Dr Des Corrigan adds a little spice to the research on the potential benefits of some dual-use plants

“Lose weight!” was the blunt response by an American physician when asked about the best preventive approach to Covid-19, because of the linkage between obesity and severe complications from the virus. Estimates suggest that 20-to-40 per cent of the world’s population are affected by metabolic syndrome, a cluster of conditions including high blood pressure, dyslipidaemia, abdominal obesity and hyperglycaemia that leads to an increased risk of cardiovascular disease (CVD), type 2 diabetes and insulin resistance. The WHO estimates that 1.6 billion people are overweight and of these, 400 million are obese. As a result, it has been predicted that annual mortality due to CVD is likely to reach 25 million by 2030.

Treatment involves mainly dietary and exercise changes, but pharmacological interventions are also used, even though adverse effects can be severe and many promising drugs have had to be withdrawn. Much attention has focused on so-called ‘nutraceuticals’ or functional foods as alternatives to synthetic molecules. These are plants with dual food and medicinal use, so not surprisingly, spices such as cardamom, cumin, celery, ginger, fenugreek and of course turmeric feature prominently. All have been the subject of research interest. A whole series of systematic reviews and meta-analysis of RCTs of these and other herbs and spices have appeared recently in journals such as Phytotherapy Research and the Journal of Ethnopharmacology.

Cardamom is one of my favourite spices and I just love the smell of the freshly-ground seeds, which is due to the mixture of cineole, terpinyl acetate, pinene and linalool found in its essential oil. Known as the ‘Queen of Spices’, it is used mainly as a flavouring, but it has also been used in traditional medicine in asthma, oral infections as well as digestive and kidney disorders. Pharmacological studies show that it has antioxidant, anti-inflammatory, cytotoxic and cardioprotective properties that have yet to be subjected to human studies. The one exception is in metabolic syndrome, where a 2019 systematic review and meta–analysis of five high-quality RCTs involved 361 participants, half of whom received 3g per day of a cardamom supplement for eight-to-12 weeks. In studies longer than eight weeks, there was a significant reduction in plasma triglyceride concentrations but no effect on any of the standard cholesterol levels.

A number of small-scale clinical trials of celery seed extract and one of its main constituents, n-butylphthalide, have shown hypotensive effects, possibly related to a diuretic effect, while two trials reported anti-obesity effects linked to changes in adiponectin levels. Cumin is another ‘seed’ widely used in curry powders and pastes. The essential oil from it was administered to 56 patients with metabolic syndrome in a randomised, triple-blind, placebo-controlled trial reported in 2019. Patients were given 75mg of oil or placebo in soft gel capsules three times a day for eight weeks. While diastolic BP was significantly lower in the cumin group, no other changes relevant to metabolic syndrome such as BMI, cholesterol or triglyceride levels were observed.

Cinnamon bark has attracted much attention because of its hypoglycaemic activity, apart from its widespread use as a spice. It has also been the subject of a 2019 systematic review of its effects on obesity. The meta-analysis involved 21 RCTs with 1,480 participants and found that cinnamon supplementation significantly reduces BMI, body weight and the waist-to-hip ratio, but that it had no effect on waist circumference or on body fat mass.
Saffron, another expensive spice, consists of the stamens laboriously collected from crocus flowers. It is rich in carotenoids, chiefly crocin. A meta-analysis of 14 RCTs involving 619 patients reported significant reductions in cholesterol and triglyceride levels, but no significant effect on body weight or on LDL-cholesterol levels. A sub-analysis showed that long-term saffron interventions could increase HDL-cholesterol.

Fenugreek seeds are widely used as a spice and flavouring and are used in Chinese and Indian medicine to treat hyperglycaemia, among other conditions. The Community Herbal Monograph (CHM) published by the EMA mentions hypoglycaemia as a possible side-effect that might need monitoring in diabetic patients. Strangely, the main indication accepted by the EMA for fenugreek is as a traditional herbal medicinal product for temporary loss of appetite.

Its accompanying Assessment Report, dating back to 2010, describes in significant detail extensive in vitro and in vivo studies of the hypoglycaemic effect, noting that clinical studies on the appetite stimulant, hypoglycaemic and hypolipidaemic effects could be described as exploratory, at best. That CHM is dated and there have been at least two meta-analyses, the first in 2014, involving 10 RCTs investigating the effect of the spice on fasting blood glucose (FBG) and HbA1c levels. Significant reductions in FBG and HbA1c levels were found, but trial quality was judged as being low and more research was needed.

The most recent systematic review was published earlier this year in the Journal of Ethnopharmacology and involved 560 participants enrolled in 12 RCTs. The meta-analysis found significant decreases in total cholesterol, LDL-cholesterol and triglycerides, with an increase in HDL-cholesterol but no change in body weight or BMI. The problem with these trials and those involving the other spices also is that unrealistically large doses were used. For example, eight of the fenugreek studies involved daily doses up to 100g and 6g of a total saponin extract in another.

What of our old friend turmeric and its mix of curcuminoids, chiefly curcumin? It keeps turning up like the proverbial bad penny — first as an adjuvant in cancer chemotherapy, then as a memory-enhancer in dementias, as well as featuring as an effective antiarthritic agent. While I am all in favour of natural remedies with proven effects, I must confess that I am amazed at the range of conditions that can apparently be treated with turmeric. To add to the list, there is a meta-analysis of eight RCTs in which 265 patients were given curcumin in relatively modest doses of 70-3,000mg per day for eight-to-12 weeks. Compared to a similar number given placebo, the turmeric group had significant reductions in BMI and in waist circumference, but no change in body weight.

The evidence base suggests that these spices, alone or in combination, are not ‘magic bullets’ for the prevention or treatment of metabolic syndrome. Rather, they demonstrate once again that plant secondary metabolites in foods, herbs and spices can nudge the body towards health, apart from adding to the enjoyment of eating meals prepared with them.

Dr Des Corrigan
Dr Des Corrigan

Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is a former Director of the School of Pharmacy at TCD and won the Lifetime Achievement Award at the 2009 Pharmacist Awards. He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011. He currently chairs the Advisory Subcommittee on Herbal Medicines and is a member of the Advisory Committee on Human Medicines at the IMB. He is a National Expert on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and he is an editorial board member of the Journal of Herbal Medicine and of FACT — Focus on Alternative and Complementary Therapy.