Introduction

Cardiovascular diseases (CVD) are the most prevalent cause of death and disability in both developed as well as developing countries.  INDIA is one of  the leading nations in ASCVD and is already a global capital of diabetes. In 2005, 29% of deaths in INDIA occurred  alone due to CVD.¹ According to the recent estimates about 2.9 crores India’s population is burdened with CVD and may increase to 6.4 crores,  if no early intervention steps are taken. Dyslipidemia has been found to be one of the most important contributing factors.²

Dyslipidemia describes a number of abnormalities in lipoprotein homeostasis including hypercholesterolemia and hypertriglceridemia.  Several co-morbid conditions like myocardial infarction, stroke, atherosclerosis, nephropathy, fatty liver cirrhosis and many others are  associated with dyslipidemia. Therefore, reductions in dyslipidemic conditions and eventually CHD risk begin with the adoption of a  healthy lifestyle. Thus, as a part of a comprehensive strategy to reduce complications of hypercholesterolemia, NCEP (National Cholesterol Education Programme) endorsed the use of several lipid lowering dietary agents.³

This review emphasize on the quantity of soy, flaxseeds, oats and psyllium that have shown to improve the lipid profile, the mechanisms  of each bioactive component responsible in reducing the risk of ASCVD and several human clinical trials data regarding their safety and  efficacy.

Bioactive Components

Dietary Fiber (DF) are the edible parts of plants or analogous carbohydrate that are resistant to digestion & absorption in the human  intestine with complete or partial fermentation in the large intestine and which promote beneficial physiological effects including laxation and blood glucose attenuation and /or blood cholesterol attenuation. Total dietary fiber (TDF) occurs in 2 major forms i.e. soluble  dietary fiber (SDF) and insoluble dietary fiber (IDF).⁴ DF content of various foods are mentioned in Table 1.

Table 1: Dietary fiber content of selected  foods.5,6 Click here to View table

Mechanism  of  Action

Soluble fiber lowers total and LDL-c cholesterol which can be attributed to enhanced gastric emptying, intestinal binding of bile acids  thus reducing entero-hepatic bile recirculation, lowered dietary cholesterol absorption, affects VLDL composition which then contains  more amount of phospholipids and less of cholesterol, also improves satiety. It also undergoes fermentation to short chain fatty acids  (SCFA) in the colon thus reducing endogenous synthesis of cholesterol. It also decreases dietary glucose absorption thereby down  regulating cholesterol synthesizing anabolic hormone insulin release.^7-13

Omega-3  Fatty  Acid  From  a  Plant  Source

They are essential fatty acids for competitive synthesis of eicosonoids which are anti-inflammatory, anti aggregatory and anti-thrombotic  in action.^{14, 15} Additional physiologic functions of omega-3 fatty acids which may prevent ASCVD include several mechanisms such as;  maintain fluidity of the cell membrane thus facilitating removal of  cholesterol, down regulating phosphotidic acid phosphatase (PAP)  and diacylglycerol acyl tranferase (DGAT) thus reducing fatty acid synthesis, also activates PPAR involved in B-oxidation of fatty acids,  upregualting lipoprotein lipase (LPL) activity thus increasing fats hydrolysis. N-3 fatty acids also modulate sterol regulating element  binding protein (SREBP) and increases degradation of apoprotein B which eventually decreases LDL-c secretion and transport.^16-18 Table 2 illustrates nutrient composition of flaxseed.

Table 2: Various Flaxseed Products  Composition Click here to View table

Phytoestrogens

Area diverse group of naturally occurring non steroidal plant compounds that, because of their structural similarity with estradiol (17-β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects.²⁰ Phytoestrogen content of selective foods are discussed in  Table 3. There are 2 major classes of phytoestrogens including: Isoflavones contains major bioactive components i.e. daidzein and genistein. They are primarily present in soy as much as 3 mg/g dry weight of soy. Lignans and their major bioactive components secoisolariciresinol and  matairesinol are primarily found in flaxseeds.²¹

Table 3:  Phytoestrogens content of foods. Click here to View table

Mechanism of  Action

Clinical evidence suggest that phytoestrogens is effective in lowering serum cholesterol via a series of mechanism which include; up regulation of LDL-c receptor activity thus increasing its clearance, it also depresses the activity of platelet activating factor receptor  antagonists eventually reducing oxidation of the lipid, the primary step in process of hypercholesterolemic atherosclerosis.  Phytoestrogens also enhances the activity of cholesterol-7 hydoxylase which in turn decreases endogenous cholesterol synthesis. There is  also down regulation of the enzyme tyrosine kinase thus reducing thrombin production and ultimately myocardial infarction risk (MI)  risk.^22-27

Soy  Protein

Recently soybeans are considered by many agencies as a source of a complete protein. Hence variety of food such as salad dressings,  beverage powders, cheese, infant formulas and others contains soy proteins. The nutritional value of soy protein is equivalent to that of  animal protein of high BV. For instance, isolated soy protein has a PDCAAS (Protein Digestibility Corrected Amino Acid Score) of 1.0,  which is the same as that of casein and egg protein. 100g of whole soybeans contains 43.2 g of protein.^28-30 Biological value of various  soy products like whole soybean, soy milk, soy protein isolates are 96.0, 91.0, and 74.0 respectively.³¹

Mechanism of Action

Various studies have shown that soy proteins effectively lowers cholesterol through series of mechanisms such as; it binds bile acids thus  reducing enterohepatic recirculation of bile, it also up regulates the apz B and apo E receptor activity thus reduces serum LDL-c levels.    Soy proteins have also shown to reduce HMG-CoA reductase activity, the rate limiting enzyme in cholesterol synthesis and increase cholesterol-7 hydroxylase activity which eventually lowers cholesterol synthesis.^31-33

Human  Studies

To identify the majority of human studies on cardiovascular effects of these food items we performed a systematic search of the following  databases: PubMed, Medscape, MDconsult etc from 1995-2009. We used the headings “soluble fiber, botanical n-3 fatty acids, Phytoestrogens and soy proteins and searched the terms “soy, flaxseeds, oats and psyllium.” Using this strategy we identified 75  relevant articles and book chapters. The description below highlights the information on potential CV application of this food items.

Epidemiological Data

Epidemiological data concerning in take of fiber, n-3fatty acids, phytoestrogens and soy proteins are studied as all the discussed food  items are a good sources of this bioactive components. Epidemiological data on dietary fiber and risk of ASCVD are extensive and suggest  in general an inverse correlation between them. Several observational trials have found positive correlation between soy proteins and n-3  fatty acids and secondary prevention of ASCVD. Also observational studies revealed that lignans may reduce ASCVD morbidity and  mortality. The following section describes data from human studies that addresses the Quantity and Effects of soy, flax, oats and  psyllium and their bioactive components on CV risk factors dyslipidemia and others like inflammation, blood pressure and glycemic  control.

Bioactive Components Enriched Food Items 

Soy 

Soy (glycine  max) is a species of legume native to East Asia. The beans contain significant amounts of proteins (38%), isoflavones,  dietary fiber (25-30%) and phytic acid. The principle carbohydrates (30-32%) of mature soybeans are the disaccharide sucrose (2.5-8.2%), trisaccharde raffinose (0.1-1.0%) and the tetrasaccharide stachyose (1.4-4.1%). The majority of soybean carbohydrates can be classed as  belonging to dietary fiber. The Food Drug and Administration (FDA) have approved soy as an official cholesterol-lowering food, along  with other heart and health benefits.³⁵ The major bioactive components that are responsible for improving the lipid profile on soy  interventions are dietary fiber, phytoestrogens and soy proteins and articles related to these are discussed in table 4.

Table 4: Interventional trial data on lipid  lowering effects of soy Click here to View table

To  Summarize

The bulk of the evidence from five clinical trials (36-41.) suggest that soy proteins (20-40g/d) or soy isoflavones (30-150mg/d) can  modestly but significantly (p=<0.05) reduce total and LDL cholesterol in both normal and hypercholesterolemic subjects, without a  significant effects on  HDL-c and TG’s. Effects were more prominent in post menopausal women or in subjects with initial mild to  moderate hypercholesterolemia. Desroches S., et al concluded that soy was also effective in shifting LDL particle size to a less  atherogenic pattern. Thus, replacing foods high in saturated fats, trans fats & cholesterol; by soy products containing 30-150 mg/d of isoflavones or    20-40g/d of soy protein have a positive effects against coronary risk factors and related co morbidities e.g.: type 2 DM, hypertension and  others.

Flaxseeds

Flaxseed (linseed) is a smooth, flat and reddish-brown in color is native to the region extending from the eastern Mediterranean to  INDIA. Whole flaxseeds contain 28% dietary fiber (7-10% soluble fiber, 11-18% insoluble fiber); 40% fats (57% of omega-3 fatty acids)  and 21% proteins. it is also the richest source of phtoestrogens-lignans.⁴² Consumption of flaxseeds have shown to reduce total and LDL  cholesterol as well as platelet aggregation (43,44.). The major bioactive components responsible for hypolipidemidic action of flaxseeds  are dietary fiber, omega-3 fatty acids and lignans and human trials related to these are discussed in detailed in table 5.

Table 5: Interventional trial data on lipid  lowering effects of flaxseeds Click here to View table

To  Summarize

The results of the above discussed 5 clinical trials (43-48.) suggest that flaxseeds (20-50g/d whole or partially defatted respectively) are  efficacious in improving the lipid profile in both normal and mild-moderate hypercholesterolemic subjects. This can be due to the  bioactive components in flax like fiber, n-3 fatty acids and lignans which via several mechanisms as discussed earlier have shown to have  a positive association with reductions in serum total and LDL cholesterol. The effects of flax seeds were more prominent in subjects with  initial hypercholesterolemia like in postmenopausal women. They have also shown to have beneficial effects on other CVD risk factors  like ratios of TC: HDL, LDL: HDL reductions in Apo B 100 and also Lp (A) a strong predictor of CVD. Thus daily incorporation of 20-50g  of whole or partially defatted seeds respectively is effective in improving lipid profile.

Oats

Oats most commonly are available as rolled, crushed into oatmeal or ground into oat flour. Oat bran is the outer casing of the oats. Oats  contain more soluble fiber as compare to any other grain. The soluble fiber in oats comprises of beta glucan, a class of polysaccharide  having mixed linkages. The percentages of beta glucan in various products of whole oats are: oat bran >5.5-23%, rolled oats and oat flour  about 4 %. FDA in 1998 approved to claim food products containing 3g of soluble fiber from oats can be labeled as foods reducing risk of  heart disease.⁴⁹ The major bioactive components in oats responsible for lipid lowering seem to be beta glucan as reported by various  trials discussed in table 6.

Table 6: Interventional trial data on lipid  lowering effects of oats Click here to View table

To  Summarize

The results from these studies (50-56.) suggest that oats beta glucan is efficacious in significantly improving lipid profile as it was able to  reduce TC and LDL-c in normal as well as hypercholesterolemic subjects significantly (p=<  0.05). Its intervention also significantly  increased HDL levels (Villasmil R et al). It was also effective in decreasing LDL: HDL and TC: HDL ratios from the baseline significantly.  Queenen et al also found that oats beta glucan is a most fermentable fiber and produces the highest levels of SCFA butyrate compared to  inulin and guar gum in vivo. Oat bran also proven to be beneficial in9; premenopausal women as it increased HDL-c levels and reduced  LDL and TC levels. Oats was also able to reduce classical CVD risk marker i.e. systolic blood pressure (SBP) significantly (p=0.026) in the trial conducted by Saltzman E et al. thus daily incorporation of 25-150g/d of oats or 2.5-6.0g of beta glucan is effective in the treatment of mild-moderate dyslipidemia.

Psyllium

Psyllium seed husk also known as isabgol are the seeds of plant Plantago otava. They are indigestible by the human intestine, thus helps  in holding large amounts of water and making the stools bulky and soft for easy defecation; therefore they are used in the treatment of  constipation, Irritable bowel syndrome, diarrhea etc. As early as in 1998, the FDA already have approved a healthy claim on daily  incorporation of 3-12grams of psyllium along with a low fat diet may reduce risk of heart disease.⁵⁷ The hypolipidemic effects of psyllium  mucilage have been discussed by various epidemiological studies in table 7.

Table 7: Interventional trial data on lipid  lowering effects of psyllium Click here to View table

To  Summarize

Various human clinical trials on psyllium^58-62 suggest that this mucilage enriched food item is effective in lowering total cholesterol,  LDL-c, triglycerides and improving the concentrations of good cholesterol HDL-c in the serum of normal and hypercholesterolemic  subjects. Also the effects were more prominent in postmenopausal women as concluded by Ganji V et al. Psyllium was also effective in  lowering Apo B 100: ApoA1, TC: HDL. LDL: HDL and also increasing conc of Apo A1; the apoprotein of HDL; thus reducing the primary  and secondary ASCVD risk factors. Moreyra A, et al also concluded that 15g/d of psyllium intervention was as effective in lowering  cholesterol as 20 mg of simvastatin alone. Therefore, psyllium 5-15g/d is an effective adjunct therapy and may provide an alternative to  drug therapy for mild-moderate hypercholesterolemic individuals.

Conclusion

Dyslipidemia and ASCVD morbidity is increasing at an alarming rate nationwide and thus it becomes essential to prevent or treat  dyslipidemia to regress the associated metabolic derangements. Fortunately today we can combat this situation initially through diet and  physical activity before switching on to cholesterol lowering drug therapy. Merely by including the discussed hypolipidemic dietary agents in the required dosage as inferred from researches and recommendations i.e. oats 45-150g/d or beta glucan 2.5-6g/g; 20-25g of soy protein or 30-150mg of isoflavones; flaxseeds 20-50g of whole or partially defatted respectively; psyllium 5-15g per day along with a low  fat NCEP followed diet and recommended physical exercise are significantly effective in improving serum lipid profile. The discussed  food items may be effective in preventing, reversing or managing most prevalent chronic conditions as mentioned earlier, and hence may  be claimed as to be “first line therapy” in dyslipidemia management. They can simply be incorporated in ones daily diet as they are less  expensive, readily available, relatively have no side effects, practical and effective in recommended low dosages. They are proven to be  more effective in mild-moderate hyperlipidemics like postmenopausal women who are hesitant to follow a life-long drug therapy for  improving their mildly deranged lipid profile. This review attempts to not only enlist the effects, possible mechanism and bioactive  components of the food item but also to quantify the same to have a desired effect on individual lipid profile.

Limitations

While the majority of the published intervention studies suggest a lipid lowering effects of moderate doses of these food items administration, question remains about the consistency, efficacy, safety and duration of these effects. Future studies will need to clarify  the lipid effects in more varied populations (men and premenopausal women).

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