9. Hu, F.B.; Satija, A.; Rimm, E.B.; Spiegelman, D.; Sampson, L.; Rosner, B.; Camargo, C.A.; Stampfer, M.; Willett, W.C. Diet Assessment Methods in the Nurses’ Health Studies and Contribution to Evidence-Based Nutritional Policies and Guidelines. Am. J. Public Health 2016, 106, 1567–1572.
  10. Yusuf, S.; Joseph, P.; Rangarajan, S.; Islam, S.; Mente, A.; Hystad, P.; Brauer, M.; Kutty, V.R.; Gupta, R.; Wielgosz, A.; et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): A prospective cohort study. Lancet 2020, 395, 795–808.
  11. Astrup, A.; Magkos, F.; Bier, D.M.; Brenna, J.T.; de Oliveira Otto, M.C.; Hill, J.O.; King, J.C.; Mente, A.; Ordovas, J.M.; Volek, J.S.; et al. Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2020, 76, 844–857.
  12. O’Connor, L.E.; Kim, J.E.; Campbell, W.W. Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: A systemically searched meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2017, 105, 57–69.
  13. Zhong, V.W.; Van Horn, L.; Greenland, P.; Carnethon, M.R.; Ning, H.; Wilkins, J.T.; Lloyd-Jones, D.M.; Allen, N.B. Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality. JAMA Intern. Med. 2020, 180, 503.
  14. O’Keefe, J.H.; Torres-Acosta, N.; O’Keefe, E.L.; Saeed, I.M.; Lavie, C.J.; Smith, S.E.; Ros, E. A Pesco-Mediterranean Diet With Intermittent Fasting. J. Am. Coll. Cardiol. 2020, 76, 1484–1493.
  15. Patsch, J.R.; Miesenböck, G.; Hopferwieser, T.; Mühlberger, V.; Knapp, E.; Dunn, J.K.; Gotto, A.M.; Patsch, W. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler. Thromb. J. Vasc. Biol. 1992, 12, 1336–1345.
  16. Nordestgaard, B.G.; Benn, M.; Schnohr, P.; Tybjærg-Hansen, A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. J. Am. Med. Assoc. 2007, 298, 299–308.
  17. Norata, G.D.; Grigore, L.; Raselli, S.; Redaelli, L.; Hamsten, A.; Maggi, F.; Eriksson, P.; Catapano, A.L. Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: Molecular mechanisms and gene expression studies. Atherosclerosis 2007, 193, 321–327.
  18. Bernelot Moens, S.J.; Verweij, S.L.; Schnitzler, J.G.; Stiekema, L.C.A.; Bos, M.; Langsted, A.; Kuijk, C.; Bekkering, S.; Voermans, C.; Verberne, H.J.; et al. Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans. Arterioscler. Thromb. Vasc. Biol. 2017, 37, 969–975.
  19. Norata, G.D.; Grigore, L.; Raselli, S.; Seccomandi, P.M.; Hamsten, A.; Maggi, F.M.; Eriksson, P.; Catapano, A.L. Triglyceride-rich lipoproteins from hypertriglyceridemic subjects induce a pro-inflammatory response in the endothelium: Molecular mechanisms and gene expression studies. J. Mol. Cell. Cardiol. 2006, 40, 484–494.
  20. Berry, S.E.; Valdes, A.M.; Drew, D.A.; Asnicar, F.; Mazidi, M.; Wolf, J.; Capdevila, J.; Hadjigeorgiou, G.; Davies, R.; Al Khatib, H.; et al. Human postprandial responses to food and potential for precision nutrition. Nat. Med. 2020, 26, 964–973.
  21. Zhang, D.; Chen, G.; Manwani, D.; Mortha, A.; Xu, C.; Faith, J.J.; Burk, R.D.; Kunisaki, Y.; Jang, J.-E.; Scheiermann, C.; et al. Neutrophil ageing is regulated by the microbiome. Nature 2015, 525, 528–532.
  22. Uehara, K.; Takahashi, T.; Fujii, H.; Shimizu, H.; Omori, E.; Matsumi, M.; Yokoyama, M.; Morita, K.; Akagi, R.; Sassa, S. The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury. Crit. Care Med. 2005, 33, 381–390.
  23. Ren, W.-K.; Yin, J.; Zhu, X.-P.; Liu, G.; Li, N.-Z.; Peng, Y.-Y.; Yin, Y.-Y. Glutamine on Intestinal Inflammation: A Mechanistic Perspective. Eur. J. Inflamm. 2013, 11, 315–326.
  24. Ren, W.; Yin, J.; Wu, M.; Liu, G.; Yang, G.; Xion, Y.; Su, D.; Wu, L.; Li, T.; Chen, S.; et al. Serum Amino Acids Profile and the Beneficial Effects of L-Arginine or L-Glutamine Supplementation in Dextran Sulfate Sodium Colitis. PLoS ONE 2014, 9, e88335.
  25. Wang, W.; Wu, Z.; Lin, G.; Hu, S.; Wang, B.; Dai, Z.; Wu, G. Glycine Stimulates Protein Synthesis and Inhibits Oxidative Stress in Pig Small Intestinal Epithelial Cells. J. Nutr. 2014, 144, 1540–1548.
  26. Wang, T.Y.; Liu, M.; Portincasa, P.; Wang, D.Q.-H. New insights into the molecular mechanism of intestinal fatty acid absorption. Eur. J. Clin. Investig. 2013, 43, 1203–1233.
  27. Beilstein, F.; Carrière, V.; Leturque, A.; Demignot, S. Characteristics and functions of lipid droplets and associated proteins in enterocytes. Exp. Cell Res. 2016, 340, 172–179.
  28. Foster-Powell, K.; Holt, S.H.; Brand-Miller, J.C. International table of glycemic index and glycemic load values: 2002. Am. J. Clin. Nutr. 2002, 76, 5–56.
  29. Cleophas, M.C.P.; Ratter, J.M.; Bekkering, S.; Quintin, J.; Schraa, K.; Stroes, E.S.; Netea, M.G.; Joosten, L.A.B. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci. Rep. 2019, 9, 775.
  30. Du, Y.; Li, X.; Su, C.; Xi, M.; Zhang, X.; Jiang, Z.; Wang, L.; Hong, B. Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice. Br. J. Pharmacol. 2020, 177, 1754–1772.
  31. Baragetti, A.; Severgnini, M.; Olmastroni, E.; Dioguardi, C.C.; Mattavelli, E.; Angius, A.; Rotta, L.; Cibella, J.; Caredda, G.; Consolandi, C.; et al. Gut microbiota functional dysbiosis relates to individual diet in subclinical carotid atherosclerosis. Nutrients 2021, 13, 304.
  32. Bartolomaeus, H.; Balogh, A.; Yakoub, M.; Homann, S.; Markó, L.; Höges, S.; Tsvetkov, D.; Krannich, A.; Wundersitz, S.; Avery, E.G.; et al. Short-Chain Fatty Acid Propionate Protects from Hypertensive Cardiovascular Damage. Circulation 2019, 139, 1407–1421.
  33. Wright, A.T. Gut commensals make choline too. Nat. Microbiol. 2019, 4, 4–5.
  34. Koeth, R.A.; Lam-Galvez, B.R.; Kirsop, J.; Wang, Z.; Levison, B.S.; Gu, X.; Copeland, M.F.; Bartlett, D.; Cody, D.B.; Dai, H.J.; et al. L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J. Clin. Investig. 2019, 129, 373–387.
  35. Caesar, R.; Reigstad, C.S.; Bäckhed, H.K.; Reinhardt, C.; Ketonen, M.; Lundén, G.Ö.; Cani, P.D.; Bäckhed, F. Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice. Gut 2012, 61, 1701–1707.
  36. d’Hennezel, E.; Abubucker, S.; Murphy, L.O.; Cullen, T.W. Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling. mSystems 2017, 2, e00046-17.
  37. Carnevale, R.; Sciarretta, S.; Valenti, V.; di Nonno, F.; Calvieri, C.; Nocella, C.; Frati, G.; Forte, M.; d’Amati, G.; Pignataro, M.G.; et al. Low-grade endotoxaemia enhances artery thrombus growth via toll-like receptor 4: Implication for myocardial infarction. Eur. Heart J. 2020, 41, 3156–3165.
  38. Schönfeld, P.; Wojtczak, L. Short- and medium-chain fatty acids in energy metabolism: The cellular perspective. J. Lipid Res. 2016, 57, 943–954.
  39. Randolph, G.J.; Miller, N.E. Lymphatic transport of high-density lipoproteins and chylomicrons. J. Clin. Investig. 2014, 124, 929–935.
  40. Bonnardel, J.; T’Jonck, W.; Gaublomme, D.; Browaeys, R.; Scott, C.L.; Martens, L.; Vanneste, B.; De Prijck, S.; Nedospasov, S.A.; Kremer, A.; et al. Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche. Immunity 2019, 51, 638–654.
  41. Han, Y.-H.; Onufer, E.J.; Huang, L.-H.; Sprung, R.W.; Davidson, W.S.; Czepielewski, R.S.; Wohltmann, M.; Sorci-Thomas, M.G.; Warner, B.W.; Randolph, G.J. Enterically derived high-density lipoprotein restrains liver injury through the portal vein. Science 2021, 373, eabe6729.
  42. Norata, G.D.; Catapano, A.L. Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. Vasc. Health Risk Manag. 2005, 1, 119–129.
  43. Da Silva, M.S.; Julien, P.; Pérusse, L.; Vohl, M.C.; Rudkowska, I. Natural Rumen-Derived trans Fatty Acids Are Associated with Metabolic Markers of Cardiac Health. Lipids 2015, 50, 873–882.
  44. Chandra, A.; Lyngbakken, M.N.; Eide, I.A.; Røsjø, H.; Vigen, T.; Ihle-Hansen, H.; Orstad, E.B.; Rønning, O.M.; Berge, T.; Schmidt, E.B.; et al. Plasma trans fatty acid levels, cardiovascular risk factors and lifestyle: Results from the Akershus cardiac examination 1950 study. Nutrients 2020, 12, 1419.
  45. Lopez-Garcia, E.; Schulze, M.B.; Manson, J.A.E.; Meigs, J.B.; Albert, C.M.; Rifai, N.; Willett, W.C.; Hu, F.B. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J. Nutr. 2005, 135, 562–566.
  46. Wang, D.D.; Li, Y.; Chiuve, S.E.; Stampfer, M.J.; Manson, J.A.E.; Rimm, E.B.; Willett, W.C.; Hu, F.B. Association of specific dietary fats with total and cause-specific mortality. JAMA Intern. Med. 2016, 176, 1134–1145.
  47. Livingstone, K.M.; Givens, D.I.; Cockcroft, J.R.; Pickering, J.E.; Lovegrove, J.A. Is fatty acid intake a predictor of arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study. Nutr. Metab. Cardiovasc. Dis. 2013, 23, 1079–1085.
  48. Li, Y.; Hruby, A.; Bernstein, A.M.; Ley, S.H.; Wang, D.D.; Chiuve, S.E.; Sampson, L.; Rexrode, K.M.; Rimm, E.B.; Willett, W.C.; et al. Saturated Fats Compared with Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease A Prospective Cohort Study. J. Am. Coll. Cardiol. 2015, 66, 1538–1548.
  49. Nielsen, B.M.; Nielsen, M.M.; Jakobsen, M.U.; Nielsen, C.J.; Holst, C.; Larsen, T.M.; Bendsen, N.T.; Bysted, A.; Leth, T.; Hougaard, D.M.; et al. A cross-sectional study on trans-fatty acids and risk markers of CHD among middle-aged men representing a broad range of BMI. Br. J. Nutr. 2011, 106, 1245–1252.
  50. Oh, K.; Hu, F.B.; Manson, J.E.; Stampfer, M.J.; Willett, W.C. Dietary fat intake and risk of coronary heart disease in women: 20 Years of follow-up of the nurses’ health study. Am. J. Epidemiol. 2005, 161, 672–679.
  51. Sohn, C.; Kim, J.; Bae, W. The framingham risk score, diet, and inflammatory markers in Korean men with metabolic syndrome. Nutr. Res. Pract. 2012, 6, 246–253.
  52. Khayyatzadeh, S.S.; Kazemi-Bajestani, S.M.R.; Bagherniya, M.; Mehramiz, M.; Tayefi, M.; Ebrahimi, M.; Ferns, G.A.; Safarian, M.; Ghayour-Mobarhan, M. Serum high C reactive protein concentrations are related to the intake of dietary macronutrients and fiber: Findings from a large representative Persian population sample. Clin. Biochem. 2017, 50, 750–755.
  53. Salas-Salvadó, J.; Garcia-Arellano, A.; Estruch, R.; Marquez-Sandoval, F.; Corella, D.; Fiol, M.; Gómez-Gracia, E.; Viñoles, E.; Arós, F.; Herrera, C.; et al. Components of the mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur. J. Clin. Nutr. 2008, 62, 651–659.
  54. Guasch-Ferré, M.; Liu, G.; Li, Y.; Sampson, L.; Manson, J.A.E.; Salas-Salvadó, J.; Martínez-González, M.A.; Stampfer, M.J.; Willett, W.C.; Sun, Q.; et al. Olive Oil Consumption and Cardiovascular Risk in U.S. Adults. J. Am. Coll. Cardiol. 2020, 75, 1729–1739.
  55. Guasch-Ferré, M.; Zong, G.; Willett, W.C.; Zock, P.L.; Wanders, A.J.; Hu, F.B.; Sun, Q. Associations of Monounsaturated Fatty Acids From Plant and Animal Sources With Total and Cause-Specific Mortality in Two US Prospective Cohort Studies. Circ. Res. 2019, 124, 1266–1275.
  56. Imran, T.F.; Kim, E.; Buring, J.E.; Lee, I.M.; Gaziano, J.M.; Djousse, L. Nut consumption, risk of cardiovascular mortality, and potential mediating mechanisms: The Women’s Health Study. J. Clin. Lipidol. 2021, 15, 266–274.
  57. Garcia-Arellano, A.; Ramallal, R.; Ruiz-Canela, M.; Salas-Salvadó, J.; Corella, D.; Shivappa, N.; Schröder, H.; Hébert, J.R.; Ros, E.; Gómez-Garcia, E.; et al. Dietary inflammatory index and incidence of cardiovascular disease in the PREDIMED study. Nutrients 2015, 7, 4124–4138.
  58. De Souza, R.J.; Dehghan, M.; Mente, A.; Bangdiwala, S.I.; Ahmed, S.H.; Alhabib, K.F.; Altuntas, Y.; Basiak-Rasała, A.; Dagenais, G.R.; Diaz, R.; et al. Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: Analysis from the Prospective Urban and Rural Epidemiology (PURE) study. Am. J. Clin. Nutr. 2020, 112, 208–219.
  59. Lopez-Garcia, E.; Schulze, M.B.; Manson, J.A.E.; Meigs, J.B.; Albert, C.M.; Rifai, N.; Willett, W.C.; Hu, F.B. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J. Nutr. 2004, 134, 1806–1811.
  60. Pischon, T.; Hankinson, S.E.; Hotamisligil, G.S.; Rifai, N.; Willett, W.C.; Rimm, E.B. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 2003, 108, 155–160.
  61. Ninomiya, T.; Nagata, M.; Hata, J.; Hirakawa, Y.; Ozawa, M.; Yoshida, D.; Ohara, T.; Kishimoto, H.; Mukai, N.; Fukuhara, M.; et al. Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: The Hisayama Study. Atherosclerosis 2013, 231, 261–267.
  62. Madsen, T.; Skou, H.A.; Hansen, V.E.; Fog, L.; Christensen, J.H.; Toft, E.; Schmidt, E.B. C-Reactive Protein, Dietary n-3 Fatty Acid, and the Extent of Coronary Artery Disease. Am. J. Cardiol. 2001, 88, 1139–1142.
  63. Manger, M.S.; Strand, E.; Ebbing, M.; Seifert, R.; Refsum, H.; Nordrehaug, J.E.; Nilsen, D.W.; Drevon, C.A.; Tell, G.S.; Bleie, Ø.; et al. Dietary intake of n-3 long-chain polyunsaturated fatty acids and coronary events in Norwegian patients with coronary artery disease. Am. J. Clin. Nutr. 2010, 92, 244–251.
  64. Mozaffarian, D.; Ascherio, A.; Hu, F.B.; Stampfer, M.J.; Willett, W.C.; Siscovick, D.S.; Rimm, E.B. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation 2005, 111, 157–164.
  65. Bergendal, E. Dietary Fat and Cholesterol and Risk of Cardiovascular Disease in Older Adults: The Health ABC Study. Bone 2008, 23, 1–7.
  66. Bagherniya, M.; Khayyatzadeh, S.S.; Bakavoli, A.R.H.; Ferns, G.A.; Ebrahimi, M.; Safarian, M.; Nematy, M.; Ghayour-Mobarhan, M. Serum high-sensitive C-reactive protein is associated with dietary intakes in diabetic patients with and without hypertension: A cross-sectional study. Ann. Clin. Biochem. 2018, 55, 422–429.
  67. Virtanen, J.K.; Mursu, J.; Tuomainen, T.P.; Virtanen, H.E.K.; Voutilainen, S. Egg consumption and risk of incident type 2 diabetes in men: The kuopio ischaemic heart disease risk factor study. Am. J. Clin. Nutr. 2015, 101, 1088–1096.
  68. Abdollahi, A.M.; Virtanen, H.E.K.; Voutilainen, S.; Kurl, S.; Tuomainen, T.P.; Salonen, J.T.; Virtanen, J.K. Egg consumption, cholesterol intake, and risk of incident stroke in men: The Kuopio Ischaemic Heart Disease Risk Factor Study. Am. J. Clin. Nutr. 2019, 110, 169–176.
  69. Hu, F.B.; Stampfer, M.J.; Rimm, E.B.; Manson, J.A.E.; Ascherio, A.; Colditz, G.A.; Rosner, B.A.; Spiegelman, D.; Speizer, F.E.; Sacks, F.M.; et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. J. Am. Med. Assoc. 1999, 281, 1387–1394.
  70. Baer, D.J.; Judd, J.T.; Clevidence, B.A.; Tracy, R.P. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: A randomized crossover study. Am. J. Clin. Nutr. 2004, 79, 969–973.
  71. Gebauer, S.K.; Dionisi, F.; Krauss, R.M.; Baer, D.J. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: A double-blind, randomized. Am. J. Clin. Nutr. 2015, 102, 1339–1346.
  72. Wang, Z.; Klipfell, E.; Bennett, B.J.; Koeth, R.; Levison, B.S.; Dugar, B.; Feldstein, A.E.; Britt, E.B.; Fu, X.; Chung, Y.M.; et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011, 472, 57–65.
  73. Kien, C.L.; Bunn, J.Y.; Fukagawa, N.K.; Anathy, V.; Matthews, D.E.; Crain, K.I.; Ebenstein, D.B.; Tarleton, E.K.; Pratley, R.E.; Poynter, M.E. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J. Nutr. Biochem. 2015, 26, 1599–1606.
  74. Nicholls, S.J.; Lundman, P.; Harmer, J.A.; Ons, B.S.C.H.; Cutri, B.; Ons, B.M.E.D.S.C.H.; Griffiths, K.A.; Rye, K.; Barter, P.J.; Celermajer, D.S. Consumption of Saturated Fat Impairs the Anti-Inflammatory Properties of High-Density Lipoproteins and Endothelial Function. J. Am. Coll. Cardiol. 2006, 48, 715–720.
  75. Zhao, G.; Etherton, T.D.; Martin, K.R.; West, S.G.; Gillies, P.J.; Kris-Etherton, P.M. Dietary α-Linolenic Acid Reduces Inflammatory and Lipid Cardiovascular Risk Factors in Hypercholesterolemic Men and Women. J. Nutr. 2004, 134, 2991–2997.
  76. Brassard, D.; Tessier-Grenier, M.; Allaire, J.; Rajendiran, E.; She, Y.; Ramprasath, V.; Gigleux, I.; Talbot, D.; Levy, E.; Tremblay, A.; et al. Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: A randomized controlled trial. Am. J. Clin. Nutr. 2017, 105, 800–809.
  77. Teng, K.; Faun, L.; Ratna, S.; Nesaretnam, K.; Sanders, T.A.B. Effects of exchanging carbohydrate or monounsaturated fat with saturated fat on in fl ammatory and thrombogenic responses in subjects with abdominal obesity: A randomized controlled trial. Clin. Nutr. 2017, 36, 1250–1258.
  78. Vafeiadou, K.; Weech, M.; Altowaijri, H.; Todd, S.; Yaqoob, P.; Jackson, K.G.; Lovegrove, J.A. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: Results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS). Am. J. Clin. Nutr. 2015, 102, 40–48.
  79. Voon, P.T.; Ng, T.K.W.; Lee, V.K.M.; Nesaretnam, K. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. Am. J. Clin. Nutr. 2012, 95, 780.
  80. Faintuch, J.; Horie, L.M.; Barbeiro, H.V.; Barbeiro, D.F.; Soriano, F.G.; Ishida, R.K.; Cecconello, I. Systemic inflammation in morbidly obese subjects: Response to oral supplementation with alpha-linolenic acid. Obes. Surg. 2007, 17, 341–347.
  81. Abdelhamid, A.S.; Brown, T.J.; Brainard, J.S.; Biswas, P.; Thorpe, G.C.; Moore, H.J.; Deane, K.H.O.; Summerbell, C.D.; Worthington, H.V.; Song, F.; et al. Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 2020.
  82. Rallidis, L.S.; Paschos, G.; Liakos, G.K.; Velissaridou, A.H.; Anastasiadis, G.; Zampelas, A. Dietary α-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 2003, 167, 237–242.
  83. Bhatt, D.L.; Steg, P.G.; Miller, M.; Brinton, E.A.; Jacobson, T.A.; Ketchum, S.B.; Doyle, R.T.; Juliano, R.A.; Jiao, L.; Granowitz, C.; et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N. Engl. J. Med. 2019, 380, 11–22.
  84. Mitjavila, M.T.; Fandos, M.; Salas-Salvadó, J.; Covas, M.-I.; Borrego, S.; Estruch, R.; Lamuela-Raventós, R.; Corella, D.; Martínez-Gonzalez, M.Á.; Sánchez, J.M.; et al. The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial. Clin. Nutr. 2013, 32, 172–178.
  85. Esposito, K.; Marfella, R.; Ciotola, M.; Di Palo, C.; Giugliano, F.; Giugliano, G.; D’Armiento, M.; D’Andrea, F.; Giugliano, D. Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome. JAMA 2004, 292, 1440.
  86. Davis, C.R.; Hodgson, J.M.; Woodman, R.; Bryan, J.; Wilson, C.; Murphy, K.J. A Mediterranean diet lowers blood pressure and improves endothelial function: Results from the MedLey randomized intervention trial. Am. J. Clin. Nutr. 2017, 105, 1305–1313.
  87. Weinberg, R.L.; Brook, R.D.; Rubenfire, M.; Eagle, K.A. Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids: JACC Focus Seminar. J. Am. Coll. Cardiol. 2021, 77, 593–608.
  88. Storniolo, C.E.; Casillas, R.; Bulló, M.; Castañer, O.; Ros, E.; Sáez, G.T.; Toledo, E.; Estruch, R.; Ruiz-Gutiérrez, V.; Fitó, M.; et al. A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women. Eur. J. Nutr. 2017, 56, 89–97.
  89. Lambert, C.; Cubedo, J.; Padró, T.; Sánchez-Hernández, J.; Antonijoan, R.; Perez, A.; Badimon, L. Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study. Nutrients 2017, 9, 599.
  90. Kirkhus, B.; Lamglait, A.; Eilertsen, K.; Falch, E.; Haider, T.; Vik, H.; Hoem, N.; Hagve, T.; Basu, S.; Olsen, E.; et al. Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects. Br. J. Nutr. 2012, 107, 1339–1349.
  91. Krantz, M.J.; Havranek, E.P.; Pereira, R.I.; Beaty, B.; Mehler, P.S.; Long, C.S. Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: A randomized pilot study. J. Negat. Results Biomed. 2017, 14, 12–17.
  92. Blesso, C.N.; Andersen, C.J.; Barona, J.; Volk, B.; Volek, J.S.; Fernandez, M.L. Effects of carbohydrate restriction and dietary cholesterol provided by eggs on clinical risk factors in metabolic syndrome. J. Clin. Lipidol. 2013, 7, 463–471.
  93. Morgantini, C.; Trifirò, S.; Tricò, D.; Meriwether, D.; Baldi, S.; Mengozzi, A.; Reddy, S.T.; Natali, A. A short-term increase in dietary cholesterol and fat intake affects high-density lipoprotein composition in healthy subjects. Nutr. Metab. Cardiovasc. Dis. 2018, 28, 575–581.
  94. Tricò, D.; Trifirò, S.; Mengozzi, A.; Morgantini, C.; Baldi, S.; Mari, A.; Natali, A. Reducing cholesterol and fat intake improves glucose tolerance by enhancing B cell function in nondiabetic subjects. J. Clin. Endocrinol. Metab. 2018, 103, 622–631.
  95. Blesso, C.N.; Andersen, C.J.; Barona, J.; Volek, J.S.; Luz, M. Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome. Metabolism 2013, 62, 400–410.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback