**4.5 Effect of ginger on lipid profile**

The greatest cause of atherosclerosis is characterized by altered blood lipid values and consequently CVD. In addition, the factors previously mentioned, such as overweight/obesity and high blood glucose values, are factors that will have a greater effect on this pathology.

Impaired blood lipid values are the major cause of CVD. In a recent systematic review and meta-analysis of clinical trials in 2018, it was concluded that ginger has a favorable effect in reducing triglycerides and LDL cholesterol, without significant reductions in total cholesterol. However, doses lower than 2 g/day of dairy ginger powder seem to be more effective in lowering both triglycerides and total cholesterol [83]. Since it is a safe and inexpensive supplement, it could be used to improve the lipid profile of subjects and thus prevent CVD.

*Ginger in the Prevention of Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.103970*

Clinical studies have been conducted to evaluate the effect of ginger supplementation on the lipid profile of different populations. Doses of up to 1.8 g/day have been shown to significantly reduce triglyceride, total and LDL cholesterol levels compared with placebo in obese patients treated with metformin (**Table 2**) [85].

Significant lowering effect of ginger compared with placebo has also been observed in [86, 87]. However, other studies failed to observe a positive effect, and ginger supplementation exerted no effect on blood lipid profiles and body composition [88] and no significant differences in cholesterol lipoproteins profile between ginger and placebo [89]. In some cases, the results are inconsistent, with significant differences in some markers as LDL/HDL ratio after ginger intake and no changes on mean levels of total cholesterol or triglycerides [90], or reductions in levels of serum triglycerides and LDL with no effects on total cholesterol or high-density lipoprotein (HDL) [91].

Levels of apolipoprotein B and apolipoprotein B/apolipoprotein A-I ratio reduced and apolipoprotein A1 increased after ginger supplementation (2 g/day) for 12 weeks [92]. The overexpression of ApoA1 could explain the increases observed in HDL levels in some trials.


#### **Table 2.**

*Summary of the effect of ginger supplementation on the lipid profile in different clinical trials and populations.*

Discrepancies in the results could be due to the different characteristics of the populations studied, stage of the disease, pharmacological treatments, format of ginger administered.

Meta-analysis studies have concluded that ginger significantly increases HDL levels and reduces plasma levels of triglycerides and total cholesterol, with different extent depending on the clinical condition (hyperlipidemia and T2DM) [93, 94]. The analysis conducted by Pourmasoumi et al. [83] revealed a better effect of total cholesterol and triglycerides with doses < 2 g/day and a maximum of 50 days of supplementation.

Among the different mechanisms of action attributed to ginger components is the inhibition of intestinal lipase enzymes, thus avoiding fat hydrolysis and absorption and the increase in plasma levels of triglycerides. In case of cholesterol, its decrease in plasma concentrations has been related to an inhibition in cellular cholesterol synthesis and an increase of hepatic enzyme activity of cholesterol 7 α-hydrozylase CYP7A1a, implicated in the conversion of cholesterol into bile acids for its clearance by fecal excretion [95]. Ginger is implicated in the inhibition of expression of adipogenesis and lipogenesis genes as PPAR γ and carbohydrate-responsive element-binding protein (ChREBP) gene expression in the liver [66]. ChREBP reduced expression further decreases the expression of glucogenic and lipogenic enzymes (as fatty acid synthase, steatoryl-CoA-desaturase-1, acetyl-CoA carboxylase 1, among others [95].

#### **4.6 Effect of ginger on blood pressure**

It is well known that healthy diet and lifestyle can control blood pressure and endothelial dysfunction. Inflammation associated with cardiovascular events contributes to hypertension by affecting the renin-angiotensin system [96]. Elevated blood pressure (BP) has also been known to be a strong risk factor cardiovascular [97].

The compounds in ginger responsible for its antihypertensive effect are 6-shogaol and 9-gingerol. These compounds reduce cholesterol and LDL levels, inhibit atheroma plaque formation, and increase vessel elasticity. They also reduce the release of inflammatory mediators responsible for endothelial dysfunction by decreasing intercellular adhesion molecule 1 (ICAM-1) levels [98]. Several authors [99] show the antihypertensive effect of ginger in volunteers with mean ≤ 50 years, with ginger doses ≥ 3 g/day, and during an intervention period ≤ 8 weeks. This effect could be due to its antioxidant activity.

A systematic review with 345 participants from six clinical trials showed that ginger consumption has favorable effects on blood pressure. These authors observed that increasing ginger intake decreased the probability of ischemic heart disease and hypertension [100]. This result coincides with that observed in a clinical trial with 4628 participants in which the efficacy of ginger in coronary heart disease and as an antihypertensive was observed [101].

#### **4.7 Antiplatelet aggregation activity of ginger**

Platelet aggregation and activation play an important role in developing thrombosis and atherosclerosis. Numerous nutrients and bioactive compounds have a potential role in platelet function and may decrease cardiovascular risk. These include berries, caffeine, chocolate, garlic, ginger, the omega-3 polyunsaturated fatty acids (PUFA), onion, and tomato [102].

ZGR is a compound (phenolic alkanose) found in *Zingiber officinale*. It exhibits anti-apoptotic, anti-inflammatory, and protective properties against cardiovascular *Ginger in the Prevention of Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.103970*

events such as myocardial infarction. Several authors have observed its anticoagulant and antithrombotic properties. This compound inhibits platelet aggregation induced by adenosine diphosphate (ADP), and U46619 (not thrombin), Tx2 inhibitor, inhibits the catalytic activity of factor Xa (FXa) toward its substrate S-2222 in a non-competitive inhibition model, reduces P-selectin and PAC-1 expressions in platelets, and reduces activated partial thromboplastin time [103].

Several authors [104] observed that consumption of a 10 g dose of powdered ginger after 4 hours significantly reduced ADP- and adrenaline-induced platelet aggregation. McEwen analyzed the *in vitro* antiplatelet activity of ginger and showed that gingerol, its analogues (1 and 5), paradol and shogaol, exhibited antiplatelet activity with IC50 values between 5 and 7 μM [18]. To be noted, aspirin inhibitory effect shows IC50 values of 20 ± 11 μM, and paradol shows IC50 values of 4 ± 1 μM.

Ginger has a vascular protective effect mediated by different mechanisms such as reduction of inflammation and oxidative stress, increase of nitric oxide synthesis, which is a potent vasodilator, the promotion of autophagy, and inhibition of vascular smooth muscle cell [105].

Comparing different ginger compounds, several investigators have shown that 6-gingerol and 6-shogaol showed the most potent bioactivity against cholesterol (Chol), arachidonic acid (AA), thrombin, and PAF-induced platelet aggregation [106]. The 6-paradol, 10-dehydrogingerol, 10-gingerol showed the most significant inhibition of AA-induced aggregation [107].

Nurtjahja-Tjendraputra et al. observed that 8-paradol is the most effective anticoagulant, being a COX-1 inhibitor [108].

Thomson et al. fed rats with ginger aqueous extract and observed a decrease in triglyceride, thromboxane-B2 cholesterol and PGE2 levels, and in adenosine deaminase (ADA) activity of plaques, together with an increase in adenosine levels. In this way, it favors vasodilatation, reducing the complications of hypertension and preventing from unnecessary platelet aggregation [108].
