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Monday, 29 April 2013

Can Spirulina Produce a Sustained Virological Response in Chronic Hep C? More Studies Here Please.

I was going to give the whole algae as immune stimulants theme a rest, until Silvia Hinojosa-Price sent me this paper.
Spirulina Platensis versus Silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial.

I've been reading these Hep C natural therapy papers for many years now and this is the first to record SVR. Essentially, this means that the treatment (Spirulina, a simple dried extract at 500mg 3x daily) was associated with undetectable virus levels after 6 months treatment. Only in 13.3% of the subjects (4 of 30, with another 2, or 6.7% having a significant drop of over 2 log) but still - this NEVER happens in clinical trials of "natural" or "alternative" therapies. The best will often lower viral load, but not to undetectable levels. HCV researchers never use the word "cure", but having no virus is as close as it gets. There are a few caveats I'll add later, but this is an impressive paper. I don't often see papers of this sort so well written or with the data so well presented. There's not much left to the imagination, which is how it should be. The authors are coming from a conventional, standard of care background and have had their interest piqued by patients reporting beneficial effects from Spirulina supplements; so they ran this clinical trial. 

The motivation to conduct this study, "apart from the theoretically convincing background", was the unintended data coming from some of our patients who took Spirulina as nutritional supplement and reported to us marked improvement of the general well being and sexual activity. From this probing experience, as well as from the results of Danoff A, et al. [44] and Soykan A, et al. [45] who reported an association of chronic HCV with depressed sexual functions independent of depression, we opted to compare the effect of both treatments on sexual functions beside the other efficacy parameters in such patients. We assumed that improvement in sexual appetite; frequency and performance are logical indicators for the improvement in the overall wellbeing. Our results went in agreement with this assumption.
This is how it should be done, respecting the patients' anecdote as a hypothesis generator, yet these kinds of trials often end in disappointment. But not this time. Yakoot and Salem were smart enough to allow the trial to last 6 months. They made the logical assumption that the time needed for any response to Spirulina would be at least as long as that needed for a response to Interferon-based therapies.
We hypothesized that there must be a time needed to establish and solidify the immune mechanisms behind the activation, release and action of endogenous interferons and other interplaying cells and mediators. Even the parenterally administered high dose of interferon alpha took some months to manifest its maximal virological response, that is why we wait at least 3 months to predict the sustained virological response through the early complete or even partial virological response.

Silymarin was used as an "active placebo". In other words, Spirulina was compared to extract of Milk Thistle seeds (140mg 3x daily), the supplement most likely to be used by chronic Hep C sufferers, but one that has only a small objectively measurable effect (at least, in this basic dosage form: but you can see here that other, more bioavailable forms might be worth testing).
Lo and behold, one of the Silymarin group (1 of 29) had an SVR. This reduced the significance of the 4 Spirulina SVRs and doesn't seem to be commented on. For what it's worth, Silymarin does have inhibitory effects on HCV replication, but these should be mild at the levels attained in a 140mg 3x daily dosing, and it's the first I've ever heard of SVR from Silymarin. However, there is a natural rate of spontaneous clearance in chronic Hep C, estimated at 1% per year, though no-one really knows and most clinicians would rather not follow up such cases. Lazarus was a disappointment to his doctor.
The patients with the lowest viral loads were the most likely to have an SVR in response to Spirulina. In those patients with viral loads below 100,000 the difference between Spirulina and Silymarin was statistically significant.
Our results showed significantly greater effects of Spirulina than Silymarin on most studied parameters including the significantly greater reduction of serum ALT and the greater improvement in both disease specific health related quality of life and sexual functions scores. Though the virological response rates were not statistically significantly different between the 2 treatment groups, yet it reached the level of significance with the one sided Z test for proportions in those who presented with low or intermediate baseline viremia.

One limitation was the absence of post-treatment follow-up. 
It is the main limitation of our study that we did not follow up patients for one year treatment followed by 6 months off-treatment period as the case in the protocols for the study of interferon alpha based therapy. We designed this relatively short term pilot study to answer a simple research question; is there any therapeutically feasible potential for Spirulina in chronic HCV patients, worthy to conduct a larger study with longer follow up period.
I would expect that some of the SVR cases would relapse once they stopped taking Spirulina; after all, this happens with conventional drugs. But why should anyone stop taking Spirulina? It would be no imposition at all to keep taking it for the rest of one's life, indeed it probably be a good idea even if the sustained viral response didn't depend on it.
This study was mainly focusing to help a considerable percentage of chronic HCV patients who are facing the situation of contraindication, intolerability or non-response to the current gold standard therapy. They usually become feeling hopeless and unsecure with deterioration in their overall wellbeing, functional status and quality of life. If further studies confirm our results with reproducibility, this could be an alternative treatment in such situations if at least it can improve quality of life, physical activity and performance. We did not focus on the luxury of sustained virological response at this exploratory stage, but it will be our objective in the coming planned study.

Where to from here?

The raised issues from the already discussed in-vitro and preclinical data about the potential immune stimulation and virus entry blocking also urged us to plan to test a new hypothesis; could the complementary therapy with Spirulina improve the response to the current gold standard antiviral therapy?. This will be tried to answer in our next study; through testing the effect of combining Spirulina with the current gold standard therapy, or the effect of offering a lead-in course for those who have high baseline virus load.
I would like to see a longer study of constant treatment, similar to the long-running Japanese zinc carnosinate (Polaprezinc) study. And there is no reason why the dose couldn't be increased. The nutrients that support Interferon - B12, D3 and retinol - could be optimized. And so on.

About the Physician Authors; AA Salem has authored 420 medical papers (well not all of those, possibly a common name, but certainly including 5 based on clinical experience of HCV cases. M Yakoot has authored 13 papers, mostly clinical trials of dietary supplements or reviews of OTC drugs. He appeared on Egyptian TV during the swine flu outbreak there.)
Dr Yakoot presents the results of the Spirulina paper in the last 2 minutes of this video, which also features some cool animations of HCV, LDL and LDL-R interaction:

The competing interests: 
Beovita-Safe Pharma, a Joint German Egyptian Company, Katzbachstr. 29, D-10965 Berlin, had supplied the drugs and partly the costs of the laboratory tests.
There seems to be nothing unique or patentable about Beovita-Safe Pharma's Spirulina or Silymarin products that would prevent the results being replicated with another company's products. I suspect Beovita-Safe Pharma's motivation was to have the use of their products accepted as safe and justified by the clinicians treating their customers. I wonder what Beovita-Safe Pharma will do with this additional information. They'll certainly be motivated to support other trials.
We opted to use the whole herbal extract and not any one of the fractionated bioactive molecules presuming that the whole natural multi-components as previously discussed in introduction could offer not only antiviral activity but also other immune enhancing activities that might be summated together to produce therapeutic effects on this state of chronic viral infection that evades the immune system.

Update: I looked at Spirulina products while shopping today. Most are whole dried Spirulina 500mg tablets, but I found one product that was a "herbal extract" of 2,300mg Spirulina in an approximately 500mg cap (I suspect) together with 50mcg selenium from selenomethionine. It had been made in New Zealand for the Japanese market.
This may be close to the Beovita product. I hope to find out more - including, what is the iron content of the Beovita tabs? 1g of Spirulina can supply 3mg iron and a standard dose of whole dried spirulina is 9g daily.


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