Lipid lowering with diet or dietary supplements
Christine C Tangney, PhD
Robert S Rosenson, MD
UpToDate performs a continuous review of over 330 journals and other resources. Updates are added as important new information is published. The literature review for version 13.3 is current through August 2005; this topic was last changed on August 30, 2005. The next version of UpToDate (14.1) will be released in February 2006.
INTRODUCTION ? Lipid alterations can also be effected by a number of dietary approaches or specific dietary supplements [1,2]. Such approaches have been exploited by nutritionists and physicians as evidence-based and less costly alternatives to several classes of drugs. These differ with respect to mechanism of action and to the degree and type of lipid lowering. Thus, the indications for a particular dietary supplement are influenced by the underlying lipid abnormality.
The characteristics and efficacy of the lipid-lowering dietary supplements or dietary components will be reviewed here.
FISH OIL ? Populations with high intakes of omega-3 (n-3) polyunsaturated fatty acids (such as the Eskimos) have low rates of heart disease; this observation has increased interest in the possible benefit of fish oils [3,4]. Rich sources of omega-3 fatty acids fatty acids come from fatty fish, especially salmon, and plant sources such as flaxseed and flaxseed oil, canola oil, soybean oil, and nuts. (See "Dietary fat").
Fish oil concentrate administered at high doses (>6 g/day) can reduce levels of triglycerides through inhibition of the synthesis of VLDL-triglycerides and apolipoprotein B [5,6]. In hypertriglyceridemic subjects, fish oils (in a dose of 15 g/day) lower triglyceride levels by approximately 50 percent [7,8].
Since fish oil lowers plasma triglyceride concentration, which in turn is a determinant of small dense LDL, it is possible that fish oils will decrease the concentration of smaller LDL. Support for this hypothesis comes from the observed reduction of cholesteryl ester transfer activity following fish oil therapy [9]. In addition, several studies have observed an increase in overall LDL particle size with 4 g purified docosahexaenoic acid [10-12]. In contrast, 2.5 g of omega-3 fatty acids daily for two months did not significantly change this fraction in 16 non-insulin-dependent diabetics when compared to placebo [13].
Ingestion of fish oils is associated with a variety of clinical benefits [14]. These benefits may be due to effects other than improved blood lipid profiles. These include reductions in blood pressure, arrhythmia, and coagulability, and improvement in endothelial function [15]. The benefit may correlate with blood long-chain omega-3 fatty acid levels [16].
A meta-analysis of 11 studies involving 16,806 patients found that, compared to a control diet or placebo, a diet enriched with omega-3 fatty acids or the use of supplements was associated with significant reductions in fatal infarction (risk ratio 0.7, 95% CI 0.8-0.8), sudden death (risk ratio 0.7, 95% CI 0.6-0.9), and total mortality (risk ratio 0.8, 95% CI 0.7-0.9) [14]. The benefits were the same for an enriched diet or supplements. (See "Overview of sudden cardiac death", section on Fish intake and fish oil).
The range of benefits in different populations can be illustrated by the following findings:
* A prospective study of 1871 men aged 42 to 60 who did not have clinical heart disease at a baseline examination found that men with the highest intake of fish oils had a 44 percent lower incidence of acute coronary events after 10 years compared to those with the lowest intake [3]. The risk reduction was higher (67 percent) when hair content of mercury was low, suggesting that a high mercury content in fish could attenuate this protective effect. (See "Overview of the risk factors for cardiovascular disease", section on Mercury).
* A double-blind, placebo controlled trial of 233 patients with angiographic evidence of CHD found that, compared to placebo, 6 g of fish oil concentrate daily for three months and 3 g/day for 21 months resulted in an improvement in angiograms and a moderate reduction in cardiovascular events [17].
* The GISSI Prevention study randomly assigned 11,324 patients within three months of a myocardial infarction to a fish oil supplement (1 g daily), vitamin E (300 mg daily), both, or neither [18]. Patients receiving fish oil had a significantly lower incidence of the combined end point of death plus nonfatal infarction and nonfatal stroke at 42 months (12.6 versus 13.9 percent for no fish oil); all the beneficial effect was due to a 20 percent reduction in the risk of death, a 30 percent reduction in cardiovascular death, and a 45 percent reduction in sudden death. The reduction in sudden death was statistically significant at four months after randomization (relative risk 0.47), while the reduction in cardiovascular, cardiac, and coronary deaths became significant at six to eight months [19]. The benefit of fish oil was maintained at a five year follow-up [20].
* In an analysis from the Physicians' Health Study, the risk of sudden death was significantly lower in subjects with blood long-chain n-3 fatty acid levels in the highest, compared with the lowest, quartile (adjusted relative risk 0.19, 95% CI 0.05-0.71) [16]. The degree to which fish or fish oil intake was responsible for differences in fatty acid concentrations was not reported.
* In a prospective study of 4185 older adults in the Cardiovascular Health Study, consumption of tuna or other broiled or baked fish, but not consumption of fried fish or fish sandwiches, correlated with plasma n-3 fatty acids [21]. During 12 years of follow-up, compared with consumption less than once per month, people who consumed tuna or other broiled or baked fish one to four times per week or five or more times per week had a lower incidence of atrial fibrillation (AF) (hazard ratio of 0.72 and 0.69, respectively); consumption of fried fish or fish sandwiches was not associated with a lower risk of AF.
Side effects ? There are a number of undesirable effects of high dose fish oil administration:
* The generation of lipid peroxides and a fall in circulating levels of vitamin E [22,23]. Vitamin E supplementation (200 mg/day) can restore vitamin E levels [24]. (See "Overview of fat-soluble vitamins").
* Gastrointestinal side effects including nausea, eructations, abdominal bloating, flatulence, diarrhea, and a fishy aftertaste. The symptoms often limit the use of fish oil.
* Some studies have suggested that glycemic control worsens in patients with type 2 diabetes mellitus who consume fish oil [25]. However, a meta-analysis of 26 trials found that the fish oil had no adverse effects on hemoglobin A1c in diabetics [26].
Recommendations ? At least two servings of fish per week are recommended to confer cardioprotective effects [27]. The pharmacologic use of fish oils supplements should be restricted to patients with refractory hypertriglyceridemia and periodic monitoring of apolipoprotein B levels is recommended. The use of fish oil for this purpose is discussed in detail separately. (See "Approach to the patient with hypertriglyceridemia").
SOY ? Soy, an excellent source of protein, also contains isoflavones, which are phytoestrogens. Isoflavones are micronutrient substances that, in nonhuman primates, have properties similar to estrogen, including an effect on cholesterol levels and inhibition on low density lipoprotein (LDL) oxidation [28]. It has been suggested that the lower risk of heart disease among Asian compared to Western populations is due to the high consumption of soybean products. A meta-analysis of 38 controlled clinical trials found that, compared to a control diet, soy protein (average intake 47 g/day) lowered total serum cholesterol by 9.3 percent, LDL-cholesterol (LDL-C) by 12.9 percent, and triglycerides by 10.5 percent, while HDL-cholesterol (HDL-C) concentration increased by 2.4 percent; the changes in total cholesterol and LDL-C were directly related to the initial serum cholesterol concentration [29].
In order to establish the agent responsible for the beneficial effect of soy protein, one study randomized 156 subjects with serum cholesterol levels between 140 and 200 mg/dL (3.6 to 5.2 mmol/L) to a diet containing casein (protein without isoflavones) or one of four diets that included soy protein containing 3 to 62 mg of isoflavones [30]. Compared to the casein-containing diet, a diet containing greater than or equal to37 mg of isoflavones lowered total and LDL-C by 4 and 6 percent, respectively; there was a dose-response effect of increasing amounts of isoflavones on cholesterol concentrations, and the greatest reduction was seen in patients with serum cholesterol values >164 mg/dL (>4.2 mmol/L. Another dose-response study of hypercholesterolemic men on a NCEP Step I diet examined if a threshold exists for dietary soy protein. All levels of soy protein, 20 to 50 g/day for six weeks, led to reductions in blood lipids with higher levels being most effective [31].
It is not clear that soy protein improves plasma lipids in postmenopausal women, particularly among those with borderline hypercholesterolemia. In contrast to a number of shorter-term studies, a one-year randomized trial of soy protein containing 99 mg of isoflavones in 202 healthy postmenopausal women in the Netherlands found no significant effect on lipid measurements including levels of total cholesterol, HDL-C, LDL-C, and lipoprotein(a) [32]. In a three-month study that included both men and postmenopausal women ages 50 to 75, compared with casein placebo, a slightly higher level of isoflavones (40 g soy; 118 mg isoflavones) only significantly improved LDL/HDL ratios and triglyceride concentrations [33].
Another possible mechanism for the reduction of coronary heart disease related to the intake of soy proteins is the effect of phytoestrogens on coronary arteries. One animal study found that phytoestrogens produced endothelium-independent relaxation of coronary arteries as a result of calcium antagonism [34]. Studies in healthy humans found that the phytoestrogen genistein caused endothelium-dependent vasodilation with a similar potency to estradiol [35-37]. This beneficial effect on endothelial function, in the absence of any change in lipids, may be related to soy isoflavones, without soy protein [35,37,38]. It is possible that both soy protein and isoflavones may be needed for the maximal cholesterol-lowering effect [39].
The ingestion of soy protein also may be associated with adverse effects. As an example, in a study of 108 men and 105 postmenopausal women (all healthy), soy protein improved both blood pressure and lipids, but did not improve vascular function as measured by systemic arterial compliance and pulse wave velocity. Adverse effects included an increase in serum Lp(a) and a decline in endothelial function (in men only) [33]. (See "Preparations for postmenopausal hormone therapy", section on Phytoestrogens).
It is not clear whether the estrogen-like activities of isoflavones increase the risk of breast cancer, as they may increase breast secretions and the proliferation of breast epithelium. Thus, there are no specific recommendations regarding the intake of soy protein in the diet or as supplements. It may be reasonable to caution women at increased risk for breast cancer against high soy intake. (See "Postmenopausal hormone therapy and the risk of breast cancer").
Recommendation ? An advisory from the Nutrition Committee of the American Heart Association concluded that clinical trials have found 25 to 50 grams/day of soy protein to be safe and effective for reducing LDL-C by 4 to 8 percent; it recommended that the daily consumption of a minimum of 25 grams of soy protein be included in a diet low in saturated fat and cholesterol to promote heart health [40]. Subsequent data call into question the effectiveness of soy protein in reducing LDL-C levels in postmenopausal women [32].
RED YEAST RICE ? Red yeast rice is a fermented rice product that has been used in Chinese cuisine and medicinally to promote "blood circulation" [41]. The product contains varying amounts of a family of naturally occurring substances called monacolins that have HMG CoA reductase inhibitor activity [42]. (See "Lipid lowering with statins"). Other active ingredients in red yeast rice that may affect cholesterol lowering include sterols (beta-sitosterol, campesterol, stigmasterol, sapogenin), isoflavones, and monounsaturated fatty acids [43].
The efficacy of red yeast rice for cholesterol lowering was evaluated in a prospective, double-blind study in which 83 patients with hyperlipidemia (total cholesterol 204 to 338 mg/dL [5.28?8.74 mmol/L], LDL-C 128 to 277 mg/dL [3.31?7.16 mmol/L]) who were not receiving cholesterol lowering therapy were randomly assigned to receive red yeast rice (2.4 g/day) or placebo; both groups were also were advised to follow a cholesterol lowering diet [43]. The following results were reported:
* The total cholesterol concentration decreased significantly between baseline and 8 weeks in the red yeast rice compared with the placebo-treated group (208 versus 251 mg/dL [5.38 vs 6.57 mmol/L]).
* The LDL-C concentration also decreased significantly in the red yeast rice group (135 versus 175 mg/dL [3.49 versus 4.53 mmol/L]).
* HDL-C was unaffected.
One of the monacolins in the red yeast rice extract used in this study, monacolin K, is the active ingredient in the HMG CoA reductase inhibitor lovastatin. The daily lovastatin content of red yeast rice was 0.2 percent of the total product, which at a total dose of red yeast rice of 2.4 g/day translates into a daily lovastatin dose of 4.8 mg. This is considerably lower than the average 20 to 40 mg dose of lovastatin used in clinical trials of cholesterol lowering, suggesting that other active ingredients in red yeast rice probably also contributed to its cholesterol lowering activity [42].
Other studies have also found that red yeast rice lowers total and LDL-C [44]. However, not all strains of red yeast rice are alike and results of these clinical trials may not generalize to different preparations. As an example, in a study that evaluated the content of nine preparations of commercially available red yeast rice, the total monacolin content varied from 0 to 0.58 percent and only 1 of 9 preparations had a full complement of 10 monacolin compounds [45]. Furthermore, while short-term studies (up to four months) have found red yeast rice to be safe, no long-term studies have been performed [42].
In summary, red yeast rice may have cholesterol lowering ability due to the presence of monacolins that have HMG CoA reductase inhibitor activity, and possibly other active substances. However, these extracts suffer from the same problem as many other natural products, that is, a lack of standardization. (See "Overview of herbal medicine", section on Lack of standardization.) Furthermore, long-term safety data are not available.
GUGGULIPID ? Guggulipid is a preparation containing standardized guggul, an extract from the resin of the mukul myrrh tree that has been used as a treatment for hypercholesterolemia.
However, a randomized, placebo-controlled trial in the United States involving 103 adults with hypercholesterolemia found that LDL levels increased significantly with three times daily guggulipid (1000 mg and 2000 mg) compared with placebo (+4 and +5 versus -5 percent); hypersensitivity rash occurred in 5 of 34 patients in the higher dose guggulipid arm and 1 of 33 patients in the lower dose arm [46].
Randomized trials in India have found that guggulipid decreased total cholesterol and LDL-C concentrations [47,48]. The authors of the US study suggested that possible explanations for the differing results between the Indian and US studies include differences in the populations' genetics, diet, and body fat composition. Additionally, though, methodologic concerns have been raised about both Indian studies. These include that one of the trials [47] did not have a placebo arm. A further issue for the other Indian study [48] is that concerns have been raised about the accuracy of other papers published by these same authors [49-52].
We do not recommend the use of guggulipid for treatment of hypercholesterolemia until further efficacy and safety data are available.
POLICOSANOL ? Policosanol is a drug extracted from sugar cane wax. It contains a number of aliphatic alcohols. It appears to be well tolerated and some studies suggest that at doses of 10 to 20 mg daily it can reduce LDL-C concentrations by as much as 25 percent or more [53,54].
There are only limited data on clinical endpoints. Additionally, there is variability in the available preparations such that the exact composition is uncertain, and the effective components and mechanism of action are relatively unknown. We do not recommend the use of policosanol for the treatment of hypercholesterolemia until further efficacy and safety data are available.
GARLIC ? Garlic has been advocated as an effective method to lower serum cholesterol concentrations. However, data are conflicting [55-58]. A meta-analysis of selected trials found that garlic tablets reduced serum cholesterol concentrations by approximately 9 percent [59]. However, many of the included trials did not perform standard laboratory measurements and did not control or monitor dietary compliance. A second meta-analysis found similar short-term effects of garlic in lowering the total cholesterol, and also noted parallel reductions in LDL-C and triglycerides [60]. However, reductions did not persist beyond six months, and the authors commented that conclusions regarding clinical significance are limited by the marginal quality and short duration of many trials, and by the inadequate definition of active constituents in study preparations.
This issue was addressed more directly by several studies:
* Two small randomized studies of 50 patients each showed no benefit of garlic on lipids and lipoprotein concentrations [55,56].
* In contrast, another randomized trial administered garlic (900 mg/day) alone or together with fish oil (12 g/day) to 50 mildly hypercholesterolemic males [57]. At 12 weeks, total cholesterol and LDL-C levels fell significantly (11 and 14 percent, respectively), but there was no change in triglyceride or HDL-C concentrations. Garlic supplementation significantly decreased both total cholesterol and LDL whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentration; the combination of garlic and fish oil reversed the moderate fish oil-induced rise in LDL.
* In a double-blind crossover study of 56 men with moderate hypercholesterolemia who were also placed on an NCEP Step I diet, a large dose of garlic supplement (7.2 g) significantly lowered total and LDL-C concentrations by 6 and 4 percent, respectively, after six months [58].
CHOLESTEROL-LOWERING MARGARINES ? Cholesterol-lowering margarines enriched with plant sterols are now available [61]. Plants contain a number of sterols. Two saturated plant stanols, sitostanol and campestanol, are the main sterols present in the one of the products currently available in the United States, Benecol; sitosterol and campesterol are the major plant sterols found in the other product, Take Control. Daily intake of 0.8 to 3 g of plant stanols and/or sterols in these margarines appears to lower serum cholesterol levels [62].
Plant sterols are similar in chemical structure to cholesterol, differing in their side chain configuration. The mechanism by which they lower cholesterol is thought to involve inhibition of cholesterol absorption [63,64]. However, the decrease in serum cholesterol is less than that expected by the degree of reduced absorption, likely because of a compensatory increase in hepatic cholesterol synthesis [62].
A number of studies have examined the efficacy of plant stanol- and sterol-enriched margarines for lowering cholesterol:
* One study randomly assigned 153 patients with mild hypercholesterolemia to consumption of margarine fortified with sitostanol or to unfortified margarine [62]. Those consuming the fortified margarine had a 10 to 14 percent decrease in total and LDL-C that occurred predominantly in the first three months, although values continued to decline over the twelve months of the study. There was no significant difference in HDL-C and triglycerides between the two groups. Absorption of fat soluble vitamins did not appear to be affected, although serum beta-carotene levels were significantly lowered. The participants could distinguish between the two margarines by taste, although could not decide which tasted better.
* A second study of sitostanol fortified margarine (3 g per day) in 22 postmenopausal women with coronary heart disease found that total and LDL-C were lowered by 13 and 20 percent compared to 5 percent in women consuming unfortified margarine [60]. In a second group of 10 women on simvastatin, consumption of sitostanol fortified margarine for 12 weeks reduced the dose of simvastatin necessary to reach the target level of cholesterol.
* A third trial compared consumption of margarines supplemented with sitostanol (Benecol) to those with sterols from soybean, sheanut, or rice bran oil (mainly beta-sitosterol, campesterol, and stigmasterol), or to unfortified margarine in 100 patients with normal cholesterol or mild hypercholesterolemia [65]. The target amount of these margarines, 30 g per day, was achieved for most participants with total plant sterol or stanol intakes ranging from 1.7 to 3.2 g day, largely due to variations in plant sterols in supplemented spreads. Sheanut and rice bran oil based margarines contained lower (around 48 percent) and different plant sterols when compared to the sitostanol and soybean oil products. Both soybean and sitostanol containing margarines lowered total and LDL-C by 8 to 13 percent compared with controls, without affecting HDL-C.
Stanol-enriched margarine can also reduce cholesterol in patients receiving a stable dose of a statin drug. As an example, one series of 167 subjects with an LDL-C greater than or equal to130 mg/dL, despite at least three months of statin therapy, found that 5.1 g per day of plant stanol ester for eight weeks reduced total cholesterol by 12 percent (versus 5 percent for placebo) and LDL-C by 17 percent or 24 mg/dL (versus 7 percent and 10 mg/dL for placebo) [66].
These short-term studies have shown no adverse effects of consumption of margarines fortified with plant sterols/stanol esters. It is possible over the long-term that they can cause reduction in plasma concentrations of antioxidants such as beta-carotene and alpha tocopherol [62]. Several studies have found only minimal impact of these margarines on circulating levels of fat-soluble vitamins [67-70]. Furthermore, another report suggested that consuming one additional serving per day of a high carotenoid vegetable or fruit counteracted any effects of the margarine in lowering plasma carotenoids [71]. However, none of these studies were more than three weeks in duration.
There have been no studies demonstrating that consumption of these stanol ester-containing margarines influences the incidence of coronary heart disease. Concerns related to the accumulation of plant sterols do not apply to these products since stanol esters are not absorbed, unlike plant sterols; they protect against the potential accumulation associated with beta-sitosterolemia.
Recommendations ? An advisory from the Nutrition Committee of the American Heart Association concluded that although foods containing plant sterols/stanol esters are a promising addition to dietary intervention aimed at improving cardiac risk profiles, these products should not be used routinely by the general population until long-term studies are performed to ensure the absence of adverse effects; their use should be reserved for adults with hypercholesterolemia or an atherosclerotic event who require lowering of total and LDL-C levels [72]. Although they can be used in hypercholesterolemic children, fat-soluble vitamin status should be monitored. It is uncertain if plant sterols/stanol esters should be used in normocholesterolemic individuals who have risk factors for coronary artery disease, for example those with low HDL-C. The manufacturer recommends the following doses of plant sterol/stanol esters fortified margarines:
* Take Control: Two tablespoons per day (1120 mg sitosterol per tablespoon [14 g] serving)
* Benecol: Three servings per day (1.5 g sitostanol per 1 1/2 teaspoon [8 g] serving.
Their cost is approximately five times that of ordinary margarine [73].
MARGARINES AND PRODUCTS LOW IN TRANS-FATTY ACIDS ? Some trans fatty acids occur naturally in foods, especially those of animal origin, although most trans unsaturated fatty acid consumption is a result of the industrial hydrogenation of polyunsaturated fatty acids, such as in vegetable oil [27]. Numerous prepared foods such as cakes, cookies, commercially prepared fried foods, and some margarines may have a high content of trans unsaturated fatty acids. (See "Dietary fat"). Trans unsaturated acids can increase LDL-C and reduce HDL-C, while the consumption of foods that are low in trans unsaturated fatty acids (<0.5 g per 100 g), such as soybean oil and semiliquid margarine, have beneficial effects [74,75]. Future inclusion of trans unsaturated fatty acids on food labels, as well as increasing the availability of trans fatty acid-free products, will aid in reducing current intake.
FIBER ? Limiting intakes of saturated and transunsaturated fatty acids requires the substitution of other nutrients, unless there is a concomitant need to reduce energy intake as well. Substitution of carbohydrate leads to reduction in LDL-C, but in the absence of weight loss, extremely high proportion of carbohydrates (>60 percent of energy) can elevate triglycerides levels and lower HDL-C [76,77]. Such changes are lessened with the incorporation of greater amounts of fiber, in which carbohydrate is derived from unprocessed whole foods [78].
Certain soluble fibers (psyllium, pectin, guar gum, and oat products) will reduce LDL. In a recent meta-analysis, every gram increase in soluble fiber reduced LDL-C by an average of 2.2 mg/dL (0.057 mmol/L); this effect was similar with various soluble fibers [79]. The addition of psyllium supplementation may result in small further reductions in LDL-C concentrations in patients receiving low dose statin therapy [80].
NUTS ? Small randomized trials have shown that walnuts, which are rich in polyunsaturated fatty acids, have a beneficial effect on serum lipids when compared to other cholesterol lowering diets. As examples, one compared a Mediterranean diet to a diet in which walnuts replaced 35 percent of the energy obtained from monounsaturated fats [81], and one compared a National Cholesterol Education Program step 1 diet to a similar diet in which walnuts accounted for 20 percent of calories [82]. The following respective benefits were noted with the walnut diets compared to the control diets: a 4 and 12 percent reduction in serum total cholesterol; and a 6 and 12 percent reduction in serum LDL-C. Another small, randomized trial suggested that in addition to lowering total and LDL-C levels, consumption of walnuts may improve endothelial function in patients with elevated cholesterol [83].
Other nuts may also be effective. As an example, one study found that isoenergetic increases in almond intake improved the lipid profiles of healthy and mildly hypercholesterolemic adults; when compared with a step 1 diet, replacement of approximately 20 percent of energy with almonds (68 g) led to marked improvements in lipids within four weeks [84].
There is also evidence that increased nut intake is associated with improved cardiovascular outcomes. In a review from the prospective Adventist Health Study, individuals who consumed nuts more than four times per week had significant reductions in mortality from coronary heart disease (relative risk 0.52) and in nonfatal infarctions (relative risk 0.49) compared to those who consumed nuts less than once per week [85].
Similar findings were noted in a report from the Physicians' Health Study [86]. After controlling for known cardiac risk factors and other dietary habits, men who consumed nuts two or more times per week had, when compared to men who rarely or never consumed nuts, significant reductions in total coronary deaths and sudden cardiac deaths (relative risk 0.53 and 0.70, respectively). In contrast to the Adventist Health Study, there was no reduction in nonfatal infarction; this could have been related to lower nut intake in the Physicians' Health Study.
TEA ? A randomized trial of theaflavin-enriched green tea extract in 240 people on a low-fat diet with mild to moderate hypercholesterolemia found that once daily tea extract (75 mg theaflavins, 150 mg green tea catechins, 150 mg other tea polyphenols) improved lipid profiles [87]. Over 12 weeks, tea extract significantly lowered total and LDL-C concentrations compared with placebo (-27.6 versus -1.7 mg/dL [-0.71 versus -.04 mmol/L] and -26.1 versus +0.5 mg/dL [-0.67 versus 0.0 mmol/L], respectively) without significantly affecting HDL concentrations. The extract studied is commercially available as Teaflavin® at
www.nashai.com.
CALCIUM ? Human and animal studies have suggested that calcium intake may affect the serum lipid concentration by binding to fatty acids and bile acids in the gut, thereby interfering with lipid absorption [88,89]. In addition, at least two randomized, controlled trials have found that calcium supplementation causes beneficial changes in circulating lipids [90,91].
As an example, one study randomly assigned 223 postmenopausal women, who were not receiving therapy for hyperlipidemia or osteoporosis, to receive calcium (1 g/day) or placebo [91]. After 12 months, the HDL-C concentration and HDL to LDL-C ratio had increased significantly more in the calcium than cholesterol group (change from baseline for HDL 4.64 versus 1.16 mg/dL [0.12 versus 0.03 mmol/L]; change in ratio 0.07 versus 0.02). Furthermore, there is some observational evidence in postmenopausal women that calcium intake is inversely associated with cardiovascular disease [92].
However, beneficial effects on serum lipids were not noted in another randomized trial of 193 men and women ages 30 to 74 years [93]. The cause for the discrepant findings is uncertain but may be related to differences in the patient populations that were studied.
COMBINATION DIET
Multiple components ? A diet that includes diverse cholesterol-lowering components may be particularly effective in lowering lipid levels. A study that compared a diet very low in saturated fat, a diet very low in saturated fat plus lovastatin 20 mg/day, and a diverse diet high in plant sterols (1 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) found reductions in LDL-C concentration over a one month period of 8.0, 30.9, and 28.6 percent respectively; there was no statistically significant difference between the group receiving statin therapy and the group receiving the diverse diet [94].
Mediterranean diet ? A Mediterranean diet may decrease the risk of heart disease (CHD). There is no single Mediterranean diet, but such diets are typically high in fruits, vegetables, whole grains, beans, nuts, and seeds and include olive oil as an important source of fat; there are typically low to moderate amounts of fish, poultry, and dairy products and there is little red meat.
A randomized trial in patients who had had a myocardial infarction found fewer subsequent cardiac events among those assigned to a Mediterranean diet [95]. (See "Clinical trials of cholesterol lowering in patients with coronary heart disease", section on Lifestyle modification). These results may in part be related to greater reductions in inflammatory markers and insulin resistance in patients eating a Mediterranean diet [96].
Diets that are identical in major nutrient categories but differ in fiber content may have different effects on lipids, especially when body weight is held relatively constant. A four-week randomized trial that compared two diets identical in total fat, saturated fat, protein, carbohydrate, and cholesterol content in 120 adults found that, compared with a typical US low fat diet, a diet that used more vegetables, legumes, and whole grains to achieve this content led to significantly greater reductions in total and LDL cholesterol concentrations [97]. The second diet contained more than twice the amount of fiber (both soluble and insoluble components).
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Discussion Zen 5 Speculation (EPYC Turin and Strix Point/Granite Ridge - Ryzen 9000)
Discussion Intel current and future Lakes & Rapids thread
