Review of Holford on Hayfever (Manchester Evening News article, again)

One interesting factor with much of Patrick Holford‘s work it the sheer amount of time that it takes to check its claims properly. Dealing with Holford’s statements in one, short, Manchester Evening News article has lead to me reading more than I’d ever wanted about fish cooking and Shinga doing some detailed reading and writing about MSM. This article just gives and gives, though – Coracle, from the awayfromthebench blog – has carried out a review of Holford’s claims in the Manchester Evening News. And, very kindly, e-mailed it to me to post here. So here it is – enjoy:

Not that long ago Patrick Holford was extensively quoted in an article about allergic rhinitis in the Manchester Evening News. In the article Mr Holford makes claims for a number of supplements he believes to be effective in the management of allergic rhinitis. It has already been pointed out that some of his advice is dubious, it therefore follows that the other claims by him should be subjected to critical analysis. Here I will attempt an amateur systematic review of the evidence for the recommended supplements.

Methods

The terms used in the original article were used to search the pubmed database (www.ncbi.nlm.nih.gov/pubmed) in conjunction with the phrase “allergic rhinitis”. Where freely available, full text articles were retrieved. When full text articles were not available abstracts alone were used. Previous reviews of the area were not included although observational studies were.

Results

Vitamin C Three clinical trials involving ascorbic acid for allergic rhinitis were identified. Each trial measured different outcomes and were of small size. Bucca et al (1990) found that 2g of vitamin C a day improved forced expiratory volume. A small trial using a range of doses found no benefit for vitamin C up to doses of 4 g a day when testing histamine response and skin wheal (Fortner et al, 1982). The largest trial found an improvement in allergic symptoms when treated with vitamin C (Podoshin et al, 1991). However, the details of this study are particularly sparse, it is not clear whether the trial was placebo controlled, what dose or doses of vitamin C were administered, nor for how long. A single observational study failed to find an association between plasma vitamin C levels and allergic rhinitis (Kampauer et al, 2006).

Reference n Dose (g) Measured outcome Favoured Intervention
Bucca 16 2 FEV Vitamin C
Fortner 6 1, 2 or 4 Skin wheel/ histamine Neither
Podoshin 60 NR Symptoms Vitamin C

Table 1: Summary of evidence for Vitamin C in allergic rhinitis. FEV, forced expiratory volume. NR, not reported.

Omega-3

Searching for omega 3 and allergic rhinitis returned the greatest number of hits for any of the interventions. Four observational studies and two clinical trials were identified. The results of the trials were equivocal, the larger trial found no benefit for fish oils in comparison to an olive oil placebo (Thien et al, 1993) when looking at occupational and recreational antigen challenge. The smaller of the two trials found benefit for EPA when compared to no dose in direct antigen challenge. The two studies used very similar doses of EPA and the larger trial was conducted for longer and in a real-world environment rather than a clinical setting. The four observational trials identified produce no clear pattern of benefit for omega-3 oils. The smallest trial found benefit for omega-3 with odds-ratio of 0.5 for the highest qurtile intake compared to the lowest quartile intake (Hoff et al, 2005). Kompauer et al (2005) failed to find any relationship between allergic rhinitis and omega-3 intake in a study of 740 adults. In a survey of 4104 children an increased risk of wheezing was associated with higher intake of fats in the form of margarine and butter (Farchi et al, 2003). The largest of the observational studies found that high ratios of n6:n3 omega fatty acids increased the risk of hay fever in males, and a higher total fat intake was associated with increased risk of hay fever in females (Trak-Fellermeier et al, 2004).

Reference n dose (g) Measured Outcome Favoured Intervention Type
Thien 37 3.5 EPA/day, 6 months Histamine levels None Placebo controlled trial
Rangi 7 3.5 EPA/day, 8 weeks Nasal blood flow, eosinophils, symptoms omega-3 Placebo controlled trial
Hoff 568 N/A allergic sensitisation omega-3 observational
Kompauer 740 N/A Hayfever, allergic sensitisation, total IgE No benefit for omega-3 observational
Farchi 4104 N/A Wheezing and allergic rhinitis Increased risk with increased fat intake observational
Trak-Fellermeier 802 N/A Hayfever, allergic sensitisation Higher risk associated with higher n6:n3 ratio observational

Table 2: Summary of evidence for omega 3 oils in allergic rhinitis. EPA, Eicosapentanoic acid. N/A, not applicable.

Quercitin

Searching for Quercitin returned two clinical trials. One, involving a combination antihistamine had no abstract and so was excluded from analysis (Miller, 1963). The other was a trial of Artemisia abrotanum L. extract in 12 patients (Remberg et al, 2004). No control group is reported. Reductions in nasal and conjunctival symptoms were reported. The concentration of flavenols, of which Quercitin is one, was reported at 2.5 microg/ml. No estimation of total Quercitin content or delivered dose is reported in the abstract.

Methylsulphonylmethane

A single clinical trial of Methylsulphonylmethane was retrieved from Pubmed. 55 subjects were recruited for an open-label trial for 30 days. Significant decreases in allergic symptoms were found in comparison to baseline (Barrageret al, 2002). Glutamine No reports were returned when searching for Glutamine and allergic rhinitis. Bromelain Only one experimental paper involving Bromelain for allergic rhinitis was found. One Rather than use as an anti-allergic agent, in this research Bromelain was used as an aggravating agent in mice. Inhibited and active forms of Bromelain were investigated and active forms were more potent in inducing sneezing and nasal rubbing (Suzuki et al, 2006).

Discussion

Allergic rhinitis is an unpleasant condition that affects approximately 16% of the UK population (Savage and Roy, 2005) and is increasingly common (Gupta et al, 2007). Dietary interventions have been recommended for the management of allergic rhinitis symptoms in areas of the lay press. The provision of evidence-based advice is important for the relief of symptomatic suffering. Here I have systematically reviewed the evidence for dietary intervention. Six dietary interventions were examined in the management of allergic rhinitis. The evidence base is generally poor, clinical trials are generally of small sizes and not always placebo controlled or blinded. The most evidence exists for vitamin C and omega 3 fatty acids. However, these trials are not uniform in the outcomes measured or their results. Only two clinical trials were reported for omega-3 oil intervention and the larger of the two reported no benefit for omega-3. The results of the observational studies were similarly conflicting with the largest study reporting increased risk of hay fever with increased fat intake. Of the other interventions the evidence was limited and of poor quality. Some reported benefit was found for Quercitin and MSM and the recommendation of Bromelain intervention appears to be counter-intuitive. No evidence was found for the non-essential amino-acid and the therapeutic rationale for taking supplements of crystalline glutamine, that could otherwise be provided by a balanced diet, is unclear. This study has been limited by the lack of full text articles. All analysis on the results has been based on content provided by the text of the report abstracts. Further information provided by full text articles may have provided a clearer picture of the results. The possibility of abstract bias, in which positive outcomes may be emphasised in the the abstract, cannot be discounted. However, abstract-bias cannot likewise estimated without full text availability. In conclusion there is insufficient evidence to recommend any of the dietary supplements suggested by Patrick Holford.

References

Barrager, Eleanor, Joseph R Veltmann, Alexander G Schauss, and Rebecca N Schiller. 2002. A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis. Journal of alternative and complementary medicine (New York, N.Y.) 8, no. 2 (April): 167-73.

Bucca, C, G Rolla, A Oliva, and J C Farina. 1990. Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis. Annals of allergy 65, no. 4 (October): 311-4.

Farchi, S, F Forastiere, N Agabiti, G Corbo, R Pistelli, C Fortes, et al. 2003. Dietary factors associated with wheezing and allergic rhinitis in children. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 22, no. 5 (November): 772-80.

Fortner, B R, R E Danziger, P S Rabinowitz, and H S Nelson. 1982. The effect of ascorbic acid on cutaneous and nasal response to histamine and allergen. The Journal of allergy and clinical immunology 69, no. 6 (June): 484-8. Gupta, R, A Sheikh, D P Strachan, and H R Anderson. 2007. Time trends in allergic disorders in the UK. Thorax 62, no. 1 (January): 91-6.

Hoff, S, H Seiler, J Heinrich, I Kompauer, A Nieters, N Becker, et al. 2005.Allergic sensitisation and allergic rhinitis are associated with n-3 polyunsaturated fatty acids in the diet and in red blood cell membranes. European journal of clinical nutrition 59, no. 9 (September): 1071-80.

Kompauer, Iris, Hans Demmelmair, Berthold Koletzko, Gabriele Bolte, Jakob Linseisen, and Joachim Heinrich. 2005. Association of fatty acids in serum phospholipids with hay fever, specific and total immunoglobulin E. The British journal of nutrition 93, no. 4 (April): 529-35.

MILLER, J. 1963. CLINICAL TRIAL OF A MULTIPHASIC ANTIHISTAMINIC PREPARATION (CLEMIZOLE, QUERCETIN, AMPHETAMINE). Annals of allergy 21:692-7. Podoshin, L, R Gertner, and M Fradis. 1991. Treatment of perennial allergic rhinitis with ascorbic acid solution. Ear, nose, & throat journal 70, no. 1 (January): 54-5.

Rangi, S P, M H Serwonska, G A Lenahan, W C Pickett, V A Blake, S Sample, et al. 1990. Suppression by ingested eicosapentaenoic acid of the increases in nasal mucosal blood flow and eosinophilia of ryegrass-allergic reactions. The Journal of allergy and clinical immunology 85, no. 2 (February): 484-9.

Remberg, P, L Björk, T Hedner, and O Sterner. 2004. Characteristics, clinical effect profile and tolerability of a nasal spray preparation of Artemisia abrotanum L. for allergic rhinitis. Phytomedicine : international journal of phytotherapy and phytopharmacology 11, no. 1 (January): 36-42.

Savage, Julian, and Dev Roy. 2005. Allergic rhinitis: an update. Journal of the Royal Society of Health 125, no. 4 (July): 172-5.

Suzuki, Motohiko, Makoto Itoh, Nobuo Ohta, Yoshihisa Nakamura, Akihiko Moriyama, Tamami Matsumoto, et al. 2006. Blocking of protease allergens with inhibitors reduces allergic responses in allergic rhinitis and other allergic diseases. Acta oto-laryngologica 126, no. 7 (July): 746-51.

Thien, F C, J M Mencia-Huerta, and T H Lee. 1993. Dietary fish oil effects on seasonal hay fever and asthma in pollen-sensitive subjects. The American review of respiratory disease 147, no. 5 (May): 1138-43.

Trak-Fellermeier, M A, S Brasche, G Winkler, B Koletzko, and J Heinrich. 2004. Food and fatty acid intake and atopic disease in adults. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 23, no. 4 (April): 575-82.

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5 Comments

Filed under allergies, hayfever, IgE, manchester evening news, msm, omega 3, patrick holford, vitamin c

5 responses to “Review of Holford on Hayfever (Manchester Evening News article, again)

  1. Shinga

    1 Comment – Show Original Post

    Shinga said…
    Thorough work, Coracle.

    I am concerned that parents might try and treat their children’s hayfever with dietary modifications without consulting their GP. GPs need to know when a child has allergic rhinitis because it is frequently a prelude to the development of asthma. If a child has allergic rhinitis, eczema and asthma then they have a worrying trifecta of conditions that needs careful observation and management.

    Finally, I can not overemphasise a fact that should be self-evident. Children are not small adults: it is not always possible to calculate a safe or effective dosage for them by scaling down from an adult dose. Further, it is not unusual for particular drugs or substances to have what is known as a paradoxical effect in children: e.g., Ritalin is a stimulant drug that is said to calm children and and help them to focus on tasks.

    I’ve looked at papers for several of the cited supplements but aside from the Omega 3 studies, I haven’t seen any studies to establish safe dosages in children or that can confirm that the supplements are safe for children.

    Regards – Shinga

  2. Claire

    “GPs need to know when a child has allergic rhinitis because it is frequently a prelude to the development of asthma. If a child has allergic rhinitis, eczema and asthma then they have a worrying trifecta of conditions that needs careful observation and management…”

    I agree Shinga, though I’m afraid to say that my personal experience is that the ‘worrying trifecta’ was not picked up at all in GP, even though paediatric allergy specialists are particularly concerned about such children suffering from complex allergic disease. Even in higher-risk cases where diagnosed food allergy exists alongside asthma, I’m sorry to say that I know personally several people who were unaware that sub-optimal asthma control in such a context increases the risk of a fatal allergic reaction.

    Part of the problem of not having enough clinically trained specialists – a point which you have made in your breath spa blog

  3. Shinga

    It is worrying, Claire. I really ought to look through some parenting or women’s magazines to see if any of them highlight the trifecta in their never-ending lists of “10 Things to Ask Your Doctor” or “10 Things that Could Save Your Health/Relationship” etc.

    I wonder if there is better awareness of the paramount importance of adequate control, particularly so when there is a co-morbidity of allergy, when people are under the supervision of a special asthma clinic or Asthma Nurse?

    I would really far rather that people were getting appropriate advice from GPs or other healthcare providers than trying to self-manage by following Holford’s advice. But I fully accept that this motherhood and apple pie advice is undercut by the lack of access to specialist allergy care.

    It’s a shame that some of the ‘superfluous’ junior doctors caught up in the MTAS nonsense can not be offered training positions in the management of allergy and allergic disease.

    Regards – Shinga

  4. Claire

    Yes, it is worrying. The National Allergy Strategy Group’s submission to the current House of Lords inquiry summarises concerns about the present state of NHS allergy care (http://www.parliament.uk/documents/upload/st1nasg.pdf), including this issue of co-morbidity and also the difficulty of getting funding to study the role of allergy in sudden, unexpected asthma deaths (my pet concern).

    I was fairly gobsmacked recently when a former neighbour – educated, middle class, articulate – was telling me about her son, mid 20s, had eczema and asthma as a child, also peanut allergy. He has, she said, outgrown the asthma and eczema, still avoids peanuts though has let the epipen prescription lapse and no longer has a current prescription for a rescue inhaler. He hasn’t been near a doctor for years. In the last few weeks he has been having hayfever symptoms and as she also suffers and can get wheezy this time of year, she asked if I though she should just ask her GP for an extra rescue inhaler which she could give to her son! I know of a GP with an excellent reputation for these conditions in the surgery she and her son attend, so I urged her to get her son to see this doctor asap.
    So yes, I agree it would be an excellent idea if the lifestyle magazines could educate people about the need to take these conditions seriously, rather than breathlessly (ahem!) hyping unproven supplements.

  5. Shinga

    If you can’t be breathless on World Asthma Day – when can you?

    I know that the young man in question is an adult but I don’t understand why the surgery doesn’t have a follow-up system for anaphylacts to say, “Hi, we were concerned to see that your epipen prescription has lapsed. Come in and see us to help us update our records and talk to you about current recommendations”.

    I’m grumbling quite a lot at present. A neighbour tipped me off that the daytime medical soap on BBC has just developed a storyline with one of the GPs deciding to become a GP Homeopath. Very kindly, the neighbour has recorded it for me so I may transcribe any useful parts later.

    It mightn’t be dramatic – but seriously, even on World Asthma Day, the BBC couldn’t manage a sensible item about asthma on a medical soap?

    Regards – Shinga

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