Know your NUCLEOTIDES - by Dr Peter Köppel and Rachel Hoyle

In this week's blog Dr Peter Köppel and Rachel Hoyle investigate the importance of nucleotide nutrition in relation to the gut...

In Japan, infant formula has been supplemented with nucleotides since 1965, but it took the rest of the world another 20 to 30 years to catch onto the concept. Supplementation of infant formula is reported to have beneficial effects on faecal microbiota, by increasing the count of ‘friendly’ bifidobacteria1, decreasing the count of enterobacteria, reducing the incidence of diarrhoea2 and modulating immune function3. 

Yet, the proportion of the population which understands the importance of dietary nucleotides – and that includes those in healthcare professions as well – is miniscule; nearly everyone with an interest in health understands the importance of macronutrients, including proteins and their composite amino acids, fats (along with healthy essential fatty acids) and carbohydrates (especially complex ones from plant-source foods). In terms of micronutrients, we’re all familiar with vitamins and minerals and more are becoming aware of the vital role played by plant compounds (phytonutrients) that act as anti-inflammatory agents, antioxidants (free radical scavengers) and also help modulate a wide range of key metabolic processes in all our body systems (for example, endocrine, immune, cardiovascular, musculoskeletal, brain/nervous system, dermis [skin, hair, nails]). But who’s ready to accept another, whole category of nutrient, namely nucleotides? We believe any person who’s spent time digesting (pun intended) the science around these nutrients will be convinced. And it’s why we feel it’s so important to get the word out far and wide. This has triggered research by us into whether nucleotides are important in adult health and if supplemental nucleotides can enhance health or prevent or treat clinical conditions. 

What are nucleotides? 

DNA is the blueprint of life and nucleotides are the building blocks of the double helix. Nucleotides consist of a nitrogen-containing base (mostly adenine, thymine, cytosine, guanine and uracil), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. FUNCTIONS Obviously, nucleotides are an integral part of the structure of DNA and RNA and are essential compounds in the energy transfer system (i.e. in ATP, NADP, NADH)4, 5, thus it has been assumed that they play an important role in carbohydrate, lipid, protein and nucleic acid metabolism3,6. It is anticipated that cells of tissues which are growing rapidly or have a high turnover rate will have a higher requirement for nucleotides, for DNA/RNA synthesis, than cells of tissues growing more slowly. Such cells include enterocytes in the gastrointestinal tract and cells of the immune system4. 

The source of nucleotides

Nucleotides can be synthesised by the body de novo from some amino acids, for example, glutamine, aspartate, glycine and formate6. Nucleotides, nucleosides, nucleic acids, bases and deoxyribose can also be salvaged from DNA and RNA degradation or from the diet and be recycled6. It appears that the intestinal mucosa, bone marrow haematopoietic cells and lymphoid tissue have a limited capacity for de novo synthesis and probably depend more heavily on the salvage pathways that supply nucleotides from the diet or from the degradation of DNA and RNA3,7. Thus, if the exogenous supply of nucleotides is low, these tissues may struggle to fulfil their need for nucleotides. 

Dietary nucleotide metabolism

Nucleotides are a normal component of the adult human diet and are ingested in the form of nucleoproteins5. Proteases and nucleases degrade nucleoproteins and nucleic acids into nucleotides; phosphatases and nucleotidases cleave the phosphate group(s) to yield nucleosides. Dietary nucleotides are not considered essential in the traditional sense because they can be synthesised by the body7. However, a number of investigators have described dietary nucleotides as conditionally essential in a variety of clinical situations and during development7,8. But it’s the intestinal tract that has the highest rate of cellular turnover in the body, this rate being greater during periods of infection or when the gut mucosa has been damaged and is in need of repair. Additionally, the 100 trillion or so microbes that make up the gut’s microbiome turn over even more rapidly, and have an insatiable requirement for nucleotides to build RNA and DNA within the nucleus of every new cell. There is approximately 1,000 times more RNA in a typical cell than DNA, most of it present as messenger (mRNA), transfer (tRNA) and ribosomal (rRNA) RNA, with the all-important mRNA comprising usually around just one to five per cent of total cellular RNA. The slides below show the cross-section of the gut, and how under ‘stress’ the villi development of an animal becomes stunted and lesions start to form. Just three weeks of nucleotide supplementation enabled the villi to grow to optimal levels (25 per cent higher), and there was improved morphology and surface area available for nutrient absorption9. Histological slides from Burrells et al. 

Are dietary nucleotides essential? 

Dietary nucleotides could theoretically become conditionally essential under three circumstances10:

• During periods of insufficient intake. 
• Where there is a high demand/high rate of growth, and 
• In the presence of disease3

It has been demonstrated that enterocytes, whilst having a high demand for nucleotides, have a low capacity for de novo synthesis8. Thus, it could be postulated that enterocytes rely more heavily on an exogenous supply of nucleotides from the diet. Further, if the dietary intake of nucleotides is low, due to a restrictive diet, these compounds could be considered conditionally essential. In a study examining the effect of a nucleotide supplement on symptoms in Irritable Bowel Syndrome, it was felt that dietary nucleotides were probably not essential in healthy people but under conditions of stress, illness or a poor diet nucleotides may well become semiessential11. 

The evidence for essentiality – do diets devoid of nucleotides cause problems? 

The supplementation of infant formula with nucleotides is considered beneficial since it has been found to influence lipid metabolism, immunity and tissue growth, development and repair12. The majority of standard infant formulas are now supplemented with nucleotides. Studies have demonstrated that babies fed nucleotide-supplemented infant formula have increased ‘friendly’ bifidobacteria counts in faeces compared to infants fed standard formula milk, but counts were still lower than found in breastfed babies13. Nucleotide supplemented formulas have also decreased the prevalence and duration of diarrhoeal disease in infants but this was not associated with changes in faecal microflora14. Thus, mechanisms other than the modification of faecal microflora, for example, effects on the immune system, might be responsible for the reduction in diarrhoeal disease. Infant studies also suggest those receiving nucleotide supplemented formula have an improved antibody response following immunisation15,16. Feeding a nucleotide supplemented diet to rats has also demonstrated gastrointestinal benefits. Rats with experimentally induced ulcerative ileitis fed nucleotide-supplemented enteral and parenteral feeds show accelerated healing of small-bowel ulcers compared with rats fed a standard formula14. In another study, weanling rats fed a nucleoside supplemented diet saw increased villus height and enhanced gut maturation compared to rats fed a standard diet17. 

Dietary nucleotides and deficiencies: where do dietary nucleotides come from? 

The short answer is, from a lot of foods that most of us eat very little of these days. The richest sources are offal meats, yeast extracts and fermented foods, such as traditionally fermented tofu, tempeh and natto (Fig. 2, below). Most plant foods contain very low levels of nucleotides (Fig. 2), with broccoli being an exception. 

Nucleotide supplementation

A number of studies examining the effects of supplemental nucleotides have also been carried out in differing populations and for different beneficial effects. Treatment by dietary nucleotides* has been shown to be beneficial for people with IBS. *Using a nucleotide supplement containing a balanced formula of pyrimidine and purine nucleotides11. A total of 37 people with IBS found that taking a nucleotide-based supplement (one 500mg capsule three times daily) resulted in a statistically significant improvement in three of seven symptom scores of IBS compared to placebo11. Namely, abdominal pain, urgency and a feeling of incomplete evacuation. Severity of diarrhoea was also improved. The improvements were modest, as would be expected in a community sample (i.e. not drawn from a clinical trial population), but no adverse side effects were reported. The authors speculate that improved gut function could be via similar mechanisms found in animal studies, namely increased mucosal protein, DNA and villus height. 

Conclusion

It is clear that nucleotides are involved in many aspects of cellular metabolism, growth and immune function. Their precise mechanism of action remains to be fully understood. The addition of nucleotides to infant formula milk and more recently to enteral food clearly demonstrates a consensus in the scientific community that nucleotides are essential for normal functioning of the body. It is accepted that dietary nucleotides are conditionally essential under conditions of immunological stress, during periods of rapid growth or insufficient intake and for disease or injury to the gastrointestinal tract. Much of this research has been carried out in animals, but there are encouraging results from human trials of enteral food, and the independent clinical studies with IBS11, URTI (colds) infections18, stress (intensive19, moderate endurance20 and resistance21). The more we understand about the roles nucleotides play – particularly in areas of the body with rapid cellular turnover rates, most notably the gut mucosa, the gut microbiome and the immune system – the more we realise that nucleotides may not just be ‘conditionally essential’, but essential for most of us, most of the time. Our high stress levels, including exercise-induced stress, along with our ever-decreasing nucleotide intake from food sources in the Western diet, and even trauma and injury, will all contribute to dramatically increasing our dietary requirement for these nutrients. 

For references, please visit www.ihcan-mag.com/References 

About the authors

Dr Peter Köppel has a PhD in Biochemistry and Immunology. He was trained in Biochemistry, with a special interest in clinical immunology, at the Institute of Virology at the University of Zürich. He then worked as a researcher in osteoarthritis and osteoporosis in a pharmaceutical company in Basel. As Managing Director of Chemoforma and Pro Bio, in Switzerland, Dr Köppel has, for over 20 years, led research and production of special nucleotide ingredients for both animal and human nutrition. This has led him to being seen as one of the world’s foremost experts on nucleotides for health and performance.

Rachel Hoyle, BSc, a science graduate, has been involved in the development of special nucleotidebased products, in collaboration with Dr Peter Köppel, since the 1990s. Her initial responsibility was to develop natural products that reduce the dependency on antibiotics in animal nutrition. More recently, Rachel has devoted her time to the research and development of nucleotide supplements for human health. Her company, Nucleotide Nutrition, now markets these products, which are all based on the Nutri-tide formula.

Exploring The Mind-Body Connection: Mood As Medicine - by Dr Lauren MacDonald

This week's blog post is by Dr Lauren MacDonald, stage IV cancer survivor who has been NED for over a year. In line with Stress Awareness Month, Lauren shares with us her exploration with the mind-body connection. 

I’ve always been fascinated by the mind, it’s what led me to study Psychology before eventually going on to study Medicine. However, during neither of my degrees did I really consider the enormity of the overlap in the two subjects – namely, that the mind has the power to help heal the body, but also make it physically diseased in the first place. I guess this is because western medicine was traditionally shaped by systems of thought that emphasised the opposite – that the mind and body are separate entities. Yet it now seems so blindingly obvious that they are in fact deeply entwined. The emerging field of psychoneuroimmunology (“psycho” for psychology; “neuro” for neurology, or nervous system; and “immunology” for immunity) is finally providing scientific support for this idea. On a personal level, I also feel as though I’ve had first-hand experience of psychoneuroimmunology via my own cancer journey.

Introducing The Mind-Body Connection

A growing body of scientific research suggests that our mind can play an important role in healing our body, as well as help us to stay healthy in the first place. Recent research has examined how emotions impact our physiology and, as you might expect, emotions such as chronic stress, loneliness, and sadness have been found to cause inflammation, hormone imbalances, impaired immunity, high blood pressure, and illnesses ranging from heart disease and cancer, to anxiety and depression. Conversely, states of calmness, mindfulness and happiness have profound positive benefits, from improved sleep and energy, to better cancer survival rates, and longer telomeres (the end pieces of DNA that shorten as we age).

Although I don’t buy into the idea that the mind can cure the body of cancer simply with positive thinking (this is something I’ve seen peddled on various cancer forums and which actually makes me really angry because it suggests the countless number of people who’ve died from this disease somehow failed to think positively enough), I do now recognise there is a significant role for thoughts and emotions in recovering from illness and preventing disease.

Stress And Cancer

I’ve always felt that I developed cancer at such a young age (and with no family history) due to experiencing two years of chronic stress prior to my diagnosis. I went through two messy relationship break-ups during that time, had to move out of my house, sofa-surfed with friends whilst revising for my medical school finals, moved into a new house with a bunch of strangers from Gumtree, and started work as a junior doctor on a busy ward. After years of flooding my body with the stress hormones cortisol and adrenaline, I was permanently exhausted, and likely put my body at risk of developing cancer. Of course, this can be debated and I’ll never know whether the chronic stress I experienced did contribute to my disease, but there is increasing scientific evidence supporting this idea.

When a person is exposed to a stressful event, their sympathetic nervous system – the system responsible for the ‘fight-or-flight’ response – is triggered, in turn increasing production of a molecule called nuclear factor kappa B (NF-kB) which regulates how our genes are expressed. NF-kB translates stress by activating genes to produce proteins called cytokines that cause inflammation at cellular level – a reaction that is useful as a short-lived fight-or-flight reaction, but if persistent leads to a higher risk of cancer, accelerated aging and disorders like depression.

The Placebo Effect: An Example Of The Mind-Body Connection

When it comes to learning about the mind-body connection and its relationship to our health, it can be difficult to choose a starting place amongst the vast and growing body of research. However, one of the best places to start is probably with the placebo effect. The placebo effect is fascinating because it unlocks the power of the mind; the biological changes observed in the body after administration of a placebo (for example a pill containing no active drug) are not triggered by the placebo itself, but rather by our mind, and our psychological response to these “fake” treatments.

The power of the placebo can be traced back to a landmark study by the late psychologist Robert Ader in the 1970’s. Ader was trying to condition taste-aversion in rats. He’d give them a saccharine drink and, at the same time, inject them with Cytoxan, a drug that suppresses the immune system, but also makes you feel sick. And it worked. The rats learned to hate the sweet drink, which they linked with nausea. Yet, when Ader kept forcing the rats to drink it, they experienced something worse than a mere distaste for saccharine. They started dropping dead, one by one. The reason? Their immune system had “learned” to fail by repeated pairing of the drink with the cytotoxic drug. Incredibly, the drink alone turned off their immunity and they succumbed to infection.

It also turns out that the placebo effect is more powerful than was once thought. In June 2017 a review of five studies, involving 260 patients, found that “open-label” placebos – those that patients know contain no active medication – can improve symptoms in a wide range of conditions.

Healing The Body By Utilising The Mind

It makes sense that if the mind can contribute to making the body sick, it can likely also support its healing. This idea is perhaps best illustrated by the emerging scientific evidence which has examined the impact mind-body activities like yoga and meditation have on human physiology. Eastern traditions of healing (Traditional Chinese Medicine originating in China, and Ayurvedic Medicine from India) have been focussed on this idea for more than 3,000 years.

Interestingly, research has revealed that people who practice activities which originated from these eastern healing systems often show a decrease in production of NF-kB and cytokines, leading to a reversal of the pro-inflammatory gene expression pattern and a reduction in the risk of inflammation-related diseases and conditions.

More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition. But this research provides an important foundation to build on to help future researchers explore the benefits of mind-body activities.

Self-Healing

Leading on from this idea, I just want to take a moment to reiterate that I am in no way suggesting that it is possible to heal yourself from cancer by channelling some kind of cosmic energy through the mind! Self-healing with regards to cancer in particular, is an incredibly controversial idea and one that as doctor I don’t believe is plausible. Many people with cancer or incurable diseases are made to feel like failures because they eat well, meditate, believe in God or divine energy, but yet can’t heal themselves. Ultimately some diseases are terminal, no matter what you think or feel. In these cases, traditional medicine (surgery, drugs or radiotherapy) provide the only potential chance of recovery, or at least a prolonged survival.

The Future Of Mind-Body Medicine

Aside from cancer, there are plenty of conditions which I believe can be healed, or even cured, by utilising the power of the mind. Non-traditional healing methods are slowly gaining acceptance within the medical world and there is finally more research being done in this area. Whereas meditation was once considered by doctors to be “mumbo jumbo”, opinion has shifted and people now understand its benefits, the science, and how it can empower patients to be active participants in their healing.

Ultimately the emerging field of Mind-Body Medicine emphasises an individuals whole being, acknowledging that emotional, mental, social, and spiritual dimensions are all important factors in wellbeing, health and healing. However, more research needs to be carried out in this area to enable medical professionals to guide patients towards potentially helpful adjunct healing modalities – rather than leaving patients to be drawn towards expensive, alternative “cures”.

In the meantime I highly recommend any activities which calm the mind, lower cortisol levels, and (hopefully) enable the body to do what its equipped to do; heal. Check out these posts for some ideas:

A Beginners Guide To Meditation

The Damage Stress Does To Your Body And What You Can Do About It

On Saturday 12th May the Yes to Life spring conference will be taking place in the China Exchange in central London entitled 'Mind your body - The vital role of the mind and the spirit in recovery and wellbeing'. It will involve talks from influential speakers in the day and practical workshops in the afternoon. 

Find out more here.

Keep calm and carry on: top tips for reducing stress - Mina Nazemi from Igennus

It is Stress Awareness Month. Stressful events can alter the level of hormones in the body and affect the immune system. For someone with a cancer diagnosis, it is vital your immune system functioning at it's best. In this week's blog, Mina from Igennus discusses ways to reduce stress through nutrition.

Finding time to relax, making sure you take at least 30 minutes of exercise five times a week, and eating a nutritionally balanced diet are all key factors for a healthy lifestyle and essential components of any stress-reduction programme.

Keep calm and carry on. If stress is unavoidable, perhaps look to diet and lifestyle factors which could help reduce the impact of stress on your body and mind.

Cortisol and stress

When faced with crisis, the body responds by releasing hormones which help prime the body accordingly.    Cortisol is well known as the ’stress hormone’ because it is released into the body in response to stress, along with other hormones such as adrenalin. The production of this ‘fight or flight’ hormone is a natural reaction to a traumatic event and, once the crisis is over, the body should return to its normal state.  Undoubtedly, cortisol is an important and helpful part of the body’s response to stress, but it is also important that the body’s relaxation response is activated so the body’s functions can return to normal following a stressful event.   In times of anxiety – financial worries, low job security, lack of sleep and so on – the body’s stress response may be activated so often that the body doesn’t always have a chance to return to normal, resulting in a state of chronic stress.

Food and cortisol

Whilst there are very few foods that can reduce cortisol on their own, maintaining an overall healthy diet with a good variety of nutrient-rich food groups can help reduce stress and regulate cortisol levels.  In general, staying away from foods that are highly processed and high in calories derived from saturated fat and refined sugar, or foods that are high in simple carbohydrates (such as refined grains, white bread, pasta and white rice) is a good move when attempting to modify the diet to reduce cortisol. These types of foods are known to increase insulin levels, leading to the release of stress hormones which can exacerbate cortisol levels.

The glycaemic index (GI) ranks carbohydrates according to their effect on blood glucose levels, and is a good guide as to which to eat more of and which to avoid or reduce. Foods high in fibre, like fruit, vegetables and whole grains, have a low GI and release their complex carbohydrates slowly, thus avoiding the sudden spike in blood sugar. Good low GI carbohydrates include high-fibre cereals, whole grain products, beans, pulses, brown rice, whole-wheat pasta, fruit and vegetables. Additionally, unrefined, unprocessed foods that are in their natural state tend to be high in vitamins and minerals such as thiamine, folate and zinc – all known to play a positive role in behaviour and mood – natural stress reducers.

What to eat

We are constantly advised to eat a healthy diet and this should be one that consists of a variety of foods from all the food groups: fat, protein and carbohydrate. These include fruit, vegetables, dairy, meat and beans, oils, and sources of ‘good’ fats.   If grains such as wheat, barley, rice and oats are included in the diet, they should be derived from whole grain foods rather than refined grains such as white flour or white rice, which are stripped of vital nutrients during processing.  Consuming a variety of fruits and vegetables of different colours, such as red, yellow or orange fruits, and dark green and orange vegetables helps to ensure you will consume a good variety of essential nutrients.

Yoghurt is a great source of calcium, and beneficial probiotics too

For dairy, try to make choices that are low in fat and choose products that are rich in calcium. Use cream and butter sparingly; although they do offer some vitamin and mineral content, their saturated fat levels means they should not be enjoyed too often! When eating meat, try to make choices that are lean such as fish, turkey or chicken. High in protein, they are excellent sources of the essential amino acids required by the body for the production of the enzymes and neurotransmitters needed to ensure we have the adequate ‘machinery’ to deal with all the body’s metabolic processes, including modulation of the stress response.

Other good sources of protein include quinoa, quorn, soya beans, chickpeas and lentils. Oily fish, as well as being high in protein and nutrients such as iron, zinc, magnesium, selenium and B-vitamins, is the richest available dietary source of important omega-3 fatty acids.  Eicosapentaenoic acid (EPA) is a particularly significant omega-3 fatty acid, as individuals who consume the highest levels (whether through direct consumption of oily fish or through supplementation of pure E-EPA oils) have been shown to have low stress levels and it is hypothesised that EPA, by directly inhibiting the over-production of cortisol,1 is responsible.

Oils are also an essential part of a healthy diet, but you should be sure that the oils are rich in mono- and polyunsaturated fat.  Both coconut oil and olive oil are good examples of healthy oils whose nutritional benefits are well documented.    Other food sources of healthy oils include nuts, olives and avocados.

Top foods for reducing stress

Oily fish

Anchovies are one of the highest sources of EPA – an omega-3 fatty acid clinically shown to reduce cortisol, making it extremely beneficial for reducing the symptoms of stress, anxiety and depression.

Red peppers

Vitamin C is utilised by the adrenal glands in the production of all of the adrenal hormones, most notably cortisol; high intake can help lower the production of stress hormones.  Most people think of oranges as a rich source of vitamin C, whereas one large red bell pepper contains around three times the amount of vitamin C found in an average orange.

Blueberries

Like peppers, blueberries are a rich source of vitamin C and often hailed as one of the top ‘superfoods’ crammed with antioxidants, which repair and protect the body from the effects of stress.  Blueberries also have the additional benefit of helping to regulate blood sugar levels, which can exacerbate stress if they fluctuate too much.

Dark leafy greens

Fill up on your greens for a B vitamin boost!

Broccoli, kale, spinach and other dark green vegetables are packed with B vitamins, known to relieve stress. Most dark leafy greens also contain folic acid, which has been proven to reduce stress, anxiety, panic and depression.

Green tea

Rich in compounds called polyphenols – powerful antioxidants that help regulate the stress response – green tea is the ideal drink for calming the nerves and reducing stress.

Stress reduction

Eating a healthy diet is paramount for maintaining long-term health and will help lower or regulate the levels of cortisol in the body.   Whether you choose to eat three meals or six smaller meals, it is important to try to include all the nutrients that your body needs at some point throughout the day.   Consuming the right foods can go a long way towards managing stress, but attention should be drawn to the detrimental effects of caffeine, alcohol, cigarettes and drugs, which can trigger cortisol production and should be avoided. In addition, attempting to reduce stress by incorporating exercise into your daily routine can lead to even better results. Taking walks, cycling and relaxation techniques such as yoga are all great stress reducers, with benefits relating to heart rate, blood pressure, and reduced levels of stress hormones.  It’s also important to find time to relax by listening to music, reading a book or perhaps taking a warm bath.

All in all, there are plenty of ways through combining diet, exercise and relaxation techniques to combat the stresses that everyday life throws at us.  Importantly, don’t stress that you are not getting it right! Ease changes into your life, so that you are happy with your choices and reap the benefits of lower stress levels.

References

1.            Jazayeri, S. et al. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry research 178, 112-5 (2010).

Evidence-based medicine viewed through binoculars? - by Robin Daly

In this week's blog post the founder of Yes to Life, Robin Daly, discusses the conflict between evidence-based medicine and patient choice. Can the two ever get along?

Listen to any news broadcast and you’ll be almost guaranteed to hear the word ‘evidence’ - usually several times. It’s the buzzword of our times and is used to try to establish credibility and trustworthiness in all walks of life.

And this is important, of course, All too often, vast amounts of effort, time and money have been wasted on initiatives for which there is no sound basis. Unfortunately, evidence is wildly variable, and often doesn’t fit the bill as a ‘sound basis’. This is notably the case in medicine, an area where, in a relatively short period, evidence has become king. A recent conference I attended, at which the word ‘evidence’ must have been up there in the top ten of all words used, prompted me to think about the nature of evidence and what really amounts to trustworthy evidence. The train of thought that resulted in this piece was prompted by a representative of NICE^[1] who said words to the effect of ‘… even including some data from patients’, as a sort of afterthought.

Our healthcare service currently has two policies that are both seen as central, but work in direct opposition to each other: evidence-based medicine (EBM) and patient choice.

EBM has inevitably become steadily more proscriptive. Despite its promising beginnings as an attempt to bring some rational basis to a largely unscientific medical system, and even though its original intention was to support clinical decision-making, in practice, medicine has become increasingly ‘cookbook’, and doctors who stray too far or often from the recipe are laying themselves open to harsh criticism or even disciplinary scrutiny.

Patient choice, on the other hand, seeks to make medicine less proscriptive. Patients often have very varied views of what constitutes good medicine, and so the spectre rears its head of a patient making a choice that fits well with their personal philosophy of healthcare, and that they would like for their own physical and mental wellbeing, but that is not considered good EBM.

This institutionalised schizophrenia has largely been overlooked, but the result is plain: EBM is being enormously successful as it is a natural extension of the ‘doctor as god’ setup that we are all too familiar with. Patient choice however, despite being on government agendas since the 1980s, and despite being enshrined in the NHS Constitution as the fourth principle that guides the NHS^[2], has made virtually no headway at all in 40 years.

How are we to make any progress with patient choice? This single issue threatens to condemn British citizens to an antiquated model of care that has more in common with the 1950s than with virtually every other aspect of our modern, consumer-centred world. The answer could lie in a re-examination of what constitutes good evidence.

As a modern consumer, I have a range of choices whenever I want to choose goods or services:

1.    I can read the manufacturer or supplier’s sales literature

2.    I can consult an ‘expert’ review

3.    I can look at the ratings of previous customers

These of course, are all in  addition to going somewhere to look at a product or talk to a supplier. But assuming, for the sake of argument, that we are buying over the internet, then we have the three forms of ‘evidence’ above to inform our choices.

Well clearly, the manufacturer / supplier is likely to do a thorough job on explaining the advantages and strengths of their offering. We may enjoy reading the sexy brochure about that fabulous new car, but it will probably tell us relatively little about the real-world experience of owning it. So, its usefulness is limited to some facts and figures.

In contrast, we traditionally turn to ‘independent experts’ for an unbiased and in-depth view of which car really is the most reliable or economic, which computer is the fastest, and so on. Experts certainly have their place and can take some of the grunt-work out of narrowing down options. But all too often,  scrutiny reveals that the ‘independent’ tag is not as watertight as we might have expected. The motivation for huge businesses to want to influence experts to be more favourable than they might otherwise be, is an obvious one, and can often result in our trusty experts being exposed to practically irresistible levels of inducement. Even if not directly influenced in this way, a ‘reviewer’ is likely to constitute a one-man-band, incorporating a host of opinions, hobby-horses, blind spots and general subjective thinking. For this to have no impact on the resulting reviews is implausible. A team of reviewers may seem a route to more objective thinking, but the power of ‘group-think’ is too well documented to be ignored.

The third option is an interesting and recent one. For certain, many of the reviewers are similarly afflicted by biased subjectivity in the way that an expert can be. But these are all people with their own real-world experience of the goods or services in question, and they’re not subject to the same levels of group-think that a team can be. If there are three reviews and one of them is a rave 5-star number, and one a complete 1-star bin job, it tells me very little. But if, as happened to me when choosing some binoculars recently - my first pair ever, and a subject I know nothing about - more than 1,200 reviewers give an average of 4.8 stars and they are the top-selling model, then that’s all I need to know.

So, what we have here is a hierarchy of evidence. EBM has its own hierarchy of evidence, but it’s quite clearly rather different.

In my consumer (read ‘patient-centred’) example -

•       No 1 is what I shall call 1950’s evidence. Its what people got back then - they probably thought it was okay, and anyway it was all there was

•       Then came along late 20th century consumerism and the rise of No 2, the ‘independent expert’. This seemed fantastic at the time, and some people still ‘believe’ in them today

•       But the 21st century is definitely the territory of No 3, the ‘consumer rating’

From my perspective, No1 is practically useless and always to be viewed with caution; No 2 can be useful, particularly when No 3 is lacking, but No 3 is the no-brainer, immediate, go-to type of evidence.^[3]

Now let’s examine the hierarchy of EBM. Right at the top, the ‘gold-standard’ of EBM is the randomised controlled trial. These are, in the main, the product of the companies that manufacture the product or deliver the service. Therefore, in my ranking as a consumer (read patient) this evidence is extremely poor.

EBM seeks to counteract some of the epic shenanigans of the pharmaceutical industry by forming bodies to regulate what choices are made by the NHS, and not to simply take the industry’s word that their products are fantastic. Well this is definitely a step in the right direction, but as in the consumer world, these ‘independent experts’ are subject to all the same forces as their consumer equivalent. Investigations have regularly exposed the levels to which the members of such regulatory bodies (and ‘trustworthy' charities) are enticed to be less than objective, how a ‘revolving-door’ exists between powerful positions in industry and in regulation (and charities) and the stark level of ‘group-think’ imposed on members. One that comes to mind, but is so accepted and so huge as to be mistaken for the very ground on which healthcare stands, is that to be even considered as a medicine capable of making people well, it’s pretty much the rule that a substance must be a patentable, new-to-nature toxin - in other words a product of the pharmaceutical industry. Tragically, all too often the regulators are clearly seen to be defending the interests of industry, rather than of the public.

As for evidence from patients, this is considered the very lowest form - merely ‘anecdotal’-  so much so that there is virtually no interest in even collecting it. Just imagine the scenario - the block-busting drug with the incredible pharma-funded trial results, given the stamp of approval by the pharma-supported regulatory body gets a 1-star rating from users who say they don’t feel any better and the side-effects are destroying their quality of life. Who will benefit from that ‘consumer’ knowledge? Why consumers of course. And what threat does such information pose? The failure to get away with a decent ‘honeymoon period’ of massive profits before everyone realises they’ve been had.

The point I’ve been trying to illustrate is that at present EBM is in direct conflict with patient choice for one simple reason: the hierarchies of industry and patient evidence are completely opposite. From where I stand as  a patient / consumer, the most trusted evidence is the least trustworthy, the least trusted, the most reliable. Is it any wonder that healthcare is failing its patients?

In one deft move, we could overcome this tragic mismatch. Healthcare could step into line with the rest of the deliverers of services and products, by changing EBM such that what patients, consumers of healthcare, have to say about a medicine or procedure is the MOST important piece of evidence - not an afterthought, or nice-to-have, feel-good extra, but one that the NHS pursues voraciously, in the interest of delivering the very best to the most patients. This way they would be living up to their constitution. Patients would benefit from knowing and receiving the most effective choices; the NHS would benefit by increasing patient satisfaction and outcomes and thereby reducing costs;  and even the apparent casualty, business, would benefit from a level playing field in which aims shift away from the almost exclusive focus on the bottom line, towards a balance between profits and patient-endorsed effectiveness.

At a single stroke (okay, maybe a bit poetic for a complete inversion of an international system!) EBM and patient choice are working together, pushing in the same direction, building better healthcare for us all.

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^[1] National Institute for Heath and Care Excellence nice.org.uk

^[2] .gov.uk/government/publications/the-nhs-constitution-for-england/the-nhs-constitution-for-england

^[3] I am ignoring the potential for dodgy dealings with consumer rating results. Although possible, it would be commercial death for any business if discovered

Let's talk cannabis - by Sue De Cesare

In this week's blog Yes to Life director, Sue De Cesare, condenses all of her learns from our recent talk on cannabis to share with us. 

Over the last year, we have heard some incredible stories of people recovering from cancer using cannabis as part of their support first-aid kit. In a lot of cases it has been used for pain management but in others for healing from the devastating effects cancer has on the body and mind.

We also know that there are 1,000’s of people with cancer and other chronic diseases taking some form of cannabis whether in the form of CBD (with and without THC) and Hemp. But the message is ‘it’s confusing’. Just by typing in cannabis and cancer, a Google search will deliver you 3,460,000 results.

So, in the UK, we are stuck – some would say between a rock and a hard place- it’s not as if you can go to your GP or Oncologist to ask their advice either.

As a charity it is important for us to bring home the facts and debunk the myths, so people feel less confused and become empowered to make decisions about their health. So, on Wednesday 21st March at the Bloomsbury Galley in London, we organised ‘Lets Talk Cannabis’. Our speakers were Dr Henry Fisher, Policy Director of Volteface (which explores alternatives to current public policy relating to drugs) and Saoirse O’Sullivan, an Associate Professor at the University of Nottingham who has spent the last 15 years researching Cannabinoids.

Dr Henry Fisher

Henry took the audience on a journey through the legal history of the use of Cannabis. Most notably, but not unsurprising, Cannabis in the UK is a Schedule 1 drug meaning it is ILLEGAL and has been lumped in the same class as cocaine and opium. It is also ONLY under UK LAW that it is illegal for medicinal use. There are a growing number of countries in Europe that have now legalised its use for medicinal purposes - find out more here. To muddy the waters a product called Sativex, which is a Medical Cannabis was placed in Schedule 4 which allows it to be prescribed as a medicine. But guess what, NICE deemed that it was not cost effective unless you have been diagnosed with Multiple Sclerosis.

It’s not all doom and gloom and there is some political will to push the agenda forward. Professor of Neurology MIKE BARNES had his review into Medicinal Cannabis published in 2016 by the All Party Parliamentary Group for Drug Reform – it concluded that there was evidence for the medical use of Cannabis. PAUL FLYNN Politician, has also been moving a Bill through Parliament to move Cannabis from Schedule 1 to Schedule 2 so that Doctors can prescribe it. It was due for a second hearing in February 2018 but has now been shunted to July – we will keep you updated as to what happens and let’s hope fillibusting will not be evident this time round. 

Finally Henry gave a short introduction to the United Patients Alliance which campaigns for the use of Medicinal Cannabis to treat chronic conditions.

Saoirse O'Sullivan

Saoirse cleared up the big question on most people’s minds...

Just what is the difference between Cannabis; Hemp, THC with or without etc….

Also, Cannabis contains many Cannabinoids – Flavonoids, Cannaflavins, Terpenes and Terpenoids to name a few – more than 80 other ‘cannabinoid’ chemicals in fact.

Tetrahydrocannabinol (THC) – constitutes the largest percentage of Cannabinoids found in Cannabis. It’s the bit that makes you feel ‘high’.

So, one of those ‘Did you Know’ Cannabis was first scientifically researched by William Brooke O’Shaughnessy back in 1839 in relation to its therapeutic effects – Cannabis was widely used for pain relief and was later replaced using Aspirin.

And, Cannabis derived drugs are being used to treat people for other conditions and in other countries. see below.

In the Press – what can we believe?

We have all read the stories about the use of Cannabis – and curing cancer. It is not our place to make comment on whether these are ‘true’ or not. What we do know is there is sufficient pre-clinical evidence (all in vitro and animal research) of anti-tumoral benefits.

• Cannabinoids kill cancer cells

• Cannabinoids slow cancer cell growth

• Cannabinoids reduce new vessel growth

There is also sufficient evidence to show that the use of Cannabis for symptom management does help with:

• Nausea 
• Appetite
• Weight maintenance
• Pain
• Sleep
• Mood
• Depression
• Quality of life

So as individuals we must make our minds up about what steps we take. There are some positive things to do – get involved. Join the United Patients Alliance; have a look at what Carol Coombes OBE is up to; document your own evidence if you are using Cannabis and let us know the outcomes; keep an eye on what’s happening with Paul Flynn’s Bill as we will; if you have an open relationship with your health team (GP, Oncologist, practitioner) get their view.

As the talk was oversubscribed we will be holding further events on this subject. The next one will take place in Manchester and we will aim to do another one in the UK. Please do get in touch by emailing office@yestolife.org.uk if you are interested and we will aim to organise more across the UK.