Factors Promoting Elevated Serum Triglycerides and Fatty Liver

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By James J. Kenney, PhD, FACN

Elevated fasting and postprandial triglyceride (TG) levels are often associated with insulin resistance and are often an early warning sign that someone may be headed toward type 2 diabetes mellitus (DM) and a have a heightened risk of developing more atherosclerosis and a fatty liver. In the USA and increasingly around the world we are seeing more people developing the metabolic syndrome, which frequently is a prelude to the development of type 2 DM and cardiovascular disease (CVD)(1). There is a strong consensus that this growing epidemic of metabolic abnormalities (called the “metabolic syndrome”) is being driven in large part by excessive calorie intake coupled with inactivity and the increase in abdominal fat stores. As weight increases, especially in genetically-prone people, so too does insulin resistance and fasting and postprandial TG levels (2). The Diabetes Primary Prevention Trial clearly demonstrated the efficacy of a healthier diet, even modest weight loss, and regular aerobic exercise in preventing the progression of the metabolic syndrome to type 2 DM (3).

Numerous other metabolic disturbances are often associated with elevated TG levels, including elevated blood pressure (BP), reduced HDL-C and impaired reverse cholesterol transport (RCT), smaller but more numerous LDL-particles (-P), increased inflammatory substances (including CRP), elevated fasting and postprandial blood sugar (BS) levels, increased uric acid levels, and a fatty liver. In the longer term, these metabolic disturbances lead to more atherosclerotic plaques and more unstable plaques as well as beta-cell failure and type 2 DM. The majority of individuals who develop these metabolic disturbances eventually succumb to CVD morbidity and mortality. Aside from exercise and weight loss, what other dietary changes may reduce fat accumulation in the liver and lower serum TG levels?

Does Replacing Carbohydrate with Fat or Protein Calories Reduce TG Levels?

The answer is generally yes if calorie intake, saturated fat, cholesterol, fiber, and other dietary variables are held more or less constant. This is why most nutrition experts now recommend reducing the amount of dietary carbohydrate and replacing some of the carbohydrate with more unsaturated fat and/or protein as a way to even more effectively lower elevated TG levels and perhaps further reduce CVD risk, especially in those who have type 2 DM. Certainly, the evidence from the OmniHeart Trial demonstrated that the partial substitution of carbohydrate with either protein and/or unsaturated fat does lower fasting serum TG levels and other CVD risk factors. It is assumed that the lower TG levels and changes seen in other CVD risk factors would further reduce CVD events compared to the original higher-carbohydrate DASH diet. The OmniHeart’s carbohydrate-rich diet was similar to the original well-recognized DASH diet. The higher-protein OmniHeart diet appeared to be an even healthier alternative for those who wish to consume additional protein. The higher-unsaturated-fat OmniHeart diet was a sort of Mediterranean-style DASH diet. Although the three versions of OmniHeart diets had distinct features in their macro-nutrient profiles, each was designed to follow many of the principles of the original DASH diet, which likely accounts for a portion of the impressive CVD risk factor reduction from baseline in all three diets compared to a more typical American diet. Given the variety of eating patterns in the US population, the OmniHeart diet patterns offers more flexibility in macronutrient intake that should make it easier to eat a heart-healthy diet and reduce CVD risk (4). However, it should be noted that the amount of saturated fat, cholesterol, and fiber were the same on all three versions of the DASH-style diet used in OmniHeart clinical trial. The higher-protein diet did not replace beans, whole grains, and fruits with more lean meat and low-fat dairy and the higher-unsaturated-fat diet did not displace the high-carbohydrate plant foods with more refined oils as those exchanges would have increased the saturated fat and cholesterol content of the OmniHeart diet and reduced the fiber content of the higher-protein diet. Likewise, the saturated fat content would have increased and the fiber content fallen on the OmniHeart higher-unsaturated-fat diet relative to the high-carbohydrate diet. So to keep the saturated fat (and cholesterol) content and fiber content and calorie intake the same on all three versions of the OmniHeart diets, the high-carbohydrate had them eat much larger desserts and more fruit juice on the high-carbohydrate OmniHeart diet compared to the higher protein and unsaturated fat versions of OmniHeart diet. This made it easier to keep the calorie intake (and body weight) the same on all three OmniHeart diets. Therefore, it would be a mistake to conclude that the OmniHeart study suggests people would be better off replacing whole plant foods with more lean meat, low-fat dairy products, and/or more refined oils high in unsaturated fatty acids.

Higher Fat and Animal Protein Intake Not Always Healthy

It has been shown that when people consume foods with an increasing amount of dietary fat, ad libitum energy intake usually increases. In a study conducted by Dr. Lissner and associates, Lissner had women consume diets in which either 15-20%, 30-35%, or 45-50% of the energy was derived from fat. The participants consumed their assigned diets for 2 weeks, and these diets consisted of foods that were similar in appearance and palatability. The difference lay in the amount of high-fat ingredients. Relative to their calorie intake on the medium-fat diet, the subjects spontaneously consumed an 11.3% deficit on the lowest-fat diet and a 15.4% surfeit on the highest-fat diet (p < 0.0001). This resulted in significant changes in body weight (p < 0.001) (5). While reduction in ad libitum energy intake and weight loss would generally be expected to improve insulin sensitivity and lower serum TG levels and other CVD risk factors, the Lissner et. al. study did not examine those variables. Another study conducted at Tufts University by Dr. Lichtenstein and colleagues evaluated the effects of diets with varying levels of fat (36%, 29% , and 15% of calories) on serum TG, apoB, and nonHDL-C levels. The results of this study showed that very-low-fat diets markedly elevated serum TG levels when calorie intake was the same as consumed on the higher fat diets. Dr. Lichtenstein and associates concluded that very low-fat diets (15% of calories) that are very high in carbohydrate “…beneficially affect plasma lipid profiles relative to the baseline (36% of calories) or reduced-fat (29% of calories) diets only when accompanied by weight loss” (6). It should be noted that the Lichtenstein et. al. study showed that even when subjects consumed the higher carbohydrate diet and lost a little weight, their fasting serum TG levels were still significantly higher than on the higher fat diet. However, as shown in Figure 2 of this study, the postprandial TG levels during the day tended to be higher than on the 29% vs the 15% fat diet. And Figure 2 also shows that the nonHDL-C both fasting and postprandially remained a bit lower on average on the 15% vs 29% fat diet.

While displacing dietary carbohydrate with a higher protein intake in the OmniHeart trial lowered some CVD risk factors, it is important to realize that  this was a short-term clinical trial and far too short to measure any significant changes in CVD events. By contrast, the recent long-term follow-up data from the PERIMED trial recently observed that a “Higher total protein intake, expressed as percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46).” They also observed a “…higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively).” The results of the PERIMED data suggest that, over the longer term, a higher protein intake may nearly double the chances of gaining weight and increase the risk of dying from all causes combined by about 60%. This would happen when people consume a greater proportion of their total energy intake from animal protein. So displacing either dietary carbohydrate or unsaturated fat with more animal protein may lower TGs and some other CVD risk factors in the short term, but over many years in the real world, dietary advice to up animal protein intake may well increase the risk of dying. The PERIMED trial concluded that over the longer term a higher consumption of animal protein was associated with a significantly greater risk of dying from all causes combined when the animal protein was substituted for either dietary carbohydrate or fat (7).

Is there a better way to lose excess weight and lower CVD risk factors than simply focusing on the ratio of fat to protein to carbohydrate?

Curtail Consumption of Sugar-Rich Beverages

Reducing the intake of fructose, especially from beverages sweetened with sugar or high fructose corn syrup (and also fruit juices) appears to reduce fat synthesis in the liver. This can help reduce both fasting and postprandial TG levels as well as markedly reducing liver fat accumulation. A study presented by Dr. Jean-Marc Schwarz at The Endocrine Society’s annual meeting this past March 2015 in California examined the impact of replacing calories from sugary drinks and fruit juices with complex carbohydrates (bread, pasta, and vegetables). They fed 40 obese children (median age 13y) a diet in which the total energy intake and macronutrient ratios remained unchanged for just 9 days and yet still found a 20% reduction in liver fat deposits despite no significant reduction in body weight. Dietary fructose has been shown to stimulate fat synthesis in adults (8). CVD risk factors associated with the metabolic syndrome have also been shown to worsen when dietary fructose is increased at the expense of unsaturated fat, and starch (9).

Cut Back on Saturated Fat and Cholesterol-Rich Foods

People with the metabolic syndrome are already at elevated risk of CVD. Consuming more foods rich in saturated fat and cholesterol are known to increase the levels of apoB-containing atherogenic lipoproteins. The increase occurs in both fasting and postprandial levels of LDL-C and remnants of VLDL and chylomicrons that also are known to deliver cholesterol to the artery wall. Red meats and especially processed meats and fatty dairy products elevate both serum TG levels (especially postprandially) and serum nonHDL-C levels. Saturated fatty acids not only raise the levels of atherogenic lipoproteins but also increase levels of CRP and inflammatory cytokines in the blood and promote IR, glucose intolerance, and lead to more CVD and type 2 DM (10).

Alcohol and Omega-3s Fatty Acids

While there is compelling evidence that both a little alcohol (no more than 1-2 drinks) and omega-3s 91-3g/day) may help reduce CVD risk, there is convincing evidence that in larger amounts of alcohol can promote a fatty liver, raise BP and promote CVD. By contrast, modest amounts of omega-3s from fish like salmon, mackerel, and sardines or plant sources like flaxseeds not only help lower elevated serum TG levels and at least some inflammatory cytokines. However, in larger amounts eating even omega-3 rich seafood will likely raise LDL-C levels and may promote atherosclerosis. Even so eating omega-3 rich fish in place of eggs, fatty dairy products and red meats does not appear to increase the risk of type 2 DM as some investigators once suspected. Indeed, the shorter omega-3 (alpha linolenic acid) found in plants may also provide some protection against both type 2 DM and CVD (11).

Bottom Line: The top priority for people with elevated serum TG levels and especially those with the metabolic syndrome and/or type 2 DM should be to reduce excessive body fat stores and keep off those excess pounds. This should ideally be done with regular exercise and by adopting a low calorie dense diet that is high in fiber. It is not by encouraging people to consume more fatty dairy products, eggs, or red and processed meats, because all are high in saturated fat and cholesterol. Replacing most of those types of foods with omega-3-rich seafood and legumes may help reduce serum TGs and inflammation while further reducing IR and CVD risk. This will likely cut CVD risk even if no weight loss can be sustained. It is also important to advise those with elevated TG levels and IR to curtail their intake of sugar-sweetened drinks and foods high in refined grains, as this too will likely help them reduce body fat stores and again will likely slow the progression of type 2 DM and/or CVD even if no weight loss can be sustained.

References:

  1. Astrup A, Dyerburg J, Selleck M, Sender S. Nutrition transition and its relationship to the development of obesity and related chronic diseases. Obes Rev. 2008;9 supple 1:48-52
  2. Olufadi R, Byrne CD. Clinical and laboratory diagnosis of the metabolic syndrome. J Clin Pathol. 2008;61(6):697-706
  3. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, DPP Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002;346:393-403
  4. Swain JF, McCarron PB, Hamilton EF, et. al. Characteristics of the Diet Patterns Tested in the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart): Options for a Heart-Healthy Diet. J Am Diet Assoc. 2008; 108(2): 257–265
  5. Lissner L, Levitsky DA, Strupp BJ, et. al. Dietary fat and the regulation of energy intake in human subjects. Am J Clin Nutr. 1987;46:886-92
  6. Lichtenstein AH, Ausman LM, Carrasco W, et. al. Short-term Consumption of a Low-Fat Diet Beneficially Affects Plasma Lipid Concentrations Only When Accompanied by Weight Loss. Arterioscler Thromb. 1994;14:1751-1760
  7. Hernández-Alonso P, Salas-Salvadó J, Ruiz-Canela M, et. al. High dietary protein intake is associated with an increased body weight and total death risk. Clinical Nutrition. 2015 - DOI: http://dx.doi.org/10.1016/j.clnu.2015.03.016
  8. Parks EJ, Skokan LE, Timlin MT, et. al. Dietary sugars stimulate fatty acid synthesis in adults. J Nutr. 2008;138:1039-46
  9. Kelly GL, Allan G, Azhar S. High dietary fructose induces a hepatic stress response resulting in cholesterol and lipid dysregulation. Endocrinology. 2004;145:548-55
  10. Chait A, Kim F. Saturated Fatty Acids and Inflammation: Who Pays the Toll? Arterioscler Thromb Vasc Bio. 2010; 30: 692-693
  11. Wu JH, Micha R, Imamura F, et.al. Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis Br J Nutr. 2012: 107 Suppl 2:S214-27
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