One of the more dynamic areas of modern research is nutrition and how it relates to biology. While in the past the more popular medium of discussion was through various diet/weight loss books, now the question of saturated fats and their overall influence on health has shifted to areas of more stringent study. Through most of the modern age of nutrition it has been viewed by the majority that saturated fats were largely negative and should be avoided as much as possible. Even the USDA recommends less than 10% of calories be derived from saturated fats1,2 largely based on the premise that increasing saturated fat consumption increases detrimental health outcomes including cardiovascular heart disease (CHD).3-5 However, there are individuals that believe this recommendation is inappropriate for it has not been clearly demonstrated empirically that increased consumption of saturated fat increases CHD or other negative health outcomes.
In fact some cite that while increasing saturated fat does increase total cholesterol, which is a characteristic for an increased rate of CHD, the rate of increase for high density lipoprotein (HDL) exceeds the rate of increase for low density lipoprotein (LDL), thus increasing the HDL/LDL ratio which is thought to be a more important factor to overall health than total cholesterol.6 Therefore, in the eyes of these individuals increasing saturated fatty acid (SFA) consumption in an equal caloric substitution over other types of nutrients like carbohydrates does not increase CHD risk and may even lower it.7-10 Overall the problem with both positions regarding the health effects of saturated fat is that most analysis fails to appreciate the specificity that addressing such an issue demands.
The crux of the question does involve the level at which one consumes saturated fats, but there are four central questions that govern the importance of that change:
First, different individual SFAs do not have the same biological effects despite similar molecular constructs. For example some epidemiological evidence demonstrates that stearic acid is the most detrimental SFA in terms of increasing the probability of CHD.11 Also despite the difficulty distinguishing between the overall effects of different SFAs palmitic acid is thought to be more detrimental to overall health than lauric acid. Not surprisingly in overall cholesterol raising effects stearic acid is neutral while all other long-chain acids increase both HDL and LDL levels versus low quality carbohydrates.12 There are no definitive conclusions regarding the influence of short and medium-chain SFAs due to a lack of study.
One of the reasons stearic and palmitic acid are so bad is that they can provide a negative feedback on acetyl-CoA carboxylase (ACC), the enzyme responsible for the catalysis of acetyl-CoA to malonyl-CoA which is utilized to increase the size of acyl chains reducing palmitic acid processing.13 In some respects there is little difference between trans-fatty acids and these two SFAs.
One would anticipate that it would be difficult to separate different types of SFAs with respect to what foods an individual consumes due to the combination of various SFAs in foods. However, it is feasible to distinguish certain specific foods that have higher percentages of certain SFAs over others and make broad dietary suggestions about those food items. For example palm oil and coconut oil have very high in palmitic and lauric acid concentrations respectively. Therefore, when studying the difference between SFAs and carbohydrates it is important to track what foods are consumed to ensure objectivity regarding certain SFA specific overload foods.
Second, when changing the amount of consumed SFAs some other molecule will replace those calories, thus it is important to consider the nature of that replacement and its specificity. Of the four issues that will be discussed this issue of substitution is the most studied one. There are a wide variety of elements that can replace saturated fat in a diet: protein, poly-unsaturated fat, mono-unsaturated fat, high glycemic index (low-quality/processed) carbohydrates, low glycemic index (high-quality) carbohydrates, “normal”/unsaturated fat and trans fats. Preliminary studies support the belief that rates of CHD decrease when replacing SFAs with poly-unsaturated fat, mono-unsaturated fat and “normal” fat.3,14,15 CHD rates increase when replacing SFAs with trans fats and refined/processed carbohydrates.3,16 Note that the glycemic index is utilized to measure how quickly blood sugar rise after consuming a given food and uses glucose as a upper level (100).
However, with regards to the carbohydrates since a large number of the carbohydrates that are consumed in modern society are of high glycemic variety if one were to guess it stands to reason that most, if not all, carbohydrate studies involved processed carbohydrates instead of quality carbohydrates. For example some proponents of SFAs like to cite studies that conclude a switch from SFAS to carbohydrates increases CHD probability. However, these studies do not typically differentiate between carbohydrate types. There is a large biological difference between low glycemic and high glycemic carbohydrates; without differentiating between carbohydrates any results born from substituting SFAs with a caloric equivalent amount of carbohydrates are inherently suspect. Think of it this way anyone who concludes that there is no biological and nutritional difference between consuming 150 calories of traditional rolled oats oatmeal versus 150 calories of Twinkie should not have their opinion taken into consideration.
In addition substitution studies must take appropriate caloric equivalency into account. For example if SFAs makes up 300 calories of a person’s daily caloric intake suitable comparison would demand that some percentage of that value be replaced with an equal value of the replacement (carbohydrates, poly unsaturated fat, etc.). It is sometimes difficult to track this equivalency feature if individuals are simply trying to recall what they consume over a given period of time versus keeping a food diary and having nutritionists correct for imbalances. Finally there is almost no information pertaining to replacing SFAs with protein or low glycemic index carbohydrates with regards to influence on CHD rates further limiting the value of substitution studies, an important exclusion that must be corrected for a definitive statement can be made regarding substitution. In the current environment the burden of proof is on those that believe SFAs are neutral or even better for health than processed carbohydrates, thus they need to ensure the quality of these substitution studies if they want to make the above contention.
Third, one of the biggest problems with comparing health effects between consumption of different food elements is a lack of comparison between subject microbiota. In short the microbiota is the concentration and type of bacteria population in an individual’s gastro-intestinal system. Numerous studies have demonstrated that the type of bacteria in an individual’s intestinal system have a significant impact on the ability to process and absorb nutrients.17-21 One of the biggest comparisons in microbiota is between Firmicutes and Bacteroidetes, which generally identifies obese individuals and non-obese individuals where Firmicutes is at larger concentrations in the obese and Bacteroidetes is at larger concentrations in the non-obese, usually with a 100%+ change.17,18 Note that this relationship is obviously not perfect, but is generally a good rule of thumb.
Evidence has shown that prolonged high SFAs feeding induced inflammation, impaired barrier function and changed microbiota profiles.22 The change in profiles lead to increased concentrations of Firmicutes and Oscillibacter and reduced concentrations of Bacteroidetes and Lactobacillus, thus high SFA feedings change the microbiota to one more seen in obese individuals. Clearly obesity is known for numerous detrimental health conditions, thus possessing a similar microbiota can be rationally viewed as a detrimental outcome versus a beneficial one.
Gut microbiota is important relative to carbohydrate processing as well in the rates and what types of carbohydrates are digestible.23,24 Fermentation occurring in the gut also leads to an increase in GLP-1 synthesis and insulin metabolism, thus rats fed a high fiber diet have higher plasma GLP-1, insulin and c-peptide levels after an oral glucose load.17 Various bacteria breakdown carbohydrates in fermentation reactions producing short chain fatty acids (SCFAs) like acetate, propionate and butyrate.25 Butyrate largely provides energy for colonic epithelia, propionate is taken up by the liver and is a precursor for gluconeogenesis, protein synthesis and liponeogenesis26,27 and acetate is metabolized by peripheral tissues and used as a substrate for cholesterol synthesis.28
The ratio of which SCFAs are produced is largely dependent on the ratio of bacteria in the gut. Evidence suggests that Firmicutes is able to produce about 25% more SCFAs than Bacteroidetes.19,20 Firmicutes appears to produce more butyrate and propionate with Bacteroidetes producing more acetate.29 There is question whether or not higher amounts of SCFAs are linked to obesity, but the evidence favors the affirmative: that increased SCFAs increase obesity probability.18,21,30 Also Firmicutes may increase the rate of malonyl-CoA activation over Bacteroidetes, which reduces the rate of carnitine palmitoyl transferase-1 reducing the amount of mitochondrial fatty acid oxidation.31 Overall while there is still a lot of information that needs to be deduced from the relationship between microbiota and health in general, especially obesity, the exclusion of any relationship in substitution studies is inappropriate.
Fourth, with regards to carbohydrate substitution, physical and aerobic conditioning of the research subject must be taken into consideration. Consistent exercise results in the increased direct and indirect consumption of carbohydrates as an energy source. Indirect consumption occurs through the increased production of specific enzymes, which favor the conversion of certain carbohydrates to glycogen versus SFAs like stearic or palmitic acid. Basically if one is substituting carbohydrates for SFAs in overweight and/or inactive research subjects the biological reduction of SFA consumption is heavily handicapped because the substituted carbohydrates are less likely to be used as short-term energy, but instead are converted to SFAs for long term energy storage.
One of the important elements when distinguishing between biological effects of SFAs and carbohydrates is the synthesis and consumption of glycogen. Glycogen is a multi-branched polysaccharide consisting of various glucose derivative molecules bound together and is used for long-term energy storage in a more compact form over triglycerides.
Glycogen is principally isolated within muscles, the liver and red blood cells32,33 and its rate of storage is dependant on physical training, basal metabolic rate and eating habits. Storage begins when blood glucose levels rise and insulin concentrations increase stimulating the action of hepatocytes leading to glycogen synthesis. As long as glucose and insulin remain in high relative concentrations glycogen synthesis continues. In periods of low glucose the pancreas secretes glucagons which catalyzes glycogenolysis.
Not surprisingly glycogen synthesis is exogonic, where UTP reacting with glucose-1-phosphate to drive the formation of UDP-glucose that eventually combine to lengthen glycogen through catalyzation by glycogen synthase forming from a base created by glycogenin.33 Glycogen consumption is endergonic where sections are cleaved by glycogen phosphorylase to produce glucose-1-phosphate monomers, which are later converted to glucose-6-phosphate by phosphoglucomutase. Glucose-6-phosphate produced from glycogen can enter the glycolysis pathway, the pentose phosphate pathway or be dephosphorylated back to glucose.33
A history of exercise, especially endurance training, enhances lipid and carbohydrate oxidation and decrease SNS activity during present time exercising in part due to increased muscle glycogenolysis and increased recruitment of skeletal muscle.34-38 Increasing exercise intensity increases the level of energy demand from the muscles and brain resulting in a faster crossover from lipids to carbohydrates as a source of energy. While some believe that there are special exercise-dietary regimens to enhance muscle glycogen storage/consumption rates when appropriate, there is no doubt that individuals who exercise consistently have higher rates of glycogen conversion of glucose and other sugars versus rates of glucose conversion to SFAs opposed to the rates found in overweight or obese individuals.34,39,40
One of the advantages of this difference is in the short period of time after exercise (24 hrs) is that rate of glycogen synthesis is indiscriminate the type of carbohydrate, be it simple or complex.40 Note that there is still an insulin concentration rise for simple carbohydrates over complex, but while the increase for complex is smaller the duration is longer.40 The fate of consumed carbohydrates is also influenced by the time between consumption and exercise.41 Therefore, individuals that are “in shape” are more likely to burn off consumed carbohydrates versus storing them as either glycogen or SFAs. Again comparison studies between SFAs and substitutions, especially carbohydrates, tend to exclude the influence of exercise.
Another side issue that must be considered when making comparison studies between SFAs and substitutes is the concentration of epinephrine due to its lipolytic, glycogenolytic and insulin-suppressive effects.42 Past training through exercise seems to reduce epinephrine concentrations in both at rest and during present exercise.42,43 Therefore, measurement of epinephrine needs to be conducted to act as a control point to make more accurate comparisons in substitution studies.
Overall there are clearly scientific and accuracy concerns regarding claims made by individuals who believe that SFAs are no more harmful to CHD rates than carbohydrates. Unfortunately such claims are typically made by individuals who are trying to justify a certain nutritional lifestyle versus individuals who actually care about proper nutrition. This is not to say that all forms of carbohydrates are guaranteed to be healthier than SFAs; the problem is that SFAs proponents have not produced evidence to demonstrate this conclusion that satisfies the four above concerns. Therefore, until this evidence is produced it is irresponsible of individuals to suggest that substituting SFAs for carbohydrates produces no detrimental change to CHD rates.
1. Hoenselaar, R. “Saturated fat and cardiovascular disease: The discrepancy between the scientific literature and dietary advice.” Nutrition. 2012. 28:118-123.
2. U.S. Department of Agriculture (USDA) Food Guide or the Dietary Approaches to Stop Hypertension (DASH) Eating Plan. http://www.unco.edu/shc/topics/dietaryguidelines.htm
3. Jakobsen, et Al. “Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.” Am J Clin Nutr. 2009. 89:1425–32.
4. Dayton, S, et Al. “A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis.” Circulation. 1969. 40(suppl 2):1–63.
5. Turpeinen, O, et Al. “Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study.” Int J Epidemiol. 1979. 8:99–118.
6. Prospective Studies Collaboration. “Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.” Lancet. 2007. 370:1829–39.
7. Astrup, A, et Al. “The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?” Am. J. Clin. Nutr. 2011. 93:684-688.
8. Frantz, I Jr, et Al. “Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.” Arteriosclerosis. 1989. 9:129–35.
9. Siri-Tarino, P, et Al. “Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.” Am. J. Clin. Nutr. 2010. 91:535–546.
10. Skeaff, C, and Miller, J. “Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials.” Ann Nutr Metab. 2009. 55:173–201.
11. Hu, F, et Al. “Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women.” Am J Clin Nutr. 1999. 70:1001–8.
12. Hunter, J, Zhang, J, Kris-Etherton, P. “Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review.” Am J Clin Nutr. 2010. 91:46–63
13. Wikipedia - Palmitic acid Entry.
14. Laaksonen, D, et Al. “Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids.” Arch Intern Med. 2005. 165:193–9.
15. Soinio, M, et Al. “Dietary fat predicts coronary heart disease events in subjects with type 2 diabetes.” Diabetes Care. 2003. 26:619–24.
16. Danaei, G, et Al. “The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.” PLoS Med. 2009. 6:e1000058.
17. Cani, P, and Delzenne, N. “The role of the gut microbiota in energy metabolism and metabolic disease.” Current Pharmaceutical Design. 2009. 15:1546-1558.
18. Ley, R, et Al. “Microbial ecology: human gut microbes associated with obesity.” Nature. 2006. 444:1022-3.
19. Schwietz, A, et Al. “Microbiota and SCFA in lean and overweight healthy subjects.” Obesity. 2009. 18:190-195.
20. Bajzer, M, and Seeley, R. “Physiology: obesity and gut flora.” Nature. 2006. 444:1009–1010.
21. Turnbaugh, P, et Al. “An obesity-associated gut microbiome with increased capacity for energy harvest.” Nature. 2006. 444:1027–1031.
22. Lam, Y, et Al. “Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice.” PloS ONE. 2012. 7(3):e34233.
23. Goodlad, R, et Al. “Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations.” Gut. 1987. 28: 171-80.
24. Goodlad, R, et Al. “Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY.” Gut. 1987. 28(Suppl): 221-6.
25. Macfarlane, G, and Gibson, G. “Carbohydrate fermentation, energy transduction and gas metabolism in the human large intestine.” In: Mackie RI, White BA (eds). Gastrointestinal Microbiology. Chapman & Hall: New York, USA, 1997. 269–317.
26. Wolever, T, Spadafora, P, and Eshuis, H. “Interaction between colonic acetate and propionate in humans.” Am J Clin Nutr. 1991. 53:681–687.
27. Vernay, M. “Origin and utilization of volatile fatty acids and lactate in the rabbit: influence of the faecal excretion pattern.” Br J Nutr. 1987. 57:371–381.
28. Wolever, T, et Al. “Effect of rectal infusion of short chain fatty acids in human subjects.” Am J Gastroenterol. 1989. 84:1027–1033.
29. Duncan, S, et Al. “Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces.” Appl Environ Microbiol. 2007. 73:1073–1078.
30. Ley, R, et Al. “Obesity alters gut microbial ecology.” PNAS. 2005. 102:11070–11075.
31 Pyra, K, et Al. “Prebiotic Fiber Increases Hepatic Acetyl CoA Carboxylase Phosphorylation and Suppresses Glucose-Dependent Insulinotropic Polypeptide Secretion More Effectively When Used with metformin in obese rats.” J. Nutr. 2012. 142:213–220.
32. Moses, S, Bashan, N, and Gutman, A. “Glycogen metabolism in the normal red blood cell.” Blood. 1972. 40(6):836–43. PMID 5083874.
33. Miwa, I, and Suzuki, S. “An improved quantitative assay of glycogen in erythrocytes”. Annals of Clinical Biochemistry. 2002. 39(Pt 6): 612–3. doi:10.1258/000456302760413432.
34. Brooks, G, and Mercier, J. “Balance of carbohydrate and lipid utilization during exercise: the" crossover" concept.” Journal of Applied Physiology. 1994. 76(6):2253-2261.
35. Davies, K, Packer, L, and Brooks, G. “Biochemical adaptation of mitochondria, muscle and whole-animal respiration to endurance training.” Arch. Biochem. Biophys. 1981. 209:539-554.
36. Holloszy, J. “Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise.” J. Appl. Physiol. 1990. 68:990-996.
37. Henriksson, J, and Reitman, J. “Time course of changes in human muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity.” Acta Physiol. Stand. 1977. 99:91-97.
38. Kirkwood, S. P., L. Packer, and G. A. Brooks. Effects of endurance training on a mitochondrial reticulum in limb skeletal muscle. Arch. Biochem. Biophys. 255: 80-88, 1987.
39. Sumida, K, and Donovan, C. “Enhanced gluconeogenesis from lactate in perfused livers after endurance training.” J. App. Physiol. 1993. 74:782-787.
40. Costill, D, et Al. “The role of dietary carbohydrates in muscle glycogen resynthesis after strenuous running.” Am. J. Clin. Nutr. 1981. 34:1831-1836.
41. Jeukendrup, A. “High-carbohydrate versus high-fat diets in endurance sports.” Sportmedizin und Sporttraumatologie. 2003. 51(1):17–23.
42. Brooks, G, et Al. “Increased dependence on blood glucose after acclimatization to
4,300 m.” J. Appl. Physiol. 1991. 70:919-927.
43. Deuster, P, et Al. “Hormonal and metabolic responses of untrained, moderately trained, and highly trained men to three exercise intensities.” Metabolism. 1989. 38:141-148.