Alternatives
The author is defining Alternatives as any approach to treating UC which is not a drug, nor food or drink but which has at least some reasonable evidence that it might help to induce or extend remission. This includes drug-like compounds which are not included in official medical guidelines, but which have good evidence of 1) safety and 2) at least some efficacy.
We can divide Alternatives into categories, on which we provide more information below.
a) Curcumin
b) Indigo naturalis (Qing Dai)
c) Aloe vera gel
d) Vitamin D
2) Commercial probiotic supplements
a) Visbiome/Vivomixx (formerly VSL#3)
b) Mutaflor (E. coli strain Nissle 1917)
a) Faecal microbiota transplant (FMT)
b) Helminth therapy
a) Yoga / meditation
b) Exercise
1) Drug-Like Compounds
Some people may refer to the list of compounds below as "supplements", but the author prefers the term "drug-like compounds" given that they are all pharmacologically active. Just because an ingredient is "natural", does not mean it is safe. Medical professionals will not generally prescribe these (except in the case of vitamin D). Therefore, if you intend to try these as add-ons to existing conventional treatments, you will need to ensure you procure high quality, safe formulations. Always tell your physician what supplements you intend to take alongside your conventional medication, as drug-drug interactions may occur in some cases.
Of the four compounds below, there is good evidence for very strong safety in three of them, with Qing Dai exhibiting some adverse safety signals in some studies. However, the author has chosen to include it given its high efficacy in some patients and its popularity in the UC community, but does not recommend taking it without consulting first with your physician.
There are other drug-like compounds which have some evidence for efficacy in UC, such as wheatgrass, ginger and fish oil, but the standard of evidence is generally lower in these cases so the author has chosen to exclude them for now.
Curcumin
This compound, derived from tumeric, has been used by people to treat inflammatory diseases for thousands of years. Multiple studies have found that it can help to safely induce remission (here) and extend remission (here) when used as an add-on therapy to conventional drugs. An Israel study (here) in 50 active UC patients taking mesalazine found that 53% of those on 3 grams of curcumin per day achieved clinical remission at 4 weeks, compared to 0% on placebo.
When procuring curcumin, it is essential to avoid accidentally buying "turmeric", which is only comprised of c. 3% curcumin, vs c. 95% in purified forms. Optimal dose sizes are also unknown, with studies testing doses over a large range (0.1 - 3.0 grams/day); a dose around 0.5 grams per day is likely sufficient in the author's view.
Indigo Naturalis
Indigo naturalis (Qing Dai) is a traditional Chinese herbal medicine which has been used for centuries. It is a pharmacologically active ingredient extracted from the stems and leaves of various plants. Several studies have shown that it is startingly effective at inducing remission in patients with active UC (response rates generally >70%, here). However, adverse events have also been a concern, particularly those affecting the liver, so the author cannot recommend taking this treatment without physician agreement and liver monitoring.
A Japanese study (here) in 86 UC patients found that rates of clinical remission at week 8 were 55% for 1 gram/day and 38% at 2 grams/day vs just 5% for placebo. These are impressive results, but unfortunately around 1 in 6 patients recorded mild liver impairment and the trial was stopped early as one patient reported a case of pulmonary arterial hypertension. Another study in 2018 (here) in 46 patients administered indigo naturalis at 1 gram/day for 2 weeks and reported no serious adverse events and strong efficacy, so this medicine may be more appropriately used for a short (<2 weeks) course to induce remission. That said, a final study (here) gave 2g/day of indigo naturalis to 33 moderate-severely active UC patients for a year and saw clinical remission rates of 58%, 70% and 73% at week 4, 8 and 52 respectively. Blood biomarker results also very significantly improved. These are scarcely believable results, especially given that the patients were heavily pre-treated (>1/3 steroid-dependent, 36% on anti-TNFs, 55% on a thiopurine), but there was also a high safety burden (4/33 patients suffered serious adverse events), though it is currently unclear whether these were treatment-related. In the author's view, indigo naturalis is best used cautiously and not for long periods.
Aloe Vera Gel
The inner part of the aloe vera plant leaf contains a gel-like substance which has been used as traditional medicine in many cultures for thousands of years. It is believed to have potent anti-inflammatory effects on the body, but the precise mechanism of action is unknown and may include many pathways (here). There is only a single human study that the author has been able to find (here), but it shows that in 44 patients with active UC, clinical remission was achieved in 30% of cases vs 7% for placebo. The treatment also appears to be safe, with no differences in side effects to placebo. Using this treatment as an add-on to standard therapy may therefore be considered, but care should be taken to procure pure aloe vera gel (not juice), with 100ml twice daily being the dose used in the only human study.
Vitamin D
It has been noted that UC patients with low vitamin D levels are more likely to have more severe disease (here), with greater need for more potent treatments and hospitalisations. They are also more likely to suffer from a relapse if in remission (here). One study (here) suggested that supplementing vitamin-D deficit UC patients with 2,000 IU / day of vitamin D led to reduced UC disease activity. Given this evidence, it is the author's view that vitamin D supplementation in the Winter is most like a good idea, especially if you live in the Northern hemisphere or are of non-white ethnicity. There are also health benefits outside of UC (here) and no safety concerns provided you do not take too much (no supplements should be necessary in Spring or Summer).
2) Commercial Probiotic Supplements
Probiotics are live microbes that are believed to play a part in digestion, metabolism and immune system function. They are sometimes referred to as "good bacteria" in the media, but this downplays the truly crucial role the microbiome (the community of microbes that live in our gut) plays. One hypothesis argues that an imbalance in the microbiome (dysbiosis) may be the ultimate cause of UC (see study published in Nature, here) and that probiotics may therefore be part of the solution. This is unlikely to be the whole story, but it is undoubtedly true that probiotics have been shown to play a positive role in the treatment of UC, though the author believes that combining probiotics with the right diet to support them is likely to be just as important.
Many excellent probiotics come in the form of food or drink (see the Food and Drink sections), but there are also countless commercial probiotic brands in the market, many of them making extraordinary claims. However, to the author's knowledge, only two brands have been tested in randomised, controlled clinical trials in a UC population: VSL#3 (now known as Visbiome/Vivomixx) and Mutaflor (E. coli strain Nissle 1917).
Please note that the author has no commercial links with any company that supplies these products.
Visbiome
This probiotic formulation, known as Visbiome in the US, Vivomixx in Europe and formerly known as VSL#3, consists of 8 different bacterial strains and was invented by Professor Claudio De Simone in the 1990s. Each dose (taken daily) delivers c. 450 billion live bacteria to your gut. Multiple small studies have shown that Visbiome reduces the severity of UC (here), increases the chances of achieving remission (here) and increases the chances of staying in remission (here). The largest study (147 UC patients) tested VSL#3 vs placebo and found at 12 weeks that 43% of those on VSL#3 were in remission vs 16% of those on placebo (here). There were no safety concerns, but stomach bloating is common for the first couple of days. It appears that the action of VSL#3 is synergistic with other drugs such as mesalazine (here) and is therefore likely to be a good add-on therapy as it comes with no additional side effect burden.
A legal note:
The original VSL#3 formulation is now branded as Visbiome (US) and Vivomixx (Europe), but there are other similar formulations being sold under the old VSL#3 brand, without the permission of the formulation patent owner (De Simone). Litigation has been brought in the US and Europe against various entities which are accused of passing off their formulations as the original formulation; the author is not a lawyer and has no opinion or advice to give on any of these proceedings.
Mutaflor
This probiotic strain (E. coli strain Nissle 1917) was isolated from the stool of a WWI soldier who was noted as remaining completely healthy at a time when most of his comrades contracted multiple gut-related diseases. It was purified and decades later went through rigorous testing. It is now classed as a medical product for regulatory purposes (here) and is thus held to higher standards on product quality and evidence of clinical efficacy. It is sold in capsules with an enteric coating that dissolves in the colon, ensuring that the contents are released at the appropriate stage. It is the only probiotic to have demonstrated in a randomised clinical trial (here) that it is equally effective as mesalazine in maintaining remission in UC patients. However, it can be a challenge to source this product, as the manufacturer only sells in it a select few countries, though third party sellers do offer it in other regions.
3) Medical Procedures
Faecal microbiota transplant (FMT)
This procedure, also known as a stool transplant, involves taking stool samples from gut-healthy volunteers and transferring them into the colon of a UC patient. This transfer may be carried out by use of an endoscope, enema, orogastric tube or in the form of capsules taken by mouth. FMT is believed to work by correcting dysbiosis (i.e. an imbalance in gut microbiota, which is hypothesised as being a potential cause of UC). This mechanism of action is clearly understandable in the treatment of C. difficile, as the influx of harmless or beneficial bacteria crowds out the pathogenic C. difficile which is causing the issue, but in the case of UC, it is much more complex. Although it is well established that UC patients have dysbiosis (here), the precise microbial imbalance differs from person to person and what is driving the disease may not always be the same. This fact may also explain why FMT appears to be so effective in some UC cases and yet has no effect at all on others - for example, it may be that the bacteria species the UC person was "missing" were not present in the donor sample. In any case, this topic remains subject to intense scientific debate, with many competing theories proposed.
Efficacy is Very Hit and Miss
FMT is now acknowledged as the most effective way of treating recurrent C. difficile infection (here), beating antibiotics by a considerable margin; however, in the case of UC, it not as clear. Around 1/3 of UC patients with active disease who undergo FMT enter clinical remission (here), but the strength and length of remission varies greatly. Some patients see a tremendous benefit and can apparently drop all UC medications and remain in deep remission, sometimes, apparently, permanently (here), but 2/3 see no benefit. FMT clearly holds huge potential as a future standard treatment, but there are also many unanswered questions and for this reason, many doctors take a fairly negative view towards it.
The Many Unknowns
While in clinical trials, most adverse events have been gastrointestinal complaints that soon resolved (here), other trials of FMT for other diseases have shown some serious safety concerns, such as transferred infections, aggravation of UC, the induction of other immune-mediated disorders and even obesity (here).
There are also many questions around how is best to administer FMT. These include whether it best to use related donor stools or unrelated, whether stool preparation should be fresh or frozen, aerobic or anaerobic (different bacteria will be present under different conditions) and whether there should there be a single dose or multiple (here).
It is possible that using antibiotics prior to transplant may be a more effective route as it will destroy much of the existing microbiome before the transplant occurs; a post-transplant diet high in soluble fibre may also improve outcomes over a normal diet (here).
Finally, there is the question over the possible presence of a so-called "super donor effect". It has been noted that some donors send many UC patients into remission, whereas other donors have a limited effect. However, it is not possible to predict who will be a super donor in advance (here). Results from studies using pooled donor stools may be stronger than those that used single donors (here). More research is needed on all of these subjects.
Helminth therapy
Although the cause of UC is disputed, one potential contributing factor is that improved sanitation in Western countries has caused a lower incidence of infection and parasitism, which in turn has caused a higher incidence of autoimmune conditions such as UC (here). The human immune system is extremely complex and without the frequent challenge from pathogens at a young age, the theory goes that it never becomes properly calibrated, increasing the probability that it malfunctions and attacks itself, as in UC. Helminths are parasitic worms, some of which live in human intestines and modulate the immune system in various ways (here). Pre-industrial humans would likely have carried multiple helminth parasites, so by adding them back, the theory is to restore normal immune function, sending UC into remission.
More Studies Are Needed
At least five randomised clinical trials of helminths in IBD (i.e. UC and Crohn's Disease) have been carried out. However, Crohn's Disease has been studied much more extensively than UC, with the author finding just two small randomised clinical trials for the latter. The first one (here) in 16 UC patients found 57% of those who received helminth therapy achieved clinical remission at week 12 vs 50% of those receiving placebo (no statistical difference). The second one (here) in 54 UC patients found that 43% of those receiving helminths recorded an improvement in disease activity at 12 weeks, vs 17% for those on placebo and this difference was statistically significant. There were no safety concerns in any of the studies the author found, It is hard to conclude much from the little data that exists, other than helminth therapy appears to be safe and may be effective in some UC patients. However, in the author's view given the difficulty in getting access to helminths and the patchy data, this alternative therapy is likely to be a long way down the list of things to consider.
4) Lifestyle Changes
Exercise
The quality of evidence concerning the impact of exercise on UC is worse than for most of the interventions above. It is, however, clear that exercise has no impact on the development of UC (here), which has been borne out by many studies. This Danish study (here) is a specific example of such a study that found no link between exercise and the risk of developing UC or Crohn's disease.
However, the evidence for the impact of exercise in extending UC remission is more mixed. One study (here) in 327 Japanese UC patients found that the most strenuous exercise was associated with a lower rate of mucosal healing but there was no relationship between exercise and clinical remission. However, another (here) in 549 UC patients in remission found that those with higher exercise levels were 24% less likely to suffer from a UC relapse at 6 months, but this was not statistically significant. In the author's opinion, if you are able to exercise, then it is likely a good idea, if not for UC benefits then for general health benefits.
On a related note, a strange finding in UC research has been that current smokers have a lower risk of developing UC (here) and that smoking may reduce the severity of disease (here), but the author cannot recommend smoking given that it hugely increases the risk of developing many other serious diseases.
Yoga / Meditation
Stress is a suspected contributor to the risk of UC relapses (here). Any activity that can help to reduce stress is therefore worth pursuing as a means of trying to extend time in remission and/or reduce the severity of relapses.
A study of mindfulness-based meditation in 57 IBD patients (here) found that at six months, UC biomarkers including faecal calprotectin and CRP were significantly reduced when compared to standard medical therapy. Another study recruited 77 UC patients in remission (here), who were allocated to either yoga or a control arm. It found that at week 24, UC activity was 1.2 points lower on the Clinical Activity Index in the yoga cohort and that this difference was statistically significant. These findings are encouraging in the author's view, though the level of benefit is relatively small.
5) Chinese Herbal Medicines
Chinese herbal medicines, or traditional Chinese medicine (TCM) has been used to treat a variety of conditions for thousands of years in China and is still in mainstream use today. Unlike Western medicine, treatments are made up of cocktails of complex ingredients, such as dried bark, herbs and roots, which contain a multitude of pharmacologically active chemicals, as opposed to a single, purified active ingredient in Western medicine. This fact makes it impossible to pinpoint the ultimate cause of any efficacy and this is one reason why most Western doctors disregard the whole practice. Multiple preclinical models (i.e. UC in mice) have shown great promise for TCM. Randomised clinical studies involving the use of TCM in UC patients are rarer, but do exist. For example, a study of 60 UC patients (here) gave all participants mesalazine and added TCM to half of these. At 8 weeks, those on mesalazone + TCM had significantly lower UC symptom scores than those who received mesalazine alone. Moreover, 43% of those on TCM + mesalazine achieved mucosal healing, vs 20% of those on mesalazine alone (this did not reach statistical significance due to the small study size).
The safety of TCM is often cited as a concern by Western doctors, as certain traditional herbs have been known to cause liver damage, especially when combined with other medicines. A systematic review of the safety of TCM (here) found that decoctions (TCM taken in liquid form) were the safest form of TCM and, as expected, adverse events were more likely when TCM is combined with Western medicines. However, there were no particularly worrying safety signals found in ~10,800 TCM-treated patients, with gastro-intestinal disorders most commonly found, such as nausea, vomiting and diarrhoea. Only around 10% of patients experienced an adverse event (6% for decoctions).
One of the problems with TCM is that it is not a regulated medical product and is therefore not subject to the same strict manufacturing standards as conventional drugs. Toxic ingredients have been discovered in TCM mixtures in the past (such as arsenic or other heavy metals). This means that the sourcing of TCM is essential, with the quality of decoctions varying enormously. Great care should be taken in selecting a highly reputable TCM practitioner (which can be very expensive) and regular blood tests should be carried out to ensure that liver biomarkers remain in normal ranges.
6) Intermittent Fasting
There are several types of intermittent fasting, which have been studied to different extents, but there is evidence that some types may reduce systemic inflammation as measured by statistically significant falls in CRP (here) and accelerate healing of damaged tissues (in mice, here). In terms of UC, some have suggested that regular bowel rest (i.e. during a fast) gives the colon a chance to recover and heal itself. While this explanation is speculative, studies have shown that intermittent fasting in mice with induced UC can significantly reduce the severity of UC (here) as well as improve gut barrier integrity and enrich the microbiome (here).
Different types of intermittent fasting include:
1. 5:2 fasting - eating normally for 5 days in a week and just 500 calories on two days (not consecutive). If your BMI is already in the healthy range and you are losing weight, you can reduce this to 6:1. On fast days, it is important to ensure that you consume plenty of vegetables, which contain few calories.
2. Time-restricted fasting - only eating during a certain window of time in the day. Most commonly, people will choose an 8-hour window during which they can eat (e.g. 9am - 5pm, or 12pm - 8pm).
3. Alternate-day fasting - eating normally every other day and restricting calories to a small number (typically between 500 and 800 calories) on the days in between. This is quite an extreme form of intermittent fasting and should not become a long-term diet.
4. Periodic fasting - a longer fast of 24+ hours, but carried out less regularly (possibly once a month).
As far as the author is aware, no randomised studies have been carried out to determine which of these types of intermittent fasting may be most effective at reducing inflammation and promoting healing (amongst other beneficial effects, such as weight loss in obese people). Moreover, no human studies have been carried out in ulcerative colitis, which is why it remains quite speculative. The author would also not recommend intermittent fasting if your body mass index (BMI) is approaching the underweight level (i.e. <18.5) as it is likely to cause further weight loss.