hypercholesterolemia
This systematic review and meta-analyses explored the strength of evidence on efficacy and safety of Ayurvedic herbs for hypercholesterolemia. Methods: Literature searches were conducted and all randomized controlled trials on individuals with hypercholesterolemia using Ayurvedic herbs (alone or in combination) with an exposure period of ≥ 3 weeks were included. The primary outcomes were total cholesterol levels, adverse events, and other cardiovascular events.
A total of 32 studies with 1386 participants were found. They tested three Ayurvedic herbs:
- Allium sativum (garlic),
- Commiphora mukul (Guggulu),
- Nigella sativa (black cumin).
The average duration of intervention was 12 weeks. The meta-analysis of the trials showed that
- Guggulu reduced total cholesterol and low-density lipoprotein levels by 16.78 mg/dL (95% C.I. 13.96 to 2.61; p-value = 0.02) and 18.78 mg/dL (95% C.I. 34.07 to 3.48; p = 0.02), respectively.
- Garlic reduced LDL-C by 10.37 mg/dL (95% C.I. -17.58 to -3.16; p-value = 0.005).
- Black cumin lowered total cholesterol by 9.28 mg/dL (95% C.I. -17.36, to -1.19, p-value = 0.02).
Reported adverse side effects were minimal.
The authors concluded that there is moderate to high level of evidence from randomized controlled trials that the Ayurvedic herbs guggulu, garlic, and black cumin are moderately effective for reducing hypercholesterolemia. In addition, minimal evidence was found for any side effects associated with these herbs, positioning them as safe adjuvants to conventional treatments.
For the following reasons, I fail to see how these conclusions can be justified:
- Too many of the included studies are of poor quality.
- Only for garlic are there a sufficient number of trials for attempting to reach a generalizable conclusion.
- Giving garlic to patients with hypercholesterolemia is hardy Ayurvedic medicine.
- Even the effect of the best-tested herbal remedy, garlic, is not as large as the effects of conventional lipid-lowering drugs.
- Conclusions about the safety of medicines purely on the basis of RCTs are unreliable.
- The affiliations of the authors include the College of Integrative Medicine, Maharishi International University, Fairfield, USA, the School of Science of Consciousness, Maharishi University of Information Technology, Noida, India, and the Maharishi International University, Fairfield.
During Voltaire’s time, this famous quote was largely correct. But today, things are very different, and I often think this ‘bon mot’ ought to be re-phrased into ‘The art of alternative medicine consists in amusing the patient, while medics cure the disease’.
To illustrate this point, I shall schematically outline the story of a patient seeking care from a range of clinicians. The story is invented but nevertheless based on many real experiences of a similar nature.
Tom is in his mid 50s, happily married, mildly over-weight and under plenty of stress. In addition to holding a demanding job, he has recently moved home and, as a consequence of lots of heavy lifting, his whole body aches. He had previous episodes of back trouble and re-starts the exercises a physio once taught him. A few days later, the back-pain has improved and most other pains have subsided as well. Yet a dull and nagging pain around his left shoulder and arm persists.
He is tempted to see his GP, but his wife is fiercely alternative. She was also the one who dissuaded Tom from taking Statins for his high cholesterol and put him on Garlic pills instead. Now she gives Tom a bottle of her Rescue Remedy, but after a week of taking it Tom’s condition is unchanged. His wife therefore persuades him to consult alternative practitioners for his ‘shoulder problem’. Thus he sees a succession of her favourite clinicians.
THE CHIROPRACTOR examines Tom’s spine and diagnoses subluxations to be the root cause of his problem. Tom thus receives a series of spinal manipulations and feels a little improved each time. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.
THE ENERGY HEALER diagnoses a problem with Tom’s vital energy as the root cause of his persistent pain. Tom thus receives a series of healing sessions and feels a little improved each time. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.
THE REFLEXOLOGIST examines Tom’s foot and diagnoses knots on the sole of his foot to cause energy blockages which are the root cause of his problem. Tom thus receives a series of most agreeable foot massages and feels a little improved each time. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.
THE ACUPUNCTURIST examines Tom’s pulse and tongue and diagnoses a chi deficiency to be the root cause of his problem. Tom thus receives a series of acupuncture treatments and feels a little improved each time. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.
THE NATUROPATH examines Tom and diagnoses some form of auto-intoxication as the root cause of his problem. Tom thus receives a full program of detox and feels a little improved each time. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.
THE HOMEOPATH takes a long and detailed history and diagnoses a problem with Tom’s vital force to be the root cause of his pain. Tom thus receives a homeopathic remedy tailor-made for his needs and feels a little improved after taking it for a few days. But he is disappointed that the pain in the left shoulder and arm returns. His wife therefore tries to make another appointment for him.
But this time, Tom had enough. His pain has not really improved and he is increasingly feeling unwell.
At the risk of a marital dispute, he consults his GP. The doctor looks up Tom’s history, asks a few questions, conducts a brief physical examination, and arranges for Tom to see a specialist. A cardiologist diagnoses Tom to suffer from coronary heart disease due to a stenosis in one of his coronary arteries. She explains that Tom’s dull pain in the left shoulder and arm is a rather typical symptom of this condition.
Tom has to have a stent put into the affected coronary artery, receives several medications to lower his cholesterol and blood pressure, and is told to take up regular exercise, lose weight and make several other changes to his stressful life-style. Tom’s wife is told in no uncertain terms to stop dissuading her husband from taking his prescribed medicines, and the couple are both sent to see a dietician who offers advice and recommends a course on healthy cooking. Nobody leaves any doubt that not following this complex (holistic!) package of treatments and advice would be a serious risk to Tom’s life.
It has taken a while, but finally Tom is pain-free. More importantly, his prognosis has dramatically improved. The team who now look after him have no doubt that a major heart attack had been imminent, and Tom could easily have died had he continued to listen to the advice of multiple non-medically trained clinicians.
The root cause of his condition was misdiagnosed by all of them. In fact, the root cause was the atherosclerotic degeneration in his arteries. This may not be fully reversible, but even if the atherosclerotic process cannot be halted completely, it can be significantly slowed down such that he can live a full life.
My advice based on this invented and many real stories of a very similar nature is this:
- alternative practitioners are often good at pampering their patients;
- this may contribute to some perceived clinical improvements;
- in turn, this perceived benefit can motivate patients to continue their treatment despite residual symptoms;
- alternative practitioner’s claims about ‘root causes’ and holistic care are usually pure nonsense;
- their pampering may be agreeable, but it can undoubtedly cost lives.
Niacin – also known as vitamin B3 or nicotinic acid – is a natural compound (formula C
6H
5NO
2 ) and an essential nutrient for humans. It is water-soluble, which means it is not stored in the body. Excess amounts of the vitamin leave the body through the urine. That means we need a continuous supply of niacin in your diet.
Niacin is found in variety of foods, including liver, chicken, beef, fish, cereal, peanuts and legumes. It can also be synthesized from tryptophan, an essential amino acid found in protein. Niacin has long been an accepted treatment for high cholesterol. It is well-documented to increase the levels of high-density cholesterol (HDL or “good cholesterol”) and to decrease the levels of low-density cholesterol (LDL or “bad cholesterol”).
But what do these effects really mean? Do they translate into true health benefits? A brand-new study casts doubt on the value of niacin therapy:
After a pre-randomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants’ ability to take extended-release niacin without clinically significant adverse effects, the researchers randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (non-fatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization).
During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was 10 mg per deciliter (0.25 mmol/l) lower and an HDL cholesterol level that was 6 mg per deciliter (0.16 mmol/l) higher than the levels in those assigned to placebo. Thus the lipid-effects of previous studies were confirmed.
However, assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious and with an increased incidence of diabetes diagnoses as well as increases in serious adverse events associated with the gastrointestinal system, the musculoskeletal system, the skin and infections and bleeding.
Based of these data, the authors arrived at the following conclusion: among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events.
This extremely well-done trial is a poignant reminder of the fact that, in health care, we must never take our assumptions for granted. Here the underlying assumption was that the Niacin-induced lipid changes lead to a reduction of cardiovascular risks. Not only it proved to be erroneous but, through serious adverse effects, Niacin actually decreased patients’ health status.
The lessons from all this are straight forward, I think:
- ‘Natural’ does not necessarily mean safe.
- Long-established does not necessarily mean efficacious.
- Assumptions are merely assumptions, nothing more; if we want to make sure that they hold, we need to test them.
- When we finally do test assumptions, we better do it rigorously.
Yoga, it is often claimed, might be a unique method for disease prevention. One website, for instance, states that numerous studies show how yoga can help prevent these diseases: Heart disease, Alzheimer’s, Osteoporosis and Type II Diabetes.
Cardiovascular diseases (CVD) are responsible for more deaths than any other disease category. Preventing CVD is therefore of prime importance. But are the claims made for yoga really true? What does the reliable evidence tell us?
The aim of our systematic review was to determine the effects of yoga on the primary prevention of CVD. Extensive literature searches were performed to identify all RCTs lasting at least three months, involving healthy adults or people at high risk of CVD. Trials examined any type of yoga and the comparison groups received no intervention or minimal interventions. Outcomes of interest were clinical CVD events and major CVD risk factors. Trials that involved multifactorial lifestyle interventions or weight loss programmes were excluded.
We identified 11 RCTs with a total of just 800 participants. Style and duration of yoga differed between trials. About half of all the trial participants were at high risk of CVD. Most of the studies were at risk of performance bias, with inadequate details reported in many of them to judge the risk of selection bias. None of the studies reported cardiovascular mortality, all-cause mortality or non-fatal events, and most studies were small and short-term.
Yoga was found to produce an average reduction in diastolic blood pressure of 2.90 mmHg. The effect that was small but stable on sensitivity analysis. Triglycerides (-0.27 mmol/l) and high-density lipoprotein (HDL) cholesterol (0.08 mmol/l) were also positively affected. However, these findings were based on small, short-term studies at unclear or high risk of bias. There was no clear evidence of an effect on low-density lipoprotein (LDL) cholesterol. Adverse events, occurrence of type 2 diabetes and costs were not reported in any of the included studies. Quality of life was measured in three trials but the results were inconclusive.
Our conclusion: The limited evidence comes from small, short-term, low-quality studies. There is some evidence that yoga has favourable effects on diastolic blood pressure, HDL cholesterol and triglycerides, and uncertain effects on LDL cholesterol. These results should be considered as exploratory and interpreted with caution.
This systematic review thus offers both good and bad news. The good news is that yoga seems to hold some promise in the prevention of CVD. The bad news, however, is diverse:
- We cannot be sure what type of yoga is best; yoga can entail anything from regular exercise, to breathing techniques, to a complete and comprehensive change of life style.
- The effect sizes are far from remarkable.
- The quality of the research tends to be poor.
- Once again, we have to note that, by not reporting on adverse effects, alt med researchers are violating fundamental research ethics.
Many systematic reviews conclude by stating that more and better research is required – in the case of yoga, this platitude might actually be true.
Hypercholesterolemia is an important, independent risk factor for cardiovascular disease, according to a generally accepted wisdom. Measures to normalise elevated blood lipids include diet, exercise and drugs, of which statins are the most widely prescribed. But many people have become somewhat sceptical about the wide-spread use of statins: Traditionally, doctors have viewed statin drugs as the most effective way to lower high LDL cholesterol. But today researchers are starting to believe that statins may not be the magic bullet they’ve always been made out to be. Statins can cause severe adverse effects and some experts have questioned whether they generate more benefit than harm and suggested that ‘BIG PHARMA’ are pushing statins not for the benefit of public health but for maximising profit.
This begs the question: is there an alternative?
This RCT tested the efficacy of a dietary supplement providing 1.8 g/day esterified plant sterols and stanols to improve the fasting lipid profile of men and women with primary hypercholesterolemia. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Thirty subjects were randomized and all of them completed the trial.
Baseline (mean±standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6±4.2 mg/dL (6.11±0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8±3.0 mg/dL (1.47±0.08 mmol/L), LDL cholesterol 151.6±3.3 mg/dL (3.92±0.09 mmol/L), non-HDL cholesterol 179.7±4.6 mg/dL (4.64±0.12 mmol/L), and triglycerides 144.5±14.3 mg/dL (1.63±0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%), but not for triglycerides or HDL cholesterol.
The authors conclude that these results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia.
These findings are encouraging but certainly not rock solid. The study was too small, and the effect sizes were less than impressive. A brand-new systematic review, however, provides much more convincing data.
Its aim was to quantify the LDL-cholesterol-lowering effect of plant sterols/stanols as supplements. Eight eligible clinical trials were identified. Among the trials with a duration between 4 and 6 weeks, plant sterol/stanol dose ranged from 1.0 to 3.0 g/day administrated mainly with the main meals (2 or 3 times/day). Intake of plant sterol/stanol supplements decreased LDL-cholesterol concentrations by 12 mg/dL (0.31 mmol/L) compared with placebo. Further analysis showed no significant difference between the LDL-cholesterol-lowering action of plant sterols/stanols supplements vs foods enriched with plant sterols/stanols. The authors concluded that plant sterol/stanol supplements as part of a healthy diet represent an effective means of delivering LDL-cholesterol-lowering similar to plant sterols/stanols delivered in various food formats.
Crucially, this positive verdict does not stand alone. Another recent review included 5 trials and concluded that a dose-effect relationship of plant stanols in higher doses than currently recommended has been demonstrated by recent clinical studies and a meta-analysis.
Plant sterols seem to be not just effective but also safe: none of the trials published to date reported significant adverse effects. The only concern is the potential decrease in the concentrations of lipid-soluble antioxidants and vitamins, including β-carotene, α-tocopherol, lutein, and α-carotene. It is currently not clear whether these effects are clinically relevant.
The relative merits of phytosterols versus statins are not easy to evaluate. We have hundreds of studies of statins but just a few of sterols. This means our knowledge in this area is incomplete. Statins can cause serious adverse effects but their effects on blood lipids is about one order of magnitude larger that those of sterols. There is plenty of evidence to show that statins lower the risk of cardiovascular disease, while such data are missing for phytosterols.
The choice between statins and plant sterols is thus not easy, particularly considering the often emotional arguments and hype used in the ‘cholesterol-debate’. Phytosterols offer one more alternative therapy for lowering LDL-cholesterol levels. They seem safe and have the added attraction of being ‘natural’ – but the lipid-effects are relatively small, the impact on cardiovascular morbidity and mortality is uncertain, and fairly high doses are required to see any lipid-lowering at all.
