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Healthy Lifestyle Behaviors and Triglycerides

Miller, Michael MD1; Kris-Etherton, Penny M. PhD, RD2; Stone, Neil MD3

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doi: 10.1097/01.NMD.0000407734.72146.cd

KEY MESSAGES

  • Lifestyle changes are recommended as the primary means to reduce triglyceride (TG) levels in patients with hypertriglyceridemia.
  • TG lowering is facilitated by weight loss, increasing physical activity, reducing simple carbohydrates, increasing dietary fiber, restricting fructose, consuming marine-derived omega-3 fatty acids, and implementing a Mediterranean-style diet.
  • It is not clear if pharmacologic therapy to reduce TGs is effective for the prevention of cardiovascular events; additional evidence from randomized trials is needed.

The recent American Heart Association (AHA) statement on triglycerides (TGs) and cardiovascular disease (CVD)1 focuses on a lifestyle-based approach as the cornerstone of therapy for hypertriglyceridemic states. Healthy lifestyle behaviors, especially following a recommended dietary pattern, achieving a healthy body weight, and participating in regular physical activity, are important in the management of elevated TG levels.

FAT DISTRIBUTION AND TRIGLYCERIDES

Obesity, typically resulting from excess calories and a sedentary lifestyle, contributes significantly to hypertriglyceridemia, especially when fat accumulates in the visceral (i.e., omental) region.2 In contrast, body fat that accumulates in the legs and gluteal region is less likely to be associated with hypertriglyceridemia.3 In fact, an inverse relationship exists between gluteofemoral fat and systemic inflammation.4 The basis for these anatomically divergent responses reflects, in part, decreased blood flow in the gluteal region and reduced activity of hormone-sensitive lipase, the primary enzyme regulating mobilization of free fatty acids from adipose tissue.5 Under normal physiologic conditions, insulin inhibits fat mobilization from adipocytes. However, in insulin-resistant states, this powerful inhibitory effect is compromised and, as a result, free fatty acids are mobilized from adipocytes to the liver where increased secretion of TG-enriched very-LDL (VLDL) particles facilitates hypertriglyceridemia6 (eFigure 1; published online, Supplemental Digital Content 1, see http://links.lww.com/CNI/A1).

In addition to the central role played by visceral fat and insulin-resistant states, the aging process also is associated with greater redistribution of fat from subcutaneous to visceral regions, thereby contributing to a proinflammatory environment, insulin resistance, hypertriglyceridemia and the metabolic syndrome.7,8 Importantly, weight loss not only raises levels of HDL-cholesterol (HDL-C) and lowers blood pressure, glucose, waist size, and TGs, but also decreases proinflammatory cytokines.9 Overall, meta-analyses have reported that for every kilogram of weight loss, TG levels decrease approximately 1.9% or 1.5 mg/dL.10,11

MACRONUTRIENT RECOMMENDATIONS

Macronutrient intake, including both the amount and type of carbohydrate (CHO) and fat consumed, also significantly affects TG. CHO typically increases TG levels, as noted in the Evidence Statement from the National Cholesterol Education Program's Adult Treatment Panel (ATP) III: “...very high intakes of CHO (>60 percent of total calories) are accompanied by a reduction in HDL-C and a rise in TG.”12 Accordingly, ATP III recommended that “CHO intakes should be limited to 60 percent of total calories. Lower intakes (e.g., 50 percent of calories) should be considered for persons with Metabolic Syndrome who have elevated TG or low HDL-C.”12 However, a high-fiber (∼30 g/d), Dietary Approaches to Stop Hypertension (DASH)-style diet that is high in fruits and vegetables, whole grains, low-fat dairy products, and lean proteins may prevent the increase in TG seen with a higher-CHO diet.

Added sugars, a high glycemic index/load, and fructose all can increase TG. In the National Health and Nutrition Examination Survey 1999 to 2006 data set, the lowest TG levels were observed when added sugar was less than 10% of energy intake.13 Conversely, higher TG levels (by 5%–10%) were observed when added sugar intake was higher.13 Fructose increases postprandial TG, and while the effect of glycemic load on TG is controversial, some studies show benefits of a low glycemic load on TG. Although moderate alcohol consumption (up to 1 oz/d), is unlikely to have an appreciable effect on TG levels, more excessive consumption has been associated with hypertriglyceridemia. Factors that increase the risk of exaggerated rises in TG levels that on rare occasions may trigger pancreatitis include high quantities of alcohol consumption combined with a high saturated fat diet in the presence of an elevated baseline TG level (e.g., >250 mg/dL).

ROLE OF OMEGA-3 INTAKE

Many studies have shown that marine-derived omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexanoic acid [DHA]) decrease TG. In fact, EPA + DHA are used pharmacologically to treat elevated TG (>500 mg/dL); 2 to 4 g/d is recommended.14 Overall, each 1 g of EPA or DHA (either singly or combined) is associated with an approximate 5% to 10% reduction in TG levels. In contrast, non– marine-based omega-3 fatty acids, such as alpha-linolenic acid derived from flaxseed oil, do not seem to exert a significant effect on serum TG. Whether and to what extent the more recently promoted omega-3 products, such as krill oil, effectively reduce TG levels remains unclear due to the lack of published studies in hypertriglyceridemic subjects.

There is considerable evidence that a Mediterranean-style dietary pattern, high in fruits, vegetables, and dietary fiber and moderate in total fat provided by unsaturated fat (including marine-derived omega-3 fatty acids), is associated with a 10% to 15% lowering of TG, and a reduced prevalence of hypertriglyceridemia vs. a low-fat diet. Although previous recommendations for low-fat diets were associated with increased CHO intakes, the current AHA statement agrees in principle with ATP III, which calls for total fat intake between 25% and 35% of calories and targets the higher ranges of fat (as unsaturated fat in place of CHOs) for those with diabetes and metabolic syndrome risk factors such as elevated TGs. Restriction of saturated fat (e.g., <5% of total calories with TG levels ≥200 mg/dL) and elimination of trans fats are advocated in the AHA scientific statement.1

Optimization of nutrition-related practices can result in a marked TG-lowering effect that ranges from 20% to as high as 50% or greater. As summarized earlier and in Table 1, these practices include weight loss, reducing simple CHOs, increasing dietary fiber, restricting fructose (e.g., 50–100 g daily with TG between 200–499 mg/dL and <50 g with TG levels ≥500 mg/dL), consuming marine-derived omega-3 fatty acids, and implementing a Mediterranean-style diet. Elevated TG levels are associated with excess body weight, especially visceral adiposity; overabundant intake of simple CHOs, including added sugars and fructose; a high glycemic load; and excessive alcohol intake as discussed earlier.

Table 1
Table 1:
Effects of Nutrition Practices on TG Lowering

NONDIETARY RECOMMENDATIONS

There are 2 notable nondietary recommendations in the recent AHA statement: (1) Nonfasting measurements are recommended to screen for a high TG (≥200 mg/dL); and (2) an “optimal” fasting TG level (<100 mg/dL) is added to the existing ATP III classifications for borderline-high (150–199 mg/dL), high (200–499 mg/dL), and very high (≥500 mg/dL) TG. The rationale for the use of nonfasting measurements is based on numerous studies that have shown a negligible effect on blood TG levels after a low-fat meal (up to 15 g) has been consumed.1 Therefore, a light breakfast or snack would be acceptable for a patient who is interested in having a blood lipid screen in the absence of an overnight fast and for whom a calculated LDL cholesterol (LDL-C) level is not required. If a calculated LDL-C is required, then a standard fasting blood sample is needed. Provided that the nonfasting TG level is less than 200 mg/dL, only follow-up surveillance would be recommended as required. However, if nonfasting TG levels were at or exceeded 200 mg/dL, then a fasting lipoprotein profile is recommended to determine the severity of hypertriglyceridemia present (e.g., high or very high) to implement the best management strategies to reduce TG levels.

Designation of an optimal TG level (<100 mg/dL) reflects evidence that these values are consistent with cardiometabolic health. This is especially useful when patients review their lipid panel and want to engage in a “risk” conversation with their clinician. Specifically, optimal TG levels are associated with low visceral fat content,15 reduced incidence of type II diabetes mellitus (T2DM),16 and lower overall CV risk.1 Importantly, the AHA Scientific Statement did not recommend pharmacologic therapy to lower fasting TG levels to the optimal range, although that was recently interpreted to have been the case.17 In fact, the AHA statement was very careful to spell out the basis for the optimal TG level as stated: “An optimal triglyceride cut point is only intended to define one physiological parameter of cardiometabolic health. It does not represent a therapeutic target, because there is insufficient evidence that lowering triglyceride levels improves CVD risk prediction beyond LDL-C and non–HDL-C target goal recommendations. Nevertheless, the 25% rise in triglyceride levels in US adults during the past several decades that has coincided with higher caloric intake and higher rates of juvenile obesity and T2DM is of great concern. These developments have provided the impetus for intensification of efforts aimed at therapeutic lifestyle change to halt and potentially reverse an alarming trend that, if not proactively addressed, may eradicate the considerable progress in CVD risk reduction that has been achieved in recent years.”

TG SCREENING AND MANAGEMENT

An algorithm summarizing the AHA recommendations for screening and management of elevated TGs is presented in Figure 1. These recommendations are consistent with ATP III guidelines in as much as reduction in TG was recommended as a primary therapeutic goal only for patients with levels at or exceeding 500 mg/dL. The recommendation reflects concern for an increased risk of pancreatitis, especially with levels exceeding 1000 mg/dL.1 In patients with a history of hypertriglyceridemia-induced pancreatitis, the following caveats are noteworthy. First, it is necessary to optimize glycemic control in individuals with diabetes who are prone to high TG. Second, eliminate all commonly associated precipitants including alcohol, estrogen preparations, corticosteroids, and medications such as retinoic acid used for the treatment of acne. Although no randomized clinical trials have examined whether combining these modalities with TG-lowering therapies (e.g., fibrates, nicotinic acid, and marine-derived omega-3) reduces incident or recurrent pancreatitis, clinical experience from lipid experts suggests that the risk of not treating these patients exceeds the relatively modest cost and potential adverse effects of treatment.

Figure 1
Figure 1:
Practical algorithm for screening and management of elevated triglycerides. EPA/DHA, eicosapentaenoic acid/docosahexaenoic acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid; TFA, trans fatty acid.*When patients present with abdominal pain due to hypertriglyceridemic pancreatitis, removal of all fat from the diet is required (with the possible exception of medium chain triglycerides) until appropriate therapies lower triglyceride levels substantially. Reprinted with permission from Reference 1.

Although randomized clinical trial data also are scant in the determination as to whether TG-lowering therapies reduce CV event rates, subgroup analysis from several clinical trials identified patients with elevated TGs (i.e., >200 mg/dL) and reduced HDL-C to be at highest risk of a primary or recurrent CV event, and that TG lowering was associated with reduced risk.1 Unfortunately, none of these studies was performed in a cohort consisting entirely of hypertriglyceridemic patients and, therefore, it remains to be established whether lowering borderline-high and higher TG improves CV outcomes beyond other proven therapies. (See the related article on page 5.) Until such studies are completed, pharmacologic therapy for elevated TGs (i.e., 200– 500 mg/dL) is based upon levels of non–HDL-C after therapeutic LDL-C goals have been attained.12

REFERENCES

1. Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–2333
2. Mundi MS, Karpyak MV, Koutsari C, et al. Body fat distribution, adipocyte size, and metabolic characteristics of nondiabetic adults. J Clin Endocrinol Metab. 2010;95:67–73
3. Van Pelt RE, Jankowski CM, Gozansky WS, et al. Lower-body adiposity and metabolic protection in postmenopausal women. J Clin Endocrinol Metab. 2005;90:4573–4578
4. Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond). 2010;34:949–959
5. Tan GD, Goossens GH, Humphreys SM, et al. Upper and lower body adipose tissue function: a direct comparison of fat mobilization in humans. Obes Res. 2004;12:114–118
6. Karpe F, Tan GD. Adipose tissue function in the insulin-resistance syndrome. Biochem Soc Trans. 2005;33(pt 5):1045–1048
7. Sepe A, Tchkonia T, Thomou T, et al. Aging and regional differences in fat cell progenitors—a mini-review. Gerontology. 2011;57:66–75
8. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–359
9. You T, Nicklas BJ. Chronic inflammation: role of adipose tissue and modulation by weight loss. Curr Diabetes Rev. 2006;2(1):29–37
10. Anderson JW, Konz EC. Obesity and disease management: effects of weight loss on comorbid conditions. Obes Res. 2001; 9(suppl 4):326S-334S.
11. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320–328
12. National Cholesterol Education Program (U.S.). Third report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): final report. NIH publication no. 02-5215. Washington, DC: National Institutes of Health, National Heart, Lung, and Blood Institute; 2002.
13. Welsh JA, Sharma A, Abramson JL, et al. Caloric sweetener consumption and dyslipidemia among US adults. JAMA. 2010;303:1490–1497
14. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747–2757
15. Nicklas BJ, Penninx BW, Ryan AS, et al. Visceral adipose tissue cutoffs associated with metabolic risk factors for coronary heart disease in women. Diabetes Care. 2003;26:1413–1420
16. Balkau B, Lange C, Fezeu L, et al. Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care. 2008;31:2056–2061
17. Hirsch RL. Why even set an optimal level? Journal WATCH. July 19, 2011;.

Supplemental Digital Content

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