Bee venom acupuncture is a form of acupuncture in which bee venom is applied to the tips of acupuncture needles, stingers are extracted from bees, or bees are held with an instrument exposing the stinger, and applied to acupoints on the skin.
Bee venom consisting of multiple anti-inflammatory compounds such as melittin, adolapin, apamin. Other substances such as phospholipase A2 can be anti-inflammatory in low concentrations and pro-inflammatory in others. However, bee venom also contains proinflammatory substances, melittin, mast cell degranulation peptide 401, and histamine.
Bee venom acupuncture has been used to treat a number of conditions such as lumbar disc disease, osteoarthritis of the knee, rheumatoid arthritis, adhesive capsulitis, lateral epicondylitis, peripheral neuropathies, stroke and Parkinson’s Disease. The quality of these studies tends to be so poor that any verdict on the effectiveness of bee venom acupuncture would be premature.
A new clinical trial of bee-venom acupuncture for rheumatoid arthritis (RA) might change this situation. A total of 120 cases of RA patients were randomized into bee-sting acupuncture group (treatment) and western medicine group (control). The patients of the control group were treated by oral administration of Methotrexate (10 mg, once a week) and Celecoxlb (0.2 g, once a day). Those of the treatment group received 5 to 15 bee stings of Ashi-points or acupoints according to different conditions and corporeity, and with the bee-sting retained for about 5 min every time, once every other day. The treatment lasted for 8 weeks. The therapeutic effect was assessed by examining:
- symptoms and signs of the affected joints as morning stiffness duration,
- swollen/tender joint counts (indexes),
- handgrip strength,
- 15 m-walking time,
- visual analogue scale (VAS),
- Disease Activity Score including a 28-joint count (DAS 28),
- rheumatoid factor (RF),
- erythrocyte sedimentation rate (ESR),
- C-reactive protein (CRP),
- anti-cyclic citrullinated peptide antibody (ACCPA).
For assessing the safety of bee-venom acupuncture, the patients’ responses of fever, enlargement of lymph nodes, regional red and swollen, itching, blood and urine tests for routine were examined.
Findings of DAS 28 responses displayed that of the two 60 cases in the control and bee-venom acupuncture groups, 15 and 18 experienced marked improvement, 33 and 32 were effective, 12 and 10 ineffective, with the effective rates being 80% and 83. 33%, respectively. No significant difference was found between the two groups in the effective rate (P>0.05). After the treatment, both groups have witnessed a marked decrease in the levels of morning stiffness duration, arthralgia index, swollen joint count index, joint tenderness index, 15 m walking time, VAS, RF, ESR, CRP and ACCPA, and an obvious increase of handgrip strength relevant to their own levels of pre-treatment in each group (P<0.05). There were no significant differences between the two groups in the abovementioned indexes (P>0.05). The routine blood test, routine urine test, routine stool test, electrocardiogram result, the function of liver and kidney and other security index were within the normal range, without any significant adverse effects found after bee-stinging treatment.
The authors (from the Department of Acupuncture and Moxibustion, Bao’an Hospital of Traditional Chinese Medicine, Shenzhen, China) concluded that bee-venom acupuncture therapy for RA patients is safe and effective, worthy of popularization and application in clinical practice.
Where to start? There is so much – perhaps I just comment on the conclusion:
- Safety cannot be assessed on the basis of such a small sample. Bee venom can cause anaphylaxis, and several deaths have been reported in patients who successfully received the therapy prior to the adverse event. Because there is no adverse-effect monitoring system, the incidence of adverse events is unknown. Stating that it is safe, is therefore a big mistake.
- The trial was a non-superiority study. As such, it needs a much larger sample to be able to make claims about effectiveness.
- From the above two points, it follows that popularization and application in clinical practice would be a stupid exercise.
So, what is left over from this seemingly rigorous RCT?
(except perhaps a re-affirmation of my often-voiced fear that we must take TCM-studies from China with more than just one pinch of salt)
We have repeatedly discussed the fact that alternative medicine (AM) is by no means free of risks. I find it helpful to divide them into two broad categories:
- direct risks of the intervention (such as stroke due to neck manipulation, or cardiac tamponade caused by acupuncture, or liver damage due to a herbal remedy) and
- indirect risks usually due to the advice given by AM practitioners.
The latter category is often more important than the former. It includes delay of effective treatment due to treatment with an ineffective or less effective form of AM. It is clear that this will cause patients to suffer unnecessarily.
Several investigations have recently highlighted this important problem, including this study from Singapore which assessed the predictors of AM-use in patients with early inflammatory arthritis (EIA), and its impact on delay to initiation of disease-modifying anti-rheumatic drugs (DMARD). Data were collected prospectively from EIA patients aged ≥ 21 years. Current or prior AM-use was ascertained by face-to-face interviews. Predictors of AM-use and its effect on time to DMARD initiation were determined by multivariate logistic regression and Cox proportional hazards, respectively.
One hundred and eighty patients were included: 83.9% had rheumatoid arthritis, 57% were seropositive. Median (IQR). Chinese race, being non-English speaking, smoking and high DAS28 were independent predictors of AM-use. AM-users initiated DMARD later (median [IQR] 21.5 [13.1-30.4] vs. 15.6 [9.4-22.7] weeks in non-users, P = 0.005). AM-use and higher DAS28 were associated with a longer delay to DMARD initiation. Race, education level, being non-English speaking, smoking and sero-positivity were not associated.
The authors concluded that healthcare professionals should be aware of the unique challenges in treating patients with EIA in Asia. Healthcare beliefs regarding AM may need to be addressed to reduce treatment delay.
These findings are not dissimilar to results previously discussed, for instance:
- AM-use delays cancer diagnosis.
- The advice of non-medically qualified practitioners may delay cancer therapy.
- Chiropractic care may delay referral to effective treatment.
- Consultations with homeopaths can delay effective therapy.
The only solution to the problem I can think of would be to educate AM practitioners and the public such that they are aware of the issue and do everything possible to prevent such problems. But this is, of course, easier said than done, and it seems more than just optimistic to hope that such endeavours might be successful. The public is currently bombarded with misleading information and outright lies about AM (many of my previous post have addressed this problem). And practitioners would have to operate against their own financial interest to prevent these problems from occurring.
This means that treatment delays caused by AM-use and advice from AM practitioners are inevitable…
unless you have a better idea.
If so, please let me know.
As I have said on several occasions before: I am constantly on the lookout for new rigorous science that supports the claims of alternative medicine. Thus I was delighted to find a recent and potentially important article with some positive evidence.
Fish oil has been studied extensively in terms of its effects on health. We know that it has powerful anti-inflammatory properties and might thus benefit a wide range of conditions. However, the effects of FO in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA.
A new study has tried to fill this gap by examining the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
Patients with RA <12 months’ duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.
In the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.
The authors concluded that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.
So here we have a dietary supplement that actually might generate more good than harm! There is a mountain of data of good research on the subject. We understand the mechanism of action and we have encouraging clinical evidence. Some people might still say that we do not need to take supplements in order to benefit from the health effects of FO, consuming fatty fish regularly might have the same effects. This is true, of course, but the amount of fish that one would need to eat every day would probably be too large for most people’s taste.
The drawback (from the perspective of alternative medicine) in all this is, of course, that some experts might deny that FO has much to do with alternative medicine. Again: what do we call alternative medicine that works? We call it MEDICINE! And perhaps FO is an excellent example of exactly that.
For this blog, I am constantly on the lookout for ‘positive news’ about alternative medicine. Admittedly, I rarely find any.
All the more delighted I was when I found this new study aimed to analyse the association between dietary long-chain n-3 polyunsaturated fatty acids (PUFAs) and incidence of rheumatoid arthritis (RA) in middle-aged and older women.
Data on diet were collected in 1987 and 1997 via a self-administered food-frequency questionnaire (FFQ). The risk of RA associated with dietary long-chain n-3 PUFAs and fish intake was estimated using Cox proportional hazard regression models, adjusted for age, cigarette smoking, alcohol intake, use of aspirin and energy intake.
The results show that, among 32 232 women born 1914–1948, 205 RA cases were identified during a mean follow-up of 7.5 years. An intake of dietary long-chain n-3 PUFAs (FFQ1997) of more than 0.21 g/day (lowest quintile) was associated with a 35% decreased risk of developing RA compared with a lower intake. Long-term intake consistently higher than 0.21 g/day (according to both FFQ1987 and FFQ1997) was associated with a 52% decreased risk. Consistent long-term consumption (FFQ1987 and FFQ1997) of fish ≥1 serving per week compared with<1 was associated with a 29% decrease in risk.
The authors concluded that this prospective study of women supports the hypothesis that dietary intake of long-chain n-3 PUFAs may play a role in aetiology of RA.
These are interesting findings which originate from a good investigation and which are interpreted with the necessary caution. As all epidemiological data, this study is open to a number of confounding factors, and it is therefore impossible to make firm causal inferences. The results thus do not led themselves to clinical recommendation, but they are an indication that more definitive research is warranted, all the more so since we have plausible mechanisms to explain the observed findings.
A most encouraging development for alternative medicine, one could conclude. But is this really true? Most experts would be surprised, I think, to find that PUFA-consumption should fall under the umbrella of alternative medicine. Remember: What do we call alternative medicine that works? It is called MEDICINE!
One alternative therapy that I have so far almost entirely neglected is Ayurveda. It is said to be one of the fastest growing system within this sector. Ayurvedic healing includes herbs, nutrition, panchakarma cleansing, acupressure massage, Yoga, Sanskrit, and Jyotish (Vedic astrology). The website of the ‘Choppra Center’ explains: Recognizing that human beings are part of nature, Ayurveda describes three fundamental energies that govern our inner and outer environments: movement, transformation, and structure. Known in Sanskrit as Vata (Wind), Pitta (Fire), and Kapha (Earth), these primary forces are responsible for the characteristics of our mind and body. Each of us has a unique proportion of these three forces that shapes our nature. If Vata is dominant in our system, we tend to be thin, light, enthusiastic, energetic, and changeable. If Pitta predominates in our nature, we tend to be intense, intelligent, and goal-oriented and we have a strong appetite for life. When Kapha prevails, we tend to be easy-going, methodical, and nurturing. Although each of us has all three forces, most people have one or two elements that predominate.
However, the evidence for its effectiveness is not overwhelming. In 2007, we published a systematic review of Ayurvedic treatments for rheumatoid arthritis (RA). Seven studies met our inclusion criteria. Trials tested either Ayurvedic medicine against placebo or other Ayurvedic medicines. Of 3 placebo-controlled RCTs, one high-quality trial did not show benefit of the active treatment against placebo, while another incompletely reported study indicated beneficial effects of an Ayurvedic medicine. A further incompletely reported study showed no significant difference. The remaining 4 trials were difficult to interpret because they tested an Ayurvedic medicine against other Ayurvedic medicines whose effects were not proven. We concluded that there is a paucity of RCTs of Ayurvedic medicines for RA. The existing RCTs fail to show convincingly that such treatments are effective therapeutic options for RA.
Because of this paucity of reliable evidence, any new assessments are welcome.
The aim of this article was to review and meta-analyze the effectiveness and safety of different Ayurvedic interventions in patients with osteoarthritis (OA). 138 electronic databases were searched through August 2013. Randomized controlled trials, randomized crossover studies, cluster-randomized trials, and non-randomized controlled clinical trials were eligible. Adults with pre-diagnosed OA were included as participants.
Interventions were included as Ayurvedic, if they were explicitly labeled as such. The main outcome measures were pain, physical function, and global improvement. Risk of bias was assessed using the Cochrane risk of bias tool.
19 randomized and 14 non-randomized controlled trials on 12 different drugs and 3 non-pharmaceutical interventions with a total of 2,952 patients were included. For the compound preparation, Rumalaya, large and apparently unbiased effects beyond placebo were found for pain (standardized mean difference [SMD] -3.73; 95 % confidence interval [CI] -4.97, -2.50; P < 0.01) and global improvement (risk ratio 12.20; 95 % CI 5.83, 25.54; P < 0.01).
There was also some evidence that effects of the herbal compound preparation Shunti-Guduchi are comparable to those of glucosamine for pain (SMD 0.08; 95 % CI -0.20, 0.36; P = 0.56) and function (SMD 0.15; 95 % CI -0.12, 0.36; P = 0.41).
Based on single trials, positive effects were found for the compound preparations RA-11, Reosto, and Siriraj Wattana. For Boswellia serrata, Lepidium Sativum, a Boswellia serrata containing multicomponent formulation and the compounds Nirgundi Taila, Panchatikta Ghrita Guggulu, and Rhumayog, and for non-pharmacological interventions like Ayurvedic massage, steam therapy, and enema, no evidence for significant effects against potential methodological bias was found.
No severe adverse events were observed in any of the trials.
The authors concluded that the drugs Rumalaya and Shunti-Guduchi seem to be safe and effective drugs for treatment of OA-patients, based on these data. However, several limitations relate to clinical research on Ayurveda. Well-planned, well-conducted and well-published trials are warranted to improve the evidence for Ayurvedic interventions.
I am, of course, pleased that other too have noticed the paucity of good evidence and recommend more and better research into this area. There are, however, several things that worry me about this systematic review:
- How can there be a total absence of adverse effects? Even placebos would generate some.
- The conclusion that Rumalaya and Shunti-Guduchi are safe does not seem justified on the basis of just a few trials.
- My own review found quite encouraging effects for Boswellia serrate.
- 138 electronic databases? I did not even know that so many existed!
- I am also concerned by the way the treatments found to be ‘safe and effective’ are being promoted on the internet:
Rumalaya is a phytopharmaceutical formulation that relieves joint and bone ache associated with various orthopedic ailments. Its natural ingredients possess potent anti-inflammatory properties that alleviate pain. As an immunomodulator, Rumalaya modulates both the humoral and cell-mediated immune response to aches and pain. The medicine has strong anti-arthritic properties that work to combat arthritis.
- Rheumatic arthritis
- Rheumatoid arthritis
- Cervical and lumbar spondylosis
- Frozen shoulder
- Traumatic inflammatory conditions like fibrositis, bursitis, synovitis, capsulitis, tenosynovitis, myositis and sciatica.
I fail to see good evidence to support most of these claims.
Lastly, I find that the authors fail to warn the public in sufficiently strong terms of some of the drawbacks of Ayurvedic medicines. Many of them seem not to be safe. One of several problems is that they have been shown to be often contaminated/adulterated with toxic substances such as heavy metals.
My conclusion about the value of Ayurvedic medicines is therefore not so optimistic: EFFICACY IS USUALLY MORE THAN DOUBTFUL, WHILE RISKS ARE WELL-DOCUMENTED.
The fish oil (FO) story began when a young Danish doctor noticed that there were no heart attacks in Greenland. Large epidemiological studies were initiated, mechanistic investigations followed, and a huge amount of fascinating data emerged. Today, we know more about FO than most other dietary supplements.
Fish oil contains large amounts of omega-3 fatty acids which are thought to be beneficial in treating hypertriglyceridemia, preventing heart disease. In addition, FO is often recommended for a wide variety of other conditions, such as cancer, depression, and macular degeneration. Perhaps the most compelling evidence exists in the realm of inflammatory diseases; the mechanism of action of FO is well-studied and includes powerful anti-inflammatory properties.
Australian rheumatologists just published a study of FO supplements for patients suffering from rheumatoid arthritis (RA). Specifically, they examined the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
Patients with chronic RA <12 months’ who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or plaacebo (low dose FO for masking). These groups were given 5.5 or 0.4 g/day, respectively, of eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.
The results indicate that, the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.
The authors conclude that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.
These findings are most encouraging, particularly as they collaborate those of systematic reviews which concluded that evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs and …there is evidence from 6 of 14 randomized controlled trials supporting a favourable effect of n-3 LCP supplementation in decreasing joint inflammation in RA. And you don’t need to buy the supplements either; regularly eating lots of fatty fish like mackerel, sardine or salmon has the same effects.
So, here we have an alternative, ‘natural’, dietary supplement or diet that is supported by reasonably sound evidence for efficacy, that has very few adverse effects (the main one being contamination of the supplement with toxins), that generates a host of potentially useful effects on other organ systems, that is affordable, that has a plausible mechanism of action…. Hold on, I hear some people interrupting me, FO is not an alternative medicine, it is mainstream! Exactly, an alternative medicine that works is called….MEDICINE.