Important clinical studies with micronutrients

The call by Dr. Rath and Dr. Pauling for an international effort to eliminate heart disease was followed by tens of thousands of scientific and clinical publications over the past three decades. Following is a selection of important placebo-controlled, clinical studies supporting the role of micronutrients in the prevention and control of essentially all forms of cardiovascular disease.

Epidemiological studies on the correlation between the intake of micronutrients or food supplements and the risk of cardiovascular disease:

A study involving 11,348 adult Americans aged 25-74 years showed that both overall mortality and mortality from cardiovascular disease were associated with daily vitamin C intake. The subjects with the highest vitamin C intake had a 40% reduced risk of CVD mortality.
Enstrom JE et al. Vitamin C intake and mortality among a sample of the United States population.

A study at the University Hospital of Amsterdam with more than 2,700 participants showed a similar result. An increased vitamin C intake was associated with lower blood pressure and other positive parameters. Most importantly, the group of people with the highest vitamin C intake had a one-third lower risk of developing coronary heart disease compared with the group with the lowest intake.
Boekholdt SM et al. Plasma concentrations of ascorbic acid and C-reactive protein, and risk of future coronary artery disease, in apparently healthy men and women: the EPIC-Norfolk prospective population study.

Achievements in the treatment of coronary heart disease with food supplements/micronutrients

A study conducted at the University of California in Los Angeles showed that an increased vitamin intake had a positive effect on the progression of coronary heart disease. This study provided strong evidence because it was documented using coronary angiography. The researchers found an association between supplementary vitamin E intake and an angiographically demonstrated reduction in the progression of lesions in coronary arteries.
Hodis HN et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis.

In a double-blind, placebo-controlled clinical trial involving patients with coronary heart disease, a Norwegian team of doctors showed that micronutrient supplementation with folic acid (vitamin B9) and vitamin B12 had a positive effect on the blood supply to the coronary arteries. During the study period of two years, both basic and maximum blood flow in the coronary arteries were significantly improved by this micronutrient supplementation.
Bleie O. et al. Coronary blood flow in patients with stable coronary artery disease treated long term with folic acid and vitamin B12 [Anlage Bleie O – Coronary blood]

In a clinical study coordinated by the Department of Age Research and Preventive Oncology at the German Cancer Research Center in Heidelberg, several thousand study participants were observed over a period of 9.5 years. The study investigated the association between vitamin D deficiency and the most common causes of death. A direct link was found between vitamin D deficiency and the mortality rate from cardiovascular disease, cancer and other diseases.
Schöttker B et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study.

A clinical study conducted at the University of Kansas investigated the associations between vitamin D blood levels, vitamin D supplementation and the incidence of cardiovascular disease. Of 10,899 patients observed over a period of 5 years and 8 months, low vitamin D levels were associated with a significantly increased risk of cardiovascular disease and a shortened lifespan. In contrast, vitamin D supplementation was associated with a significantly increased life expectancy.
Vacek JL et al. Vitamin D deficiency and supplementation and relation to cardiovascular health.

A clinical study among more than 40,000 Japanese people, investigated the association between the intake of green tea, which is rich in natural polyphenols, and the occurrence of cardiovascular disease and cancer. The consumption of large quantities of green tea was associated with a significant reduction in cardiovascular mortality, including a clear reduction in deaths from stroke.
Kuriyama S et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.

In a clinical study in Stockholm, the association between the use of multivitamin supplements and the occurrence of heart attacks was investigated in almost 3,000 study participants. Participants taking multivitamins had a significantly reduced risk of heart attacks.
Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women–Stockholm Heart Epidemiology Program (SHEEP).

A clinical epidemiological study involving more than 2,400 participants in Finland investigated the association between blood levels of vitamin C and the occurrence of stroke. The study participants were patients with hypertension – a condition associated with an increased risk of stroke – who were observed over a period of 10.4 years. The results of the trials showed that – regardless of all other factors – male hypertensive patients with low vitamin C levels had a 2.6-fold higher risk of stroke.
Kurl S et al. Plasma vitamin C modifies the association between hypertension and risk of stroke.

An analysis of 8 clinical trials investigating the association between vitamin C supplementation and essential hypertension showed that vitamin C supplementation led to a significant reduction in blood pressure. For daily supplementation above 500 mg of vitamin C, these results were even statistically significant (P = 0.005). What is particularly remarkable about this research is the fact that these trials were conducted with patients suffering from so-called “essential hypertension”. This is a form of hypertension whose cause is unknown and therefore difficult to treat.
Guan Y et al. Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis.

In a double-blind, placebo-controlled trial with patients suffering from an early form of hypertension (pre-hypertension and stage 1 hypertension), the effect of quercetin on blood pressure was investigated. This dietary supplement led to a reduction in both systolic and diastolic blood pressure. The reduction in diastolic blood pressure was statistically significant (P < 0.01).
Randi L Edwards R L et al. Quercetin reduces blood pressure in hypertensive subjects.

In an evaluation of 11 double-blind, placebo-controlled trials, the correlation between dietary supplementation with the natural amino acid arginine and changes in blood pressure was investigated. The analysis of these trials showed that arginine supplementation led to a highly significant reduction in both systolic and diastolic blood pressure. One particularly remarkable aspect of this study was that it was published in the American Heart Journal, an official body of the American Heart Association (AHA), thus gaining wide recognition, especially among cardiologists.
Dong J-Y et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials.

An analysis of 12 clinical trials investigated the correlation between coenzyme Q10 supplementation, a cofactor of cellular energy metabolism, and hypertension. Based on all results, the researchers concluded that coenzyme Q10 supplementation can reduce systolic blood pressure by up to 17 points (mmHg) and diastolic blood pressure by up to 10 points. Among the clinical trials evaluated, 3 randomized controlled trials involving a total of 120 participants showed a highly significant reduction in blood pressure.
Rosenfeldt F L et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials.

In a randomized clinical trial involving patients suffering from chronic heart failure, the effect of dietary supplements containing a vitamin-mineral combination was investigated. The study was carried out at the Charité Clinic in Berlin and showed that the pumping function of the heart (left ventricular ejection fraction) was significantly improved by the dietary supplement. The patients’ quality of life also improved significantly.
Witte K et al. The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.

A study carried out by the University of Jerusalem examined the association between vitamin D blood levels and vitamin D supplementation on the mortality rate of patients with heart failure. The study compared 3,009 patients with low vitamin D levels with a control group comprising 46,825 participants . The study showed that vitamin D deficiency was significantly associated with increased mortality in heart failure patients. In addition, vitamin D supplementation was linked to a significant (P < 0.0001) reduction in mortality in heart failure patients.
Gotsman I et al. Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome.

In a comprehensive study conducted as part of the Third National Health and Nutrition Examination Survey, 13,131 participants were examined over a period of 12 years. The aim of the study was to find out if low vitamin D blood levels had an effect on the mortality rate of the study participants. The study results showed that insufficient vitamin D blood levels are associated with a significantly higher risk of dying from heart failure in particular, and cardiovascular disease in general. This study was published in the American Journal of Cardiology in 2012 and was widely distributed among cardiologists.
Liu L et al. Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from all-cause in United States adults.

Another randomized double-blind study was conducted as part of an international collaboration between the universities of Copenhagen, Melbourne, Vienna, Warsaw and other hospitals. The study included 420 patients and investigated the influence of coenzyme Q10 supplementation on the progression of chronic heart failure over a period of 2 years. According to the researchers, coenzyme Q10 is an “essential cofactor for energy production”. The results of the study showed that patients taking coenzyme Q10 supplements showed a significant reduction in mortality from cardiovascular disease and other conditions. The investigators and scientists who conducted this international study concluded: “Long-term coenzyme Q10 treatment of patients with chronic heart failure is safe, improves symptoms, and reduces major adverse cardiovascular events.”
Mortensen S A et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial.

60 patients with type 2 diabetes and low vitamin D levels were enrolled in a placebo-controlled, randomized clinical trial to investigate the effect of vitamin D supplementation on the progression of the disease. Patients who received a vitamin D supplement had a significant reduction in their long-term diabetes score (HbA1c). Blood pressure and blood lipid values (total and LDL cholesterol) were also positively influenced by vitamin D supplementation.
Upreti V et al. Effect of oral vitamin D supplementation on glycemic control in patients with type 2 diabetes mellitus with coexisting hypovitaminosis D: A parallel group placebo controlled randomized controlled pilot study.

In another randomized and controlled clinical trial, a joint team of researchers from the University Hospitals of Frankfurt and Hanover examined the effects of vitamin D administration on diabetes progression. The results of this clinical study showed that vitamin D supplementation significantly reduced insulin demands and significantly improved long-term blood glucose levels (HbA1c). No side effects were observed.
Bogdanou D et al. T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover.

A randomized clinical trial investigated the effect of vitamin C supplementation on blood glucose control and blood pressure in diabetic patients. After 4 months of vitamin C supplementation, participants showed an improvement in blood sugar levels and a reduction in blood pressure compared to the placebo group.
Mason S A et al. Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: Findings of a randomized cross-over trial.

A randomized, controlled clinical trial at Cairo University Medical Clinic examined the effect of a dietary supplement containing a combination of B vitamins (B1, B6 and B12) on patients with type 1 diabetes. After only 3 months, this dietary supplement led to a significant decrease in fasting blood glucose levels, long-term blood glucose (HbA1c), cholesterol, triglyceride and homocysteine levels. Particularly noteworthy about this study was the fact that it was conducted in children and adolescents who had been suffering from diabetes for more than 5 years and who showed early signs of diabetes-related kidney disease.
Elbarbary N S et al. Vitamin B complex supplementation as a homocysteine-lowering therapy for early stage diabetic nephropathy in pediatric patients with type 1 diabetes: A randomized controlled trial.

Diabetes is also a known risk factor during pregnancy, when the disease can lead to serious complications as a result of metabolic disorder. A randomized, controlled study at Shanghai University Hospital investigated the effect of vitamin D on the progression of gestational diabetes. Supplementation with high-dose vitamin D significantly improved the insulin needs and other parameters of diabetes in the study participants compared with the placebo group.
Zhang Q et al. Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial.

As early as 1992, the USDA Human Nutrition Research Center at Tufts University in Boston published a randomized field study involving several hundreds of participants of all age groups. The results of the study showed that increased vitamin C blood levels were associated with a reduction in LDL cholesterol (“bad cholesterol”) and an increase in HDL cholesterol (“good cholesterol”). As the human body cannot produce its own vitamin C, the blood level of this vitamin is only determined by food intake or dietary supplementation.
Jaques P F et al. Effects of vitamin C on high-density lipoprotein cholesterol and blood pressure.

A randomized, double-blind, placebo-controlled trial investigated the effect of two B vitamins (folic acid and vitamin B6) on the metabolism of patients with coronary heart disease. After three months of vitamin B supplementation, the three most important risk factors of fat metabolism showed a significant improvement. Blood levels of triglycerides and total cholesterol were reduced and HDL cholesterol (“good cholesterol”) was increased (P < 0.05). The blood levels of the risk factor homocysteine and inflammation values (interleukin-1 and IL-10) were also positively influenced by this dietary supplement.
Liu M et al. Effect of B vitamins supplementation on cardio-metabolic factors in patients with stable coronary artery disease: A randomized double-blind trial.

In another large randomized, placebo-controlled clinical trial, which involved several American universities, the influence of green tea extracts (catechins) was investigated. The study participants were all postmenopausal women, with 936 of them completing the one-year trial. Compared to the control group, catechin supplementation was associated with a significant reduction in total and LDL cholesterol levels (P = 0.0004 and P < 0.0001 respectively).
Samavat H et al. Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial.

A double-blind, placebo-controlled study conducted by the University of Nashville investigated the relationship between a dietary supplement containing green tea extract and its effect on cholesterol levels. 240 men and women over 18 years of age with low to moderate increases in blood cholesterol (hypercholesterolemia) were examined over a period of 3 months. Study participants who supplemented their diet with green tea extract were found to have a significant reduction in total and LDL cholesterol.
Maron D J et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial.