Spirulina in allergy, rhinitis and immunomodulation

Spirulina or arthrospira is a blue-green alga that has gained its claim to fame after it was successfully used by the US National Aeronautical Space Agency as a dietary supplement for astronauts on space missions. Spirulina is a microscopic and filamentous cyanobacterium that derives its name from the spiral or helical nature of its filaments. It has a long history of use as a food, with reports of its use during the Aztec civilisation.Reference Dillon, Phuc and Dubacq¹ Spirulina refers to the dried biomass of Arthrospira platensis, an oxygenic, photosynthetic bacterium found worldwide in fresh and salt water. This alga represents an important dietary staple for humans and has been used as a source of protein and vitamin supplementation, without any significant side effects. Apart from a high (up to 70 per cent) protein content, it also contains vitamins, especially B₁₂ and provitamin A (β-carotenes), and minerals, especially iron. It is also rich in phenolic acids, tocopherols and γ-linolenic acid.Reference Dillon, Phuc and Dubacq¹ Spirulina lacks cellulose cell walls and therefore can be easily digested.Reference Dillon, Phuc and Dubacq¹ There are many toxicological studies that have proven its safety. Spirulina belongs to the substances classed as ‘generally recognized as safe’ by the US Food and Drug Administration.Reference Tarantino²

Spirulina is relatively easy to cultivate but flourishes only in alkaline lakes with an extremely high pH and in large outdoor ponds under controlled conditions. There are only a few areas worldwide that have the ideal sunny climate for production of this alga, including Greece (Nigrita, Serres), Japan, India, the United States and Spain. Currently, spirulina can be found in health food stores and is sold mainly as a dietary supplement in the form of health drinks or tablets. Microalgae have been used for more than 10 years as dietary supplements, without significant side effects.Reference Kay³

It has been well documented that spirulina exhibits anti-inflammatory properties by inhibiting the release of histamine from mast cells.Reference Yang, Lee and Kim⁴

In a recent randomised, double-blinded, placebo-controlled trial,Reference Mao, Van de Water and Gershwin⁵ individuals with allergic rhinitis were fed daily for 12 weeks with either spirulina or placebo. Peripheral blood mononuclear cells were isolated before and after this period and the level of cytokines (interleukin-4, interferon-γ and interleukin-2), important in regulating immunoglobulin (Ig) E mediated allergy, were measured. A high dose of spirulina was shown to significantly reduce interleukin-4 levels, by 32 per cent, demonstrating the protective effects of this microalga against allergic rhinitis.

Ishii et al. studied the influence of spirulina on Ig A levels in human salivaReference Ishii, Katoch, Okuwaki and Hayashi⁶ and demonstrated enhanced IgA production, suggesting a pivotal role of the microalga in mucosal immunity.

A Japanese team identified the molecular mechanism of spirulina's effects on the human immune system by analysing the blood cells of volunteers before and after oral administration of a hot water extract of Spirulina platensis. Interferon-γ production and natural killer cell damage were increased after administration of the microalga extracts to male volunteers.Reference Hirahashi, Matsumoto, Hazeki, Saeki, Ui and Seya⁷

It is well understood that nutrient deficiency can alter immunity, prompting changes in T-cell production, secretory IgA antibody response, cytokines and natural killer cell activity. The above studies suggest that spirulina may modulate the immune system via its role in addressing nutritional deficiencies. More randomised, controlled trials are required before spirulina can be used for allergic rhinitis patients. A multicentre, placebo-controlled trial is under way in Greece, where spirulina is widely produced.

Ginkgo biloba in tinnitus

Ginkgo biloba, or maiden hair tree, has been well known for its medicinal value for thousands of years. Chinese manuscripts dating from the Han dynasty (circa 206BC to 220AD) mention the use of ginkgo leaf extracts for skin problems, lung ailments and to improve blood circulation. Traditionally, the leaves have either been eaten raw or drunk as a tea. Whilst scientific evidence remains lacking, this has not prevented the growing popularity of complementary and alternative medicine; sales of herbal medicines have boomed into a 4 billion dollar industry in the United States. Ginkgo biloba, now marketed as an extract, is one of the top 10 best-selling herbs in health food stores.

The two main active ingredients in ginkgo, flavanoids and terpenoids, are responsible for a vast array of pharmacologic functions, including neuroprotection, antioxidation, free-radical scavenging and membrane stabilisation.Reference Sierpina, Wollschlaeger and Blumenthal⁸ In addition, ginkgo improves microcirculation by increasing the fluidity of blood through inhibition of platelet-activating factor. These characteristics have resulted in G biloba being commonly used to improve cognitive function, memory, peripheral vascular disease and even tinnitus. Whilst studiesReference Sierpina, Wollschlaeger and Blumenthal⁸ have supported the use of G biloba in early-stage Alzheimer's disease, vascular dementia and intermittent claudication, its role in tinnitus remains equivocal.

Various studies over the last two decades have attempted to show the benefits of G biloba in tinnitus. Unfortunately, early trials were hampered by small sample size, unrandomised sampling or suboptimal dosing. Ernst and Stevinson suggested that extracts of G biloba were effective in treating tinnitus but concluded that further trials, both methodologically rigorous and consistent in outcome measures, were first needed.Reference Ernst and Stevinson⁹ Of the five studies analysed by these authors, only one was included in the Cochrane review.Reference Hilton and Stuart¹⁰ The other trials were deemed too methodologically weak to be accepted as evidence of a beneficial effect. It was concluded that the limited evidence available did not demonstrate the effectiveness of G biloba for tinnitus, especially in cases in which tinnitus was the primary complaint. Furthermore, G biloba had no significant benefit over placebo.Reference Drew and Davies^11, Reference Rejali, Sivakumar and Balaji¹² There was also no reliable evidence to assess the use of G biloba in cases in which tinnitus was associated with cerebral insufficiency.

Although the majority of trials have been proved wanting, many do report an improvement in tinnitus. This positive benefit cannot be explained by a placebo effect alone. This has led to a theory that some patients who derive benefit from G biloba may have a degree of cerebral insufficiency. Were this to be true and G biloba proved to be an effective treatment, the question arises of its mechanism of action. The pharmacological profile of G biloba is complex and its action in tinnitus unknown. Moreover, the aetiology of tinnitus remains unanswered and is presumably multi-faceted. Objective methods for assessing the severity of tinnitus are also unavailable. It is thus unsurprising that no ‘gold standard’ treatment for tinnitus exists.

Tinnitus in cognitive insufficiency is fundamentally different from primary tinnitus. For example, the former condition may be caused by central vascular insufficiency or a neural metabolic disorder, whereas the initiating pathology of the latter condition is a cochlear disorder. Changes in vascular perfusion and neuronal metabolism are well documented effects of G biloba.Reference Drew and Davies^11, Reference Rejali, Sivakumar and Balaji¹² Improved cognitive functioning due to G biloba allows habituation to the tinnitus. If G biloba causes a significant improvement in overall cognitive functioning, then a positive effect on tinnitus may be real but non-specific. Thus, G biloba may be effective in this subgroup of patients. More work is needed to verify this before the case is closed on the use of Ginkgo biloba in tinnitus.

Nutritional supplements in sinusitis

Vitamins and nutritional supplements are extremely popular, especially in a modern society which actively pursues healthy living and a wholesome lifestyle. What is commonly overlooked is the fact that a balanced diet would in itself meet all nutritional requirements. Whilst vitamins are important to prevent or treat deficiency, the fad for mega-vitamin therapy is unscientific and can be harmful. This section focuses on three supplements used in the context of sinusitis: cod liver oil, multivitamins and pineapple enzyme.

Cod liver oil is derived from the livers of white fish such as cod and halibut. It is an important source of both vitamin D and long chain fatty acids. These constituents have an anti-inflammatory role. Linday et al. studied four children diagnosed with chronic or recurrent sinusitis who were given a course of cod liver oil and a multivitamin.Reference Linday, Dolitsky and Shindledecker¹³ Three had a ‘positive response’, reported as improved sinus symptoms, reduced frequency of acute sinusitis and fewer visits to the doctor. Based on the results of this small study, these authors concluded that this adjunctive therapy was an inexpensive, non-invasive intervention for children with chronic or recurrent sinusitis. An earlier trial by the same group, this time studying the effects of multivitamins and cod liver oil on otitis media, showed that responders required a shorter duration of antibiotics than before supplementation.Reference Linday, Shindledecker, Dolitsky and Pippenger¹⁴

Bromelain is a complex mixture of proteinases derived from pineapple stem. Anecdotal use of bromelain includes the treatment of sinusitis, arthritis, dental pain, and post-operative pain and inflammation, presumably through an anti-inflammatory mechanism, inhibition of platelet aggregation or fibrinolytic activity. Only one relevant study was found, involving 116 children recruited from 19 centres located throughout Germany.Reference Braun, Schneider and Beuth¹⁵ These children were randomised into three treatment groups: bromelain monotherapy, bromelain with standard therapy and standard therapy alone. The primary measure of effectiveness in the different treatment groups was the duration of symptoms. Patients in the bromelain monotherapy group showed a statistically significantly faster recovery from symptoms compared with the other treatment groups.

Although the benefits of dietary supplementation in cases of nutritional deficiency are undeniable, there is a lack of evidence-based trials to support its use in the prevention or adjunctive treatment of otolaryngological infections.

Vertigoheel in vertigo

Vertigoheel^® (US, Albuquerque, NM. Heel Inc) is a composite remedy containing four active ingredients: ambra grisea, cocculus indicus, conium maculatum and petroleum. It has botanical, zoological and mineral origins. It is believed to have a positive effect on microcirculation.Reference Weiser, Strösser and Klein¹⁶ In an unrandomised, open study of 12 patients, both flow rates and haematocrit improved after 12 weeks of Vertigoheel therapy. Early results published by the manufacturers showed that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine.Reference Weiser, Strösser and Klein¹⁶ The authors concluded that Vertigoheel had a similar efficacy to betahistine. These collaborators then performed a meta-analysis of four studies evaluating Vertigoheel compared with betahistine, G biloba and dimenhydrinate.Reference Schneider, Klein and Weiser¹⁷ This review suggested that Vertigoheel resulted in an equivalent reduction of symptoms compared with each of the other control groups. A recent randomised, controlled trial also showed that Vertigoheel was a suitable alternative to G biloba in the treatment of atherosclerosis-related vertigo.Reference Issing, Klein and Weiser¹⁸ The frequency, duration and intensity of vertigo episodes after a six week course of Vertigoheel were comparable to those after G biloba therapy.