Intermittent fasting is a hot topic in the diet and nutrition world. There are many books, blogs, celebrities and even apps touting the many health benefits of this pattern of energy consumption. The question is whether there is sufficient clinical research to supports these claims. Intermittent fasting has been a part of religious practices for centuries. Christian, Muslim, Buddhist, Hindu and Jewish populations all perform intermittent fasting at different times throughout the year. Clinical studies on intermittent fasting are still quite limited and what we do know comes mostly from: animal studies, a handful of human trials with small sample
Metabolic syndrome refers to the “perfect storm” of hypertension, dyslipidemia, poor blood glucose regulation, and the presence of intra-abdominal adipose accumulation. Having metabolic syndrome increases the likelihood of developing atherosclerosis and cardiovascular disease (CVD), in addition to Type 2 diabetes.
Prevention and treatment of each of these disorders includes dietary and lifestyle changes, including decreasing intake of sugar and simple carbohydrates, and regular physical activity. However, many individuals find these changes too difficult, or may need additional support if areas such as blood pressure, glucose, insulin or cholesterol aren’t coming into normal range within a reasonable amount of time.
Conventional treatments often cause side effects that dissuade patients from starting or continuing treatment. Dietary supplementation offers a treatment option with less side effects and, in many cases, equal clinical outcomes.
Most CVD-related deaths are the result of atherosclerosis which can lead to myocardial infarct (MI), pulmonary embolism or stroke. Therefore when treating or preventing CVDs, it’s important to address LDL cholesterol levels, but also oxidative stress, systemic inflammation, while making cardiac function efficient and preventing myocardial damage.
Managing Cholesterol and LDL Oxidation
Red Yeast Rice Extract
Statin drugs act as HMG-CoA reductase inhibitors, preventing the production of cholesterol in the liver. Red yeast rice (RYR) extracts consist of the Monascus purpureus yeast species which is cultured on rice. Cultivation results in the production of monacolins which act like statins by inhibiting HMG-CoA reductase. Monocolin K, specifically, is identical to the drug known as lovastatin, but with higher bioavailability in RYR extracts.1
Many studies have shown that 10mg of monocolin K from RYR can normalize and sustain LDL levels.2 A meta-analysis of 13 randomized, placebo-controlled trials with a total of 804 patients, showed that RYR was able to significantly decrease serum total cholesterol (TC), triglycerides (TG), and LDL cholesterol compared to placebo.3
Olive Oil and Fish Oil
Polyphenol compounds from olive extracts act as cardiovascular antioxidants. Specifically, the polyphenol hydroxytyrosol protects against LDL oxidation, while olive oil has been shown to efficiently reduce blood pressure in hypertension.4
In a double-blind randomized, placebo-controlled trial, 50 unmedicated patients with metabolic syndrome were given 10mg hydroxytyrosol with 10 mg of monokolins from RYR. Combination treatment led to a 24% decrease in LDL concentration, with a 1% increase in LDL in the placebo group.2 Treatment also resulted in 20% lower oxidized-LDL and a 6% reduction in aboB compared to increases in LDL and apoB in the placebo group by 5% and 6%, respectively. Blood pressure also decreased in the treatment group on average by 10/7 mmHg.
One group of researchers calculated the fraction and absorption of hydroxytyrosol in olive oil and concluded that individuals in Mediterranean countries consume approximately 30-50 g of olive oil daily, resulting in 4-9 mg of olive oil phenols. Considering that the above study used between 9-10 mg of hydroxytyrosol daily, it’s possible to obtain a similar amount from the diet, assuming a Mediterranean-style diet.
Bergamot is a citrus fruit with high contents of flavonoids such as neoeriocitrin, neohesperidin and naringin. Bergamot’s flavonoid content is responsible for its anti-inflammatory and antioxidant properties, especially on human vessel endothelial cells.5 Bergamot extracts modulate NF-kB and protect against vascular damage.5
In addition to its anti-atherosclerotic effects, bergamot flavonoids such as naringin can also improve insulin sensitivity and glucose tolerance. In one study, 237 patients with hyperlipidemia (with or without hyperglycaemia) were given a bergamot extract daily for 30 days, which led to reductions in total and LDL cholesterol levels as well as triglycerides (TG), increased HDL, and significantly decreased blood glucose.6
In another clinical trial, 80 patients with moderate hypercholesterolemia were given a bergamot-derived extract containing 150 mg flavonoids (16% neoeriocitrin, 47% neohesperidin and 37% naringin).7 After six months of treatment, patients had significantly reduced TC (-0.8 mmol/L), TG (-0.3 mmol/L), and LDL (- 0.9 mmol/L) concentrations, and a significant increase in HDL cholesterol by about 0.1 mmol/L.
Bergamot’s efficacy is similar to statin medications, but interestingly, when given together, bergamot actually enhanced the lipid-improving effect of rosuvastatin.8
Vitamin E, commonly supplemented in the form of alpha-tocopherol, is a fat-soluble vitamer well known for its antioxidant properties. Vitamin Einhibits LDL oxidation and decreases foam cell formation by suppressing expression of NF-kB and P-selectin. Vitamin E also reduces production of adhesion molecules.
Tocotrienols, in addition to tocopherols, have been found to lower CVD risk by regulating cholesterol metabolism. As part of the Cambridge Heart Antioxidant Study, treatment with
alpha-tocopherol decreased the risk of MI in patients with coronary atherosclerosis.9
Studies suggest that supplementation should include all eight forms of E-vitamins. Research has shown that by just providing exclusively one form, i.e. alpha-tocopherol, it can deplete other important forms such as gamma-tocopherol. While alpha is important, depletion of other vitamers is undesirable. Gamma-tocopherol is important for inhibiting protein kinase C activity and reducing smooth muscle cell proliferation. Both alpha and gamma reduce platelet aggregation and thrombosis in animal models but gamma has a stronger effect on lipid peroxidation and is also associated with improved endothelial cell nitric oxide synthesis.10
Resveratrol and Carnitine Post-MI
Resveratrol, an antioxidant, anti-inflammatory and sirtuin activator, decreases vascular inflammation via COX-1 inhibition. Resveratrol also protects the vascular system by increasing NO production via increasing endothelial expression of NO synthase.11
In a three-month clinical trial, patients were treated with either 10mg resveratrol daily or placebo in addition to their standard medication post-MI.12 Those given resveratrol had decreased LDL, improved endothelial and systolic function and decreased platelet aggregation. Pre-treatment with resveratrol protects myocardial tissue by decreasing infarct size and reduce arrhythmias.
Carnitine supports myocardial energy by transporting fatty acids into the mitochondria. Researchers suggest that L-carnitine supplementation may protect against cardiac necrosis within 28 days post-MI.13 In this study, patients with suspected MI were randomized to 2 g of carnitine daily x 28 days. The group given carnitine had significantly decreased infarct sizes compared to placebo. LV enlargement and total arrhythmias were also significantly less in the carnitine group.
Taurine and Magnesium
Taurine is an endogenously produced amino acid from methionine. It has antioxidant and anti-inflammatory effects, can regulate blood pressure via vasorelaxation, and is cardio-protective against cardiac injury.14 Magnesium on the other hand is well known for its vasorelaxation effects and is frequently used in cases of elevated blood pressure. However, supplementation is also associated with reductions in insulin resistance and arrhythmias.15
Taurine decreases the risk of atherosclerosis, and when given with magnesium, reduces oxidative stress, stabilizes platelets and improves endothelial function.14,15
In an animal model of MI, taurine mitigated the diastolic dysfunction caused by MI injury, preventing thickening of the left ventricular (LV) posterior wall, the interventricular septum and the mass of the LV induced by MI.16
In cases of congestive heart failure (CHF), taurine can reduce symptoms such as shortness of breath with exertion, and edema.14 One study found that supplementing CHF patients with 3 g taurine daily for six weeks significantly improved LV systolic function.17 In another study, 1500 mg daily for two weeks in patients with CHF led to improved exercise capacity.18
Natto is a fermented soybean product, consumed by humans for thousands of years but the active protein nattokinase (NK) is relatively new to human trials. NK’s fibrinolytic enzymatic actions have been found to directly breakdown blood clots in animal models with recent human trials showing promise.
In an animal model of thrombosis, NK showed complete lysis of the clot within five hours at a dose of 8,000 FU.19 In a similar study, rat models with induced thrombi in the common carotid artery showed an 88% reduction in thrombus within six hours at a dose of 2,836 FU with NK showing four times more potent activity than plasmin.20
NK appears to activate multiple clot-dissolving factors including urokinase and tissue plasminogen activator (tPA).21 NK also blocks clot forming factors such as thromboxane.
Coenzyme Q10 is a compound that can be used across all stages of CVD and metabolic disease, but also in progressed cases of CHF. CoQ10 is known for its role in the electron transport chain to increase cellular energy production, but it also acts as an antioxidant against lipid peroxidation.
Meta-analyses have reported that CoQ10 can significantly improve cardiac output, stroke volume and ejection fraction.22 It also enhances cellular energy of cardiomyocytes and oxygen utilization.23 Additionally, CoQ10 can modulate the effects of angiotensin and aldosterone thereby regulating blood pressure. One meta-analysis suggested that CoQ10 could decrease elevated systolic blood pressure by about 11 mmHg after 12 weeks of treatment.23
It’s other cardioprotective effects are illustrated by decreases in plasma fibronectin, thromboxane B2 and in reduction of platelet size.23
In a small clinical study, 26 patients with essential arterial hypertension were treated with 100 mg CoQ10 for 10 weeks. At the end of the treatment period, systolic and diastolic blood pressures significantly decreased by 17 mmHg and 12 mmHg, respectively (P<0.0001)24. As well, serum TC significantly decreased and serum HDL significantly increased after treatment.
Dietary and Lifestyle Treatments
There are many modifiable dietary and lifestyle factors that can contribute to the progression of CVD by increasing inflammation, oxidative stress, and sympathetic activation. Each of these factors can lead to obesity, diabetes, and dyslipidemia. It’s recommended to address the following in addition to therapeutic prescribing:
- Limit excess caloric intake and discuss healthy food choices, such as aiming for a Mediterranean-like or plant-based diet
- Limit alcohol intake
- Prevent sedentary lifestyle and participate in regular physical activity
- Manage mental and emotional stress
- Screen for sleep apnea
Exercise recommendations include:
- An intensity of 70% maximum heart rate
- Include resistance training such as the use of elastic resistance bands, weights, and the use of body weight exercises for resistance against gravity.
- Duration of exercise should be at least 30 minutes, but shorter and/or modified for frail patients
- Always include a warm-up and cool-down
- Patients should engage in exercise daily up to five days per week
Individuals with metabolic syndrome (or even one of its components) have both pharmaceutical and food-based treatment options that can be equally beneficial. Even more so, options of nutrient supplementation may save individuals from experiencing harsh side effects of pharmaceuticals that could deter patients from treatment.
- Xue T, Tao L, Wu S, et al. (2017). Red yeast rice induces less muscle fatigue symptom than simvastatin in dyslipidemic patients: a single center randomized pilot trial. BMC Cardiovasc Disord. 17(1): 127
- Verhoeven, V, Van der Auwera A, Van Gaal L, et al. (2015) Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome?: A double blind, placebo controlled randomized trial. BMC Complement Altern Med. 15: 52
- Li Y, Jiang L, Jia Z, et al. (2014). A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 9(6): e98611
- Peyrol J, Riva C and Amiot MJ. (2017). Hydroxytyrosol in the prevention of the metabolic syndrome and related disorders. Nutrients. 9(3): 306
- Perna S, Spadaccini D, Botteri L, et al. (2019). Efficacy of bergamot: from anti-inflammatory and anti-oxidative mechanisms to clinical applications as preventative agent for cardiovascular morbidity, skin diseases, and mood alterations. Food Sci Nutr. 7(2): 369-84
- Mollace V, Sacco I, Janda E, et al. (2011). Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. Fitoterapia. 82(3): 309-16
- Toth PP, Patti AM, Nikolic D, et al. (2015). Bergamot reduces plasma lipids, atherogenic small dense LDL, and sublinical atherosclerosis in subjects with moderate hypercholesterolemia: a 6 months prospective study. Front Pharmacol. 6: 299
- Gliozzi M, Walker R, Muscoli S, et al. (2013). Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia. Int J Cardiol. 170(2): 140-5
- Sozen E, Demirel T, Ozer NK. (2019). Vitmain E: regulatory role in the cardiovascular system. IUBMB Life. 71(4): 507-15
- Saldeen T, Li D, Mehta JL. (1999). Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol. 34(4): 1208-15
- Samadian F, Dalili N, Jamalian A. (2016). Lifestyle modifications to prevent and control hypertension. Iran J Kidney Dis. 10(5): 237-63
- Bonnefont-Rousselot D. (2016). Resveratrol and cardiovascular diseases. Nutrients. 8(5): 250
- Singh RB, Niaz MA, Agarwal P, et al. (1996). A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction. Postgrad Med J. 72(843): 45-50
- Schaffer S and Kim HW. (2018). Effects and mechanisms of taurine as a therapeutic agent. Biomol Ther (Seoul). 26(3): 225-41
- Houston M. (2011). The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertens (Greenwich). 13(11): 843-7
- Ardisson LP, Rafacho BPM, Santos PP, et al. (2013). Taurine attenuates cardiac remodeling after myocardial infarction. Int J Cardiol. 168(5): 4925-6
- Aggarwal M, Bozkurt B, Panjrath G, et al. (2018) Lifestyle modifications for preventing and treating heart failure. J Am Coll Cardiol. 72(19): 2391-2405
- Qaradakhi T, Gadanec LK, Renee K, et al. (2020). The anti-inflammatory effect of taurine on cardiovascular disease. Nutrients. 12(9): E2847
- Sumi H, Hamada H, Nakanishi K, Hiratani H. (1990). Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 84(3): 139-43
- Weng Y, Yao J, Sparks S and Wang KY. (2017). Nattokinase: an oral antithrombotic agent for the prevention of cardiovascular disease. Int J Mol Sci. 18(3): 523
- Chen H, McGowan EM, Ren N, et al. (2018). Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases. Biomark Insights. 13: 1177271918785130
- Jafari M, Mousavi SM, Asgharzadeh A, Yazdani N. (2018). Coenzyme Q10 in the treatment of heart failure: a systematic review of systematic reviews. Indian Heart J. 70 (Suppl 1): S111-7
- Zozina VI, Covantev S, Goroshko OA, et al. (2018). Coenzyme q10 in cardiovascular and metabolic diseases: current state of the problem. Curr Cardiol Rev. 13(3): 164-74
- Digiesi V, Cantini F, Oradei A, et al. (1994). Coenzyme Q10 in essential hypertension. Mol Aspects Med. 15 Suppl: s257-63