What does Curcumin and Co-Q10 do?

Curcumin and the curcuminoids are the primary bioactive compounds of turmeric (Curcuma longa) that give the root its yellow-orange colour. Other curcuminoids found in turmeric include dimethoxy-curcumin and bis-demethoxy-curcumin. Whole turmeric root also contains essentials oils, polysaccharides, proteins and many non-curcumin phytochemicals, which appear to be as active or important as curcumin itself. The whole spice, turmeric has been used in Indian Ayurvedic Medicine for centuries for healing and blood and skin purification.

Curcumin has been shown to interrupt the inflammatory cascade by inhibiting pro-inflammatory signalling agents, this finding triggered large scale interest in turmeric and curcumin in the research world. Inflammation is an immune response to injury or infection, inflammation brings heat and fluid to the site and can be accompanied by pain to halt further insult. Although inflammation is a necessary acute response; long term, chronic inflammation can become uncontrolled and lead to metabolic changes, chronic pain and the spread of inflammation that is subsequently linked to chronic conditions.

Despite potentially unfounded concerns about limited absorption of curcuminoids evidence suggests that turmeric and curcumin are absorbed and clinically effective without novel delivery systems such as polysorbate-80 (an artificial emulsifier which has been linked to gastric inflammation) or piperine (a black pepper extract that inhibits detoxification)4. Importantly, studies on enhanced bioavailability products may be exaggerated and difficult to interpret. The only study directly and rigorously comparing different formulations found that the levels of certain metabolites may vary greatly with different formulations and that the claimed bioavailability may be exaggerated. Furthermore, the absolute amount of curcuminoids in products need to be considered as some products contain very low levels compared to the original bioavailability study and below those levels used in clinical studies. Although a product may claim better bioavailability, it may not have been proven to be clinically effective.

Co-enzyme Q10 was first discovered in 1957 by Frederick Crane6. In the 1980’s Karl Folkers recognised the therapeutic potential of CoQ10 in cardiovascular disease and used it to treat patients with heart failure. In fact, CoQ10 is found in abundance in heart tissue. CoQ10 is an electron storing molecule that is utilised within the mitochondria; the powerhouses of the cells and site of aerobic energy production. Not only does CoQ10 store electrons for the quelling for free radicals and prevention of oxidative damage; it has a synergistic role in energy production at cellular level. It is the cellular level activity that implicates benefits for the heart and for cardiovascular protection.

Research has reported that consumption of CoQ10 as ubiquinone in humans results in a marked elevation of plasma CoQ10 as ubiquinol. CoQ10 is lipophilic, which means ‘fat loving’ and is transported in circulation by lipoproteins, subsequently it is essential that CoQ10 is consumed with a meal that contains fats.

‘No disease in the history of mankind exacts a greater toll in morbidity than heart or blood vessel disease.’

Clinical uses of Curcumin

• Antioxidant activity; oxidative damage is exerted from free radicals and reactive oxygen species, while eNOS and iNOS are a group of nitrogen isozymes that initiate the transformation of arginine to

citrulline and additionally produces nitric oxide free radicals. These are natural by-products of metabolism and products of the environment; for example; pollution. While certain medications or conditions can impact heart health through the generation of free radicals, increased heart rate and the reduction of heart tissue glutathione. 

• Autophagy is the process of digesting old or damaged cells while signaling for new cell formation, it is an ongoing phenomenon throughout living things. Yet, in the case of myocardial infarction a distinct disruption of autophagy occurs that damages myocardial cells and results in infarction. Subsequently, evidence shows that curcumin can stabilize the myocardial cells and exert a potentially protective and preventive action.

• Cardiac hypertrophy is the increased size of the heart in response to stresses, however sustained enlargement is a predictive risk factor for a cardiovascular event. A prime signaling messenger; p300 is a driver for cardiac hypertrophy and is a target for intervention, subsequently, mechanistic studies show that curcumin inhibits p30010.

• Cardiac fibrosis is the thickening of the heart tissues and valves and is driven by the pro-inflammatory signaling agent NFKappa-β, it is well known and demonstrated that curcumin is a potent inhibitor of NFKappa-β10, thus causing an interruption in the progression of cardiac fibrosis. In fact, curcumin has been shown to interrupt several pro-inflammatory agents and consequently exert a multi-factorial anti-inflammatory effect10.

• The sarcoplasmic reticulum is an organelle found in specific types of muscle fibres. Its function is to store calcium ions and then release them into the body, where they are absorbed when the muscles are in a relaxed position and released as the muscles contract. This process can be affected by incorrect timing of the Ca release subsequently affecting the cardiac heart muscle. Studies have shown that curcumin has improved the Ca homeostasis and improved the cardiac muscle function10.

• Studies have demonstrated the significant beneficial effects of curcumin on serum cholesterol and lipid peroxide levels. Since abnormal lipid metabolism contributes to the pathogenesis of atherosclerosis, therefore this suggests a potentially protective role of curcumin in atherosclerotic diseases10.

Clinical Findings for Curcumin

• curcumin and CHOLESTEROL REGULATION

• Dyslipidemia is a factor in acute coronary syndrome (ACS), subsequently a randomised double-blind controlled trial (RCT) was conducted to evaluate the effects of curcumin administration at 3 doses thrice daily (low dose 3 times 15 mg/day, moderate dose 3 times 30 mg/day, and high dose 3 times 60 mg/day) on total cholesterol level, LDL cholesterol level, HDL cholesterol level and triglyceride levels in ACS patients. Interestingly, the lowest dose of curcumin generated the greatest reduction in total cholesterol and greatest increase in HDL cholesterol. Furthermore, the largest dose of curcumin showed the greatest reduction of triglycerides. Similarly, another study showed that 10 mg of curcumin given twice a day for 28 days significantly lowered the serum LDL levels and increased the serum HDL levels in patients with atherosclerosis.

• curcumin as an ANTI-INFLAMMATORY

• Among the inflammatory signaling agents, interleukin-1 (IL-1), tumor necrosis factor α and IL-6 are the main inducers of inflammation, whereas others maintain inflammation, furthermore NF kappa-β plays a regulatory role in inflammation. IL-6 is multi-functional and is observed as a target for interrupting auto-immune responses. A meta-analysis investigated the efficacy of curcuminoids supplementation on circulating levels of IL-613. Nine RCTs were pooled, and it was concluded that curcuminoid (200mg – 6000mg daily for 2 weeks – 8 months) supplementation significantly reduced circulating IL-613.

Lipopolysaccharides are potent toxins produced by pathogenic bacteria, subsequently LPS trigger the activation of inflammatory signaling agents (TNF-α, IL-6) and the synthesis of reactive oxygen species; instigators of oxidative damage. It has been demonstrated that LPS toxicity leads to cardiac hypertrophy. However, a mechanistic investigation reported that 100mcg curcumin per kg of bodyweight reduced LPS toxicity in cardiac tissues and inhibited the contributing pathophysiology.

Curcumins ANTIOXIDANT effect

Curcuminoids have potentially important functional qualities including antioxidant properties. Humans are exposed to many toxins that are associated with oxidative damage and endothelial injury, vascular tissue damage and hypertension, while diesel exhaust particles are known to lead to cardiopulmonary problems and nicotine’s association with cardiovascular and lung diseases.

Mechanistic studies have shown a protective effect from curcumin against streptozotocin toxicity, through anti-inflammatory and antioxidant mechanisms. Furthermore, it was observed that curcumin therapy increased superoxide dismutase, catalase and glutathione production (endogenous antioxidant enzymes) in heart tissues.

Curcumin has been reported to reduce cardiotoxicity associated to diesel exhaust particles through anti-inflammatory pathways involving the reduction of markers of inflammation and inflammatory signaling agents.

Free radicals and reactive oxygen species are also by-products of metabolism. Subsequently a study investigated the effects of 90mg curcumin daily supplementation on exercise-induced oxidative stress in 10 male subjects. The curcumin was administered 2 hours prior to exercise or both 2 hours prior and immediately after exercise to assess its effects. It was reported that post exercise oxidant metabolites were significantly elevated in the placebo group but not in the single and double curcumin groups. Furthermore, the biological antioxidant potential of the blood was significantly increased compared to pre-exercise levels in the single and double curcumin groups suggesting that curcumin increases the blood’s anti-oxidant capacity

Curcumin and BLOOD VESSEL HEALTH

Arterial endothelial function in simple terms is the normal functioning of the blood vessels. Vascular inflammation and oxidative damage are highly associated with arterial endothelial dysfunction and subsequent increased risk of CVD. Given curcumin’s proven efficacy as an anti-inflammatory and antioxidant, a group of researchers investigated the effect of an 8-week treatment of 150mg daily of curcumin on endothelial function in 32 healthy, postmenopausal, sedentary females. Endothelial function was measured using flow mediated dilation measurement, this marker increased significantly in the curcumin group when compared to the control group. The results indicate that curcumin ingestion can improve flow mediated dilation in this population and potentially indicates an improvement in age related decline in endothelial function. A further random controlled double blind parallel prospective study, 59 subjects were assigned to placebo, 50mg curcumin or 200mg curcumin, for 8 weeks. Both the 50mg and 200mg curcumin groups saw increased flow mediated dilation compared to placebo. The 200mg curcumin group’s outcome was significant and clinically meaningful and therefore presents a simple lifestyle strategy for decreasing the risk of CVD.

• CARDIO-PROTECTIVE

CoQ10’s cardio-protective action was demonstrated in-vitro on human atrial structural tissues discarded during cardiac surgery. The tissues were immersed in CoQ10 or placebo for 30 minutes followed by 30 minutes of stimulated ischaemia. Young (<70 years) tissue showed post-ischaemic recovery whilst the aged (>70 years) showed a large increase in post- ischaemic recovery. Consequently, CoQ10 is considered to produce an age-specific protective effect.

Protection against myocardial ischemia has been demonstrated in 2 double blind crossover trials of CoQ10 in ischaemic heart disease patients that reported a reduction in angina, improved exercise tolerance and a reduction in ischaemic changes on an ECG. It was suggested that the results were attributable to the increased efficiency in myocardial mitochondrial energy production.

A small trial (n=23) of class II and III heart failure patients reported that 4 weeks of CoQ10 administration 100mg thrice daily improved exercise capacity VO2 max, cardiac ejection force and endothelium-dependant brachial artery dilation.

Class III and IV cardiomyopathy patients are expected to steadily worsen and die within 2 years under conventional therapy. Subsequently a double-blind and double-crossover trial was conducted to administer CoQ10 or placebo to patients diagnosed as having class III or IV cardiomyopathy. The CoQ10 group received CoQ10 followed by placebo and the placebo group vice versa. The CoQ10 group had significant increases in CoQ10 blood levels and cardiac function, but these results decreased during crossover to placebo. The placebo group had no change in CoQ10 blood levels and cardiac function during placebo treatment but increased in both parameters once they crossed over to CoQ10. Not only do these results indicate an extraordinary clinical improvement but suggest that consistent CoQ10 therapy might extend the lives of such patients.

Dilative cardiomyopathy is associated to low plasmatic and low myocardial CoQ10. Subsequently a trial investigated the effect of CoQ10 administration of dilative cardiomyopathy patients. 100mg CoQ10 daily was administered for 60 days followed by a washout period and crossover to placebo treatment. The trial focused on the left ventricular function and reported improved ejection fraction during the CoQ10 treatment, however the improvements were not maintained by placebo treatment.

The Q-SYMBIO trial involved the assessment of supplemental CoQ10 100mg thrice daily on biomarkers of heart failure on 420 patients who were followed up for 2 years. It was reported that CoQ10 administration significantly reduced a major adverse cardiovascular event; 15% in the CoQ10 group compared to 26% in the placebo, furthermore it was noted for its excellent tolerance and affordability making the compound attractive for CVD prevention and treatment. 

• DYSLIPIDEMIA 

• Dyslipidemia is an important risk factor for CVD and so, it has received an increase in attention to developing detection and treatment strategies. Consequently, a study was designed to investigate the effect of 120mg daily CoQ10 administration for 24 weeks on glycaemic or lipid profile and other MetS symptoms in subjects with dyslipidemia. At week 12 a reduction in systolic and diastolic blood pressure and in increase in total antioxidant capacity of the blood was observed in the CoQ10 group compared to placebo. While, at the end of the study period (week 24) a further decrease in blood pressure, further increase in total antioxidant capacity was observed besides reduced triglycerides, reduced LDL cholesterol and increased ApoA-I; a protein that clears fats and promotes HDL cholesterol, compared to placebo.

• STATIN-ASSOCIATED MYALGIA: CoQ10

• deficiency has been proposed to be causal in statin- induced myopathies. Patients prescribed statins who developed ≥2 myalgias on extremities within 60 days of starting the medication or change of medication were given 60mg CoQ10 twice daily for 1 month experienced a reduction in pain score from 10 to 6.5.

ANTI-INFLAMMATORY

With CVD being a leading cause of death worldwide a team of researchers investigated the effect of CoQ10 against markers of inflammation using systematic review and meta-analysis to pool existing data from 7 studies. The results showed a reducing trend in C- reactive protein (CRP) and a significant reduction in IL-6 concentrations following the supplementation with CoQ10 (60-300mg daily) for 8-12 weeks.

Recommended use: For use in adults, 1 to 2 capsules daily with food or as advised by their healthcare professional.

Safety: Human studies have used up to 8000 mg of curcumin per day for 3 months and found no toxicity.

Contraindications of Curcumin

: As turmeric has a mild anticoagulant effect the use of anticoagulant or antiplatelet medications are not advised. Experimental studies have shown that turmeric may reduce cyclophosphamide efficacy. Furthermore, turmeric may increase tamoxifen absorption and bioavailability.