272 Personalized Nutrition as Medical Therapy for High-Risk Diseases

dietary intake of favonols from various sources like fruits, vegetables and tea are
associated with a reduced risk of CHD mortality (Huxley and Neil 2003). In addi-
tion, several studies of fatal CHD were evaluated, with intake of favonoid classes,
favone and favonol which showed that combined consumption of both favone and
favonol lowered the risk of fatal CHD (Hertog, Feskens et al. 1993; Hertog, Feskens
et al. 1997). A recent 30 days’ study conducted among hypercholesterolemia patients
when administered with bergamot (C. bergamia Risso & Poiteau) fruit extract, which
is rich in naringin, neoeriocitrin, neohesperidin, melitidin and brutieridin revealed
a dose-dependent reduction of total and LDL cholesterol levels with subsequent
increase in HDL-cholesterol levels (Mollace, Sacco et al. 2011). Thus, favonoids by
virtue of their hypocholesterolemic property may be relevant in the prevention of
various heart diseases including CHD.

10.8.15 GARLIC
For a long time, garlic has been the subject of clinical trials in lowering choles-
terol levels in humans. Earlier meta-analysis trials suggested a signifcant reduction
in serum total cholesterol levels in garlic supplemented participants (Warshafsky,
Kamer et al. 1993; Silagy and Neil 1994; Stevinson, Pittler et al. 2000). Recently
a study conducted by Sobenin, Andrianova et al. (2008) showed that garlic tablets
(Allicor—comprising 600 mg of garlic) moderately altered the lipid levels such as:
7.6% decrease in cholesterol; 11.7% decrease in LDL cholesterol and a substantial
increase in 11.5% HDL cholesterol. Thus, garlic displays potent benefcial effects
due to its inherent hypocholesterolemic properties.

10.9 HEART-HEALTHY DIETS

The National Heart, Lung, and Blood Institute (NHLBI, NIH (US)) includes the fol-
lowing under a heart-healthy diet:

• Fat-free or low-fat dairy products.

• Fish rich in omega-3 fatty acids, such as salmon, tuna and trout.
• Fruit, such as apples, bananas, oranges, pears and prunes.
• Legumes, such as kidney beans, lentils, chickpeas, black-eyed peas and
lima beans.
• Vegetables, mainly broccoli, cabbage and carrots.
• Whole-grains, such as oatmeal, brown rice and corn tortillas.
• Monounsaturated and polyunsaturated fats-containing products:
• Avocados.
• Corn, sunfower, and soybean oils.
• Nuts and seeds, such as walnuts.
• Olive, canola, peanut, saffower and sesame oils.
• Peanut butter.
• Salmon and trout.
• Tofu.
Personalized Nutrition in Hypercholesterolemia 273

10.10 HEART-UNHEALTHY DIETS

The following are heart-unhealthy diets that are to be avoided (NHLBI, NIH (US)).

• Excessive red meat.

• Palm and coconut oils.
• Sugary foods and beverages.
• Saturated fat.
• Trans-fat (trans-fatty acids).

10.11 PUBLIC HEALTH RECOMMENDATIONS

FOR NUTRITION AND LIFESTYLE
For the purpose of prevention or as a part of treatment for diseases, several opinion
leader organizations have recommended and published lifestyle medicine, consist-
ing primarily of diet and physical activity. The US Department of Agriculture and
the US Department of Health and Human Services published an extensive guideline
on the healthy dietary pattern for the American population in the year 2010 (2010).
The lifestyle medicine recommendations for general populations are illustrated in
Figure 10.3.

10.12 THERAPEUTIC MEASURES

Despite outstanding advancement in the area of the management of CVDs, signif-
cant challenges are warranted for the better outcome of the treatment of CVD.

10.12.1 ANTIOXIDANT THERAPY

A variety of antioxidants available from several biological and chemical origin can
be involved in the therapeutic management of CVD. Dietary antioxidants that help
in the management of CVD are mainly comprised of polyphenols, which include the
favonoids and phenolic acid. Additionally, other antioxidants that are present in the
diet include vitamin E, carotenes, vitamin C, lycopene, etc.

10.12.1.1 Coenzyme Q 10 (CoQ10)

CoQ10, an antioxidant, plays a vital role in preventing the oxidation of cell mem-
branes, LDL cholesterol, HDL cholesterol and various other blood components
(Crane 2001). CoQ10 acts as an inhibitor of lipid peroxidation at the initial as well
as intermediate steps, thus validating it as an essential antioxidant (Ernster and
Forsmark-Andree 1993). FDA has approved CoQ10 as a supplement for the manage-
ment of CVD. LiQ10® (syrup) and Q-Gel® and Q-Nol® (soft gelatin capsules) are
among the foremost commercially available formulations of CoQ10 (Swarnakar, Jain
et al. 2011). Daily consumption of CoQ10 (150 mg/d) is documented to decrease oxi-
dative stress, infammatory markers (IL-6) and improve resistance against oxidation
of LDL cholesterol (Witting, Pettersson et al. 2000; Lee, Huang et al. 2012).
274 Personalized Nutrition as Medical Therapy for High-Risk Diseases

FIGURE 10.3 Lifestyle medicine recommendations. (US Department of Agriculture and

US Department of Health and Human Services 2010.)

10.12.1.2 Carotenoids
Carotenoids are dietary antioxidants that play a major role in controlling CVD. Since
their carotenoids are not synthesized in the human body they are obtained from
diet or other supplements. Commercially there are various carotenoid supplements
available for controlling CVD which include AstaSana™ (Astaxanthin), CaroCare®
(beta carotene) and Redivivo® (lycopene). Dietary intake of beta carotene has also
been documented to be of beneft in different CVD including atherosclerosis and
hypertension (Gammone, Riccioni et al. 2015). Beta carotene acts through a dif-
ferent mechanism and prevents lipid peroxidation enhances lymphocyte prolifera-
tion and modulates vascular nitric oxide bioavailability (Jialal, Norkus et al. 1991;
Robbins and Topol 2002). Lycopene, a red pigment present in fruits and vegetables
also possess antioxidant properties and plays a role in the management of various
CVD (Muller, Caris-Veyrat et al. 2016).
Personalized Nutrition in Hypercholesterolemia 275

10.12.1.3 Polyphenols
Polyphenols act through diverse mechanisms and prevent CVDs. It is reported to
inhibit ROS and reactive nitrogen species by directly scavenging peroxynitrite,
hydroxyl radicals, superoxide anion and nitric oxide (Tangney and Rasmussen 2013).
Among the various polyphenols available, resveratrol has shown a substantial role in
the management of various CVDs including atherosclerosis, hypertension, ischemic
heart disease, stroke, arrhythmia and chemotherapy-induced cardiotoxicity, heart
failure and diabetic cardiomyopathy.

10.12.2 MEDICINES CURRENTLY USED TO TREAT CVDS

• Anticoagulants.
• Aspirin.
• Angiotensin-converting enzyme (ACE) inhibitors.
• Beta-blockers.
• Calcium channel blockers.
• Nitroglycerin.
• Glycoprotein IIb-IIIa.
• Statins.
• Fish oil and other supplements high in omega-3 fatty acids.

10.12.3 CHOLESTEROL-LOWERING DRUGS

Medicines can help lower cholesterol levels but it can’t guarantee to cure it, so it
is recommended to continue taking medicine to keep cholesterol levels in the rec-
ommended stage. Five major types of cholesterol-lowering medicines commercially
available include:

• Statins: reported to lower LDL cholesterol levels.

• Bile acid sequestrants which also help lower LDL cholesterol.
• Nicotinic acid documented to lower LDL cholesterol and triglycerides and
raise HDL cholesterol levels.
• Fibrates lower triglycerides, and also can raise HDL cholesterol levels.
• Ezetimibe lowers LDL cholesterol levels.

10.12.3.1 Antiplatelets
Antiplatelets help to inhibit the functions of platelets in the blood by reducing the
bloodclotting process thus preventing the platelets from sticking to blood vessel
walls. They are also known as anti-aggregants.
At present two types of antiplatelet drugs have been approved:

• Acetylsalicylic acid (ASA): People with CVD are usually recommended to

take one 100 mg tablet per day.
• Clopidogrel: Frequently used by patients who can’t tolerate ASA. One tab-
let of 75 mg is taken per day.
276 Personalized Nutrition as Medical Therapy for High-Risk Diseases

Studies report that ASA prevents heart attacks or strokes in about fve to ten out
of 100 people who have CHD. Thus, people with CHD, with regular ASA intake
can be prevented from major complications like heart attacks or strokes. In addi-
tion, the drug clopidogrel is also known to function equally with ASA in preventing
complications.

10.12.3.2 Statins
Statins are one of the most common medicines used to lower cholesterol levels in
the blood. Recently they have been thought to protect the blood vessel walls by
inhibiting infammation. The approved statins are simvastatin, atorvastatin, fuvas-
tatin, lovastatin and pravastatin. Among them, simvastatin and atorvastatin are most
commonly used, taken at the dose of 40 mg per day and 10 mg per day respectively
(Mills, Wu et al. 2011). Studies show that people with coronary artery disease who
take statins regularly over a period of time have reduced the risk of coronary artery
disease complications and statins are generally welltolerated by the patients (Naci,
Brugts et al. 2013).

10.12.3.3 Beta-Blockers
Beta-blockers are mainly recommended for people who have coronary artery dis-
ease as well as high blood pressure or heart failure (Ko, Hebert et al. 2004). Besides,
beta-blockers also help in relieving angina. Various types of beta-blockers are avail-
able. Among them, bisoprolol and metoprolol are the ones most commonly used.
Bisoprolol and metoprolol are usually used at the dose of 2.5 to 5 mg per day and 50
to 100 mg per day respectively.

10.12.3.4 ACE Inhibitors and Angiotensin II Antagonists

ACE inhibitors and angiotensin II antagonists, also known as sartans are consid-
ered to be blood pressure-lowering drugs. ACE inhibitors and angiotensin II antago-
nists function by dilating (widening) the blood vessels, thereby lowering the blood
pressure.

10.12.4 CONVENTIONAL THERAPEUTIC STRATEGIES

A varied range of conventional therapeutic strategies has been developed for the
treatment of CVDs including gene delivery or therapy, cell transplantation and stem
cell therapy, tissue factor inhibitors, micro RNSs and or other small molecules.

10.12.4.1 Gene Delivery or Therapy

The evolution of vector technology has emerged as a signifcant technique for under-
standing the advanced molecular mechanisms underlying CVDs. Gene therapy
appears to be an attractive alternative to current pharmacological therapies which
may be considered benefcial in the treatment of CVDs (Katz, Fargnoli et al. 2013).
Moreover, the recent advancement in recombinant technology such as gene transfer
has stimulated some hope that this technique can be used to improve the practice
of cardiovascular medicine. In animal models, gene therapy coding for antioxi-
dants, heat shock proteins (HSPs), mitogen-activated protein kinase (MAPK) and
Personalized Nutrition in Hypercholesterolemia 277

numerous other proteins have revealed signifcant cardioprotection (Guellich, Mehel

et al. 2014).

10.12.4.2 Cell Transplantation and Stem Cell Therapy

Stem cell-based therapies have emerged as a novel promising therapeutic approach
for patients with different heart diseases. Studies on cell-based therapies suggest an
improvement in cardiac function and regeneration of the damaged tissue (Segers and
Lee 2008).
Further, the therapeutic strategies underlying tissue factor inhibitors, micro RNAs
and other small molecules are warranted to be benefcial for the treatment of CVDs.
In addition, the potential technology utilizing nanoscale dimension materials can
play a role in bridging the gap between molecular and cellular interactions, and has
the potential to revolutionize medicine. Moreover nanomedicine, when compared to
traditional medicine offers treatment as effectively as possible with negligible side
effects, and an enhanced clinical result (Singh, Garg et al. 2016). Among the conven-
tional therapeutic measures, gene therapy plays a promising role in the treatment and
prevention of CVDs (Perk, De Backer et al. 2012).

10.13 CONCLUSION
CHD persists as the leading cause of death worldwide and hypercholesterolemia
remains the major risk factor for the development of CHD. Early detection of hyper-
cholesterolemia can help prevent premature CHD as well as CVD. Diet therapy plays
a vital role in the treatment of hypercholesterolemia. Maintenance of a personal-
ized healthy diet containing diverse foods is recommended for lowering the risk of
CVD. The diet should include a variety of fruits, vegetables, whole-grains, whole
wheat bread, legumes, and high-fber low-salt food items. Vegetable oils, mainly
olive and canola oils, excluding palm and coconut oils, are preferable to animal fats.
Moreover, there are certain other compounds that may confer benefts for CVD such
as nuts, almonds, avocado and tahini, low-fat dairy products, green tea and two to
three servings of fatty fsh per week. The Mediterranean diet has been documented
to reduce cardiovascular morbidity and mortality in both primary and secondary
prevention. Additionally, other dietary patterns that could be suggested are a low-
fat diet for people reported with cardiovascular risk, the DASH diet for people with
hypertension, and lowcarbohydrate diets for overweight people or those suffering
from metabolic syndrome.

ABBREVIATIONS
ACE: Angiotensin-converting enzyme
ALA: Alpha Lipoic acid
CHD: Coronary heart disease
CoQ10: Coenzyme Q10
CVD: Cardiovascular disease
DASH: Dietary Approach to Stop Hypertension
EPA: Eicosapentaenoic acid
278 Personalized Nutrition as Medical Therapy for High-Risk Diseases

FDA: Food and Drug Administration

HDL: High-density lipoprotein
HSP: Heat shock protein
LDL: Low-density lipoprotein
NHLBI: National Heart, Lung, and Blood Institute

REFERENCES
Andrade, J., A. Mohamed, et al. (2009). “Ancel keys and the lipid hypothesis: from early
breakthroughs to current management of dyslipidemia.” BC Med J 51(2): 66–72.
Appel, L.J., T. J. Moore, et al. (1997). “A clinical trial of the effects of dietary patterns
on blood pressure. DASH collaborative research group.” N Engl J Med 336(16):
1117–1124.
Bazzano, L. A., M. K. Serdula, et al. (2003). “Dietary intake of fruits and vegetables and risk
of cardiovascular disease.” Curr Atheroscler Rep 5(6): 492–499.
Belahsen, R. (2014). “Nutrition transition and food sustainability.” Proc Nutr Soc 73(3):
385–388.
Benjamin, E. J., M. J. Blaha, et al. (2017). “Heart disease and stroke statistics-2017 update: a
report from the American Heart Association.” Circulation 135(10): e146–e603.
Brown, L., B. Rosner, et al. (1999). “Cholesterol-lowering effects of dietary fber: a meta-
analysis.” Am J Clin Nutr 69(1): 30–42.
Brufau, G., J. Boatella, et al. (2006). “Nuts: source of energy and macronutrients.” Br J Nutr
96(2 Suppl): S24–S28.
Carpenter, K. J. (2003). “A short history of nutritional science: part 1 (1785–1885).” J Nutr
133(3): 638–645.
Chan, L. and E. Boerwinkle (1994). “Gene-environment interactions and gene therapy in
atherosclerosis.” Cardiol Rev 2(3): 130–137.
Chen, Z.-Y., K. Y. Ma, et al. (2011). “Role and classifcation of cholesterol-lowering functional
foods.” J Funct Foods 3(2): 61–69.
Crane, F. L. (2001). “Biochemical functions of coenzyme Q10.” J Am Coll Nutr 20(6):
591–598.
Dauchet, L., P. Amouyel, et al. (2005). “Fruit and vegetable consumption and risk of stroke: a
meta-analysis of cohort studies.” Neurology 65(8): 1193–1197.
de Koning Gans, J. M., C. S. Uiterwaal, et al. (2010). “Tea and coffee consumption and car-
diovascular morbidity and mortality.” Arterioscler Thromb Vasc Biol 30(8): 1665–1671.
Deka, A. and J. A. Vita (2011). “Tea and cardiovascular disease.” Pharmacol Res 64(2):
136–145.
Eilat-Adar, S., T. Sinai, et al. (2013). “Nutritional recommendations for cardiovascular dis-
ease prevention.” Nutrients 5(9): 3646–3683.
Elwood, P. C., J. E. Pickering, et al. (2010). “The consumption of milk and dairy foods and
the incidence of vascular disease and diabetes: an overview of the evidence.” Lipids
45(10): 925–939.
Ernster, L. and P. Forsmark-Andree (1993). “Ubiquinol: an endogenous antioxidant in aerobic
organisms.” Clin Investig 71(8 Suppl): S60–S65.
Escurriol, V., M. Cofan, et al. (2009). “Serum sterol responses to increasing plant sterol intake
from natural foods in the Mediterranean diet.” Eur J Nutr 48(6): 373–382.
Food and Drug Administration, HHS (2008). “Food labeling: health claims; soluble fber
from certain foods and risk of coronary heart disease. Interim fnal rule.” Fed Regist
73(37): 9938–9947.
Gammone, M. A., G. Riccioni, et al. (2015). “Carotenoids: potential allies of cardiovascular
health?” Food Nutr Res 59: 26762.