Thursday, 30 April 2015

The Saturated Fat Debate




Recently as part of a nutritional science module I was given several options of essay subjects, and one of them really jumped out at me.
1)        Nutrition science continues to evolve and we should always challenge the accepted view when new evidence emerges. Discuss this statement, using examples of controversial areas within the subject area of public health nutrition.

Immediately I thought about saturated fat and heart disease.  I said to myself “Finally this is the motivation you need to actually go out and do a ton of reading on the subject to get a full understanding”.  There is loads of books, articles and media posts going round addressing this subject.  What I’m hoping to do with this article is present an objective view of the scientific evidence behind saturated fat and heart disease, and generally shed some more light on fairly complex debate.  So here it is a kind of adaption of the essay I wrote for this module.
I think there is a couple of things I should explain before delving into the article.


LDL (low density lipoprotein) Cholesterol – often referred to as “bad” cholesterol.
HDL (high density lipoprotein) Cholesterol – often referred to as “good” cholesterol.  HDL cholesterol scavenges and removes LDL cholesterol


Relative Risk (RR) - measures the magnitude of an association between an exposed and non-exposed group. It describes the likelihood of developing disease in an exposed group compared to a non-exposed group.
n-3 PUFA – Omega 3 Fats
Foods that are high in saturated fat include....
Red meat
Processed Meat
Coconut
Butter
Cheese
Cream
Chocolate
Animal Fats


Nutritional science is constantly developing as more research is conducted and analyzed.  This requires governing bodies and health advisory committees to adapt when new evidence presents itself.  Saturated fat (SF) has been a focus of public health, as part of nutritional strategies to prevent cardiovascular disease (CVD).  The current guidelines in UK are that SF should contribute no more than 11% to total energy, Current intakes are 12.6%.  It is commonly accepted that SF raises plasma LDL cholesterol, a common risk factor for CVD.  Recently clinical and epidemiological research has been published that appears to dispel the link between SF and CVD.    You may have seen these studies portrayed in media, none more prominent than the headline “Eat Butter” on the front of the Time magazine accompanied by this image showing the apparent change in stance of the scientific community.
Undoubtedly this contradictory message leads to confusion.  I’ve spent a bit of time studying nutrition and the headlines perplexed me, I was thinking how could everything we have been told about saturated fat be untrue.  I think for the sake of the general public just looking to lead a healthy happy life we need to re-evaluate the evidence regarding SF and CVD so a clear evidence based public health approach can be made.
How does Saturated Fat potentially increase risk of CVD?
A diet high in SF reduces esterification of cholesterol and leads to higher concentrations of non-esterified cholesterol.  In response to this, hepatic concentration of LDL receptor mRNA is reduced, consequently LDL receptor activity is reduced leading to raised plasma LDL.  In the development of CVD LDL particles are oxidized within the arterial matrix.  Oxidised LDL leaks into, and accumulates in the sub endothelial space.  Macrophages preferentially take up the oxidised LDL forming foam cells.  Foam cells deposit accumulated oxidised lipids between the endothelium and the arterial smooth muscle, causing stenosis.  This can lead to both ischemic heart disease and cerebrovascular accident.   Imagine LDL particles as drunk drivers there is a greater risk these guys are going to crash into the side of the arteries and cause a massive tail back.  HDL essentially acts as the police or the AA cleaning up after these inconsiderate atherogenic little buggers. 


Contradictory Evidence
Before I go into the contradictory evidence its important to outline why we need saturated fat and cholesterol, what positive bodily processes are they required for?  saturated fats are structural components of sphingolipids and ceramides, which are important components of cell membranes, skin and myelin.  Myelin is particularly interesting in my opinion, it acts as an insulator around the axis of a neuron.  This is why the use of statins ha been associated with higher risk of dementia.  There is lots of other potential benefits to consuming adequate saturated fat including butyric acid which has been linked to protection from cancer and production of caprylic acid, which acts an antiviral agent.
Two large meta-analyses have found evidence that SF intake is not linked to CVD incidence or mortality.   An analysis of prospective cohort studies, including 347,747 participants with a mean follow up of 14.3 years, found that SF intake was not associated with an increased risk of CVD (RR 1.00).  A systematic review and meta-analysis including data from prospective cohorts, observational and randomised control trails, concluded that there currently was not enough evidence to support saturated and polyunsaturated fat (PUFA) guidelines in relation to coronary heart disease (CHD). The study included data from 659,298 participants.  In the prospective cohort data, when the top and bottom thirds of dietary intake were compared CHD RR was 1.02 for SF, 1.00 for monounsaturated fat (MUFA), 0.87 for PUFA, 0.98 for Omega six fat and 1.16 for trans fatty acids.  Furthermore in the studies that measured fatty acid bio markers SF was associated with a RR of 1.06.  Both of these papers relay heavily on prospective epidemiological data.  These require dietary assessment methods where under and over reporting of food intake is common, and they do not account for variability in diet over time. 


A review into the effect SF has on blood lipids from epidemiological, animal and human studies, pointed out the inconsistencies in blood lipid data.  Some trials reporting negative effects and others reporting either neutral or positive effects related to SF intake.  Furthermore various biomarkers have been used to assess CVD risk including total LDL, total cholesterol to HDL ratio and LDL particle size, creating more inconsistency.  The authors proposed that the negative effect of SF on blood lipids was related to a lack of n-3 PUFA, rather than SF alone.  This hypothesis was based on evidence that SF works synergistically with n-3 PUFA, leading to an increase in n-3 PUFA concentration in plasma and liver lipids.  This theory is mostly based on animal studies however some human trials were cited.  A postprandial trial on 59 participants found that when SF was combined with a docosahexaenoic acid rich n-3 PUFA formula, reductions in non-esterified fatty acids occurred compared to SF alone.  Postprandial means the measurements were taken shortly after feeding, so no long term follow up was performed.  The study cannot fully support the hypothesis that SF and n-3 PUFA work synergistically, only that n-3 PUFA may negate some of the negative effects of SF.  More research is required to support this theory and to establish mechanisms and dose response’s.  This study does highlight that previous research on SF has often failed to consider how n-3 PUFA could affect plasma lipid levels.  A large number also did not consider that a particular fat group will never be isolated in the diet.  Using biomarkers as risk factors for CVD is limiting as the effects of diet on CVD risk are mediated by, many pathways with blood lipids being only one.  Although these biomarkers do provide some evidence of increased CVD risk, CVD incidence and mortality are needed to assess the effects of dietary contributors to CVD. 


So biomarkers are fairly good tool for measuring CVD risk, however really we need to be using CVD deaths and incidence as an end point for the most reliability and validity.  Do you see the problem here?  Well if were are doing a randomised control trial we cant ethically give humans something we think might do them harm, so we have to relay on prospective epidemiological studies which follow people and try and figure out trends.  The problems with epidemiological studies are its difficult to accurately assess food or nutrient intakes, and there is so many factors that contribute to CVD risk outside of saturated fat intake its difficult to control for all those factors.  The alternative is animal models which again contribute to the evidence base, but effects do not always translate to free living humans.  You see what I mean when I said it’s a tricky subject.

How do saturated fats compare with other fatty acids and carbohydrate?
When evaluating the recommendations to lower SF intake, it is important to consider the nutrients that replace them.  Current guidelines are to replace SF with MUFA and PUFA. 
To investigate the implications of these dietary changes, eleven cohorts were pooled encompassing 344,696 participants with follow ups varying between four and 10 years.  Five percent total energy from SF was replaced by PUFA, MUFA or carbohydrate.   PUFA was associated with significant reductions in cardiac death and coronary events, RR 0.74 and 0.87 respectively.  Replacement with carbohydrate was associated with a significant increase in coronary events and a non-significant reduction in coronary deaths RR 1.07 and 0.96 respectively.  MUFA replacement was no associated with any change in CVD.


Substituting SF with PUFA has yielded positive results. A systematic review and meta-analysis of RCTs, including data from 13,614 participants, found an overall RR for myocardial infarction or coronary death of 0.81.  Furthermore a meta-regression found that study duration played a significant factor with longer duration studies showing greater benefit.  This is important as most dietary guidelines are encouraged to be followed over a lifespan.  If longer duration translates to greater reductions in risk, the evidence for replacement of SF with PUFA is valuable from a public health perspective. In addition it has been estimated that countries following a westernised diet could expect a mean reduction of 0.06mmol/l in total cholesterol, translating to a 2-3% reduction in CVD incidence by replacing 1% of total energy from SF with 0.5% of PUFA. 
The evidence that replacing SF with MUFA providing a benefit to cardiovascular health is inconclusive.  In human trials MUFA is predominantly derived from meat and dairy products, which are also high in SF, this could explain the lack of protective association.


Evidence that replacement with carbohydrate is mixed.  This could be down to a lack of evidence addressing the specific type of carbohydrate that is being consumed.  In a cohort of 53,644 low glycemic index carbohydrate replacement was associated with an OR of 0.88 for myocardial infarction, this association was not statistically significant.  In the same cohort high glycemic carbohydrate replacement was significantly associated with an OR of 1.33 for myocardial infarction.  This is supported by blood lipid data from a human cohort of 4301, which showed high carbohydrate intake to be associated with significantly higher LDL levels.  Furthermore fibre density was inversely correlated with very small, small and medium LDL particles.  Replacing SF with high glycemic carbohydrate increases total triglycerides and decreases HDL and LDL particle size.  The mechanisms behind this effect are currently not known, however these changes do present a higher risk for CVD.  It is particularly concerning that high glycemic carbohydrate decreases LDL particle size as these are more atherogenic, even in populations at low risk of CVD. Another important factor to consider is the metabolic health of an individual.  Carbohydrate replacement in otherwise healthy individuals is more likely to bring about benefits than in overweight or obese populations, who a have higher prevalence of insulin resistance.


Examples of Refined Carbohydrate Foods

Is it Important to Differentiate between Saturated Fatty Acid Types and Sources?
There is growing evidence that it may be important to differentiate between subclasses of SF.    Lauric (12:0), myristic (14:0) and plamitic (16:0) acids are considered hypercholesterolemic.  Stearic acid (18:0) has a neutral effect on LDL cholesterol, as it is readily de-saturated to oleic acid.  A meta-analysis of 60 clinical trials found that the increase in total cholesterol as a resultant of lauric acid intake, was largely due to an increase in HDL.  This subsequently reduced the total cholesterol to HDL ratio.  Nutritional guidelines in France have increased SF targets to 12% of total energy, with lauric, myristic and palmitic acids, limited to no more than 8% energy.  It is too early to assess if this change in policy has been effective.  One of the difficulties with this type of message is how well it translates to food items as foods contain varying proportions of each SF.  Without appropriate food education or food labelling the guidelines may not translate to the general public.  The information could be useful for food industry reformulation, when a solid fat is needed (e.g. baked goods) stearic could be encouraged to replace other saturated or trans fatty acids.


A major food group that has been focus of debate is dairy products.  There are a number of items in this food group which are high in SF (e.g. cream and cheese).  A meta-analysis of prospective cohorts revealed that high consumption of dairy products, was associated with lower risk of ischaemic heart disease RR 0.79.  There was limited data on specific dairy items.  butter and cheese, two dairy items high in SF, were associated with reductions in vascular events RR 0.93 and 0.90 respectively, neither were statistically significant (Elwood et al., 2010).  Another example of a food item high in SF that has been shown to be beneficial for cardiovascular health is dark chocolate.  Dark chocolate has been shown to the beneficial in observational, mechanistic and RCT studies.  The effect of the SF in these foods may be counterbalanced by the content of protein, calcium, polyphenols and other nutrients. This shows that when considering nutritional guidelines, it is important to consider the entire nutrient matrix of a food item.  In conclusion there is some evidence to support increase in SF recommendations.  This is largely based on prospective cohort studies that are heavily reliant on dietary assessment methods, which can be inaccurate.  In terms of risk biomarkers, the fact that SF raises total and LDL cholesterol is well established by evidence from metabolic studies, but this paradigm may be too simplistic.  Clinical studies will need to consider total cholesterol to HDL ratio and LDL particle size, when assessing CVD risk.  There is still a need for more high quality epidemiological studies, using cardiovascular mortality and events as an end point to support a change in SF guidelines. 


Foods Containing High Levels of each Saturated Fat subtype
Lauric Acid - Pal kernel oil, coconut oil, coconut flesh and butter.
Myristic Acid - Coconut oil, palm kernel oil, coconut flesh, unsalted butter and cream
Palmitic Acid - Palm kernel oil, shortening unsalted butter, lard and beef tallow.
Stearic Acid -  Beef tallow, lard, pork fat, chocolate






Conclusion
There is strong evidence that replacing SF with PUFA reduces CVD risk.  Future studies need to differentiate between n-3 PUFA and n-6 PUFA as they appear to have varying metabolic effects in terms of CVD risk with n-3 PUFA having a more favorable effect.  Nutritional guidelines to consume two portions of oily fish per week encourage this change.  If you want to know more about n-3 PUFA check out my article on Omega 3.


Replacing SF with carbohydrate appears to have a negative effect on cardiovascular outcomes.  Very little evidence exists examining the quality of carbohydrate being introduced, and this has an impact on subsequent CVD risk, and needs to be a focus of future research. 

More food based studies would translate effectively to public health and the general public.  These would also fully encompass the whole nutrient profile of a food group.  This method could be used to assess the effect of MUFA from vegetable and fruit sources, as seen in the Mediterranean diet, on CVD.  If the evidence base does become strong enough to warrant a change in guidelines, the French guidelines would still require reduction in average SF intakes (12.6% to 12%) and would also draw attention to foods high in the more hypercholesterolemic SF.  Food based recommendations would convey a more simplistic message that is more likely to be adopted by the public.


Many other factors need to be considered when evaluating the evidence on a single nutrients contribution to CVD risk.  CVD is a multifactorial condition with many contributing factors.  Furthermore better treatments and changes in associated risk factors will have also played a role in CVD trends.  CVD is a leading cause of premature mortality and morbidity in the UK, so diet advice should aim to reduce this burden however, other prominent issues must be considered in these guidelines e.g osteoporosis, obesity and diabetes. 



References


ASTRUP, A., DYERBERG, J., ELWOOD, P., HERMANSEN, K., HU, F., JAKOBSEN, M., KOK, F., KRAUSS, R., LECERF, J., LEGRAND, P., NESTEL, P., RISERUS, U., SANDERS, T., SINCLAIR, A., STENDER, S., THOLSTRUP, T. AND WILLETT, W., 2011. The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010? American Journal of Clinical Nutrition.  January, vol. 93, no. 4, pp.684-688.


BROWN, J., SHELNESS, G. AND RUDEL, L., 2007. Monounsaturated fatty acids and atherosclerosis: Opposing views from epidemiology and experimental animal models. Current Atherosclerosis Reports.  December, vol. 9, no. 6, pp.494-500.


CHOWDHURY, R., WARNAKULA, S., KUNUTSOR, S., CROWE, F., WARD, H., JOHNSON, L., FRANCO, O., BUTTERWORTH, A., FOROUHI, N., THOMPSON, S., KHAW, K., MOZAFFARIAN, D., DANESH, J. AND DI ANGELANTONIO, E., 2014. Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk. Annals of Internal Medicine.  March, vol. 160, no. 6, pp.398-406.


DIAS, C., GARG, R., WOOD, L. AND GARG, M., 2014. Saturated fat consumption may not be the main cause of increased blood lipid levels. Medical Hypotheses.  December, vol. 82, no. 2, pp.187-195.


ELWOOD, P., PICKERING, J., GIVENS, D. AND GALLACHER, J., 2010. The Consumption of Milk and Dairy Foods and the Incidence of Vascular Disease and Diabetes: An Overview of the Evidence. Lipids,.  April, vol. 45, no. 10, pp.925-939.


FERNANDEZ MLWEST KL., 2005.  Mechanisms by which dietary fatty acids modulate plasma lipids.  The Journal of Nutrition.  September, vol. 135, no. 9, pp2075-2078.


GERBER, P. AND BERNEIS, K., 2012. Regulation of low-density lipoprotein subfractions by carbohydrates. Current Opinion in Clinical Nutrition and Metabolic Care.  July, vol. 15, no. 4, pp.381-385.


HOOGEVEEN, R., GAUBATZ, J., SUN, W., DODGE, R., CROSBY, J., JIANG, J., COUPER, D., VIRANI, S., KATHIRESAN, S., BOERWINKLE, E. AND BALLANTYNE, C., 2014. Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study. Arteriosclerosis, Thrombosis, and Vascular Biology.  February, vol. 34, no. 5, pp.1069-1077.


Hooper, L., Kroon, PA., Rimm, EB., Cohn, JS., Harvey, I., Le Cornu, KA., Ryder, JJ., Hall, WL., Cassidy, A.,  2008.  Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.  American Journal of Clinical Nutrition.  July, vol. 88, no.1, pp 38-50.

LEGRAND P, MORISE A, KALONJI E., 2011.  Update of French nutritional recommendations for fatty acids.  World Review of Nutrition and Dietetics.  August, vol. 102, pp 137-143.

MENSINK, RP., ZOCK, PL., KESTER, AD., KATAN, MB., 2003.  Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials.  American Journal of Clinical Nutrition.  May, vol. 77, no. 5 1146-1155.
 
MOZAFFARIAN, D., MICHA, R. AND WALLACE, S., 2010. Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Med.  March, vol. 7, no. 3, p.e1000252.

NHS., 2013. Ideas to reduce fat in your kids’ diet | Change4Life [online]. [Viewed 13 April. 2015].  Available from: http://www.nhs.uk/change4life/pages/cut-back-on-fat.aspx.


HUNTER, J., ZHANG, J. AND KRIS-ETHERTON, P., 2009. Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. American Journal of Clinical Nutrition.  November, vol. 91, no. 1, pp.46-63.


JAKOBSEN, M., DETHLEFSEN, C., JOENSEN, A., STEGGER, J., TJONNELAND, A., SCHMIDT, E. AND OVERVAD, K., 2010. Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: importance of the glycemic index. American Journal of Clinical Nutrition.  June, vol. 91, no. 6, pp.1764-1768.


JAKOBSEN, M., O'REILLY, E., HEITMANN, B., PEREIRA, M., BALTER, K., FRASER, G., GOLDBOURT, U., HALLMANS, G., KNEKT, P., LIU, S., PIETINEN, P., SPIEGELMAN, D., STEVENS, J., VIRTAMO, J., WILLETT, W. AND ASCHERIO, A., 2009. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. American Journal of Clinical Nutrition.  February, vol. 89, no. 5, pp.1425-1432.


JIANG, X., YANG, Z., CHANDRAKALA, A., PRESSLEY, D. AND PARTHASARATHY, S., 2011. Oxidized Low Density Lipoproteins-Do We Know Enough About Them? Cardiovascular Drugs and Therapy.  October, vol.25, no.5, pp 367-377.


KOLBUS, D., RAMOS, O., BERG, K., PERSSON, J., WIGREN, M., BJARKBACKA, H., FREDRIKSON, G. AND NILSSON, J., 2010. CD8+ T cell activation predominate early immune responses to hypercholesterolemia in Apoe-/- mice. BMC Immunology.  December, vol.11, no.1, pp 11-58.

LOYD-WILLIAMS, F., 2008. Estimating the cardiovascular mortality burden attributable to the European Common Agricultural Policy on dietary saturated fats. Bull World Health Organ.  July, vol. 86, no. 7, pp.535-541.


NETTLETON, J., LEGRAND, P. AND MENSINK, R., 2015. ISSFAL 2014 Debate: It Is Time to Update Saturated Fat Recommendations. Ann Nutr Metab.  January, vol. 66, no. 2-3, pp.104-108.


NEWENS, K., THOMPSON, A., JACKSON, K., WRIGHT, J. AND WILLIAMS, C., 2011. DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity. American Journal of Clinical Nutrition.  August, vol. 94, no. 3, pp.742-748.


SIRI-TARINO, P., SUN, Q., HU, F. AND KRAUSS, R., 2010. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. American Journal of Clinical Nutrition.  March, vol. 91, no. 3, pp.535-546.


SONESTEDT, E., WIRFALT, E., WALLSTRAM, P., GULLBERG, B., DRAKE, I., HLEBOWICZ, J., NORDIN FREDRIKSON, G., HEDBLAD, B., NILSSON, J., KRAUSS, R. AND ORHO-MELANDER, M., 2011. High disaccharide intake associates with atherogenic lipoprotein profile. Br J Nutr.  Ocotber, vol. 107, no. 07, pp.1062-1069.


THE DEPARTMENT OF HEALTH., 2014.  The National Diet and Nutrition Survey.  London.  TSO.





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