There’s no such thing as bad weather… only the wrong clothes

Yes to Life Interview – Spring Congress 2021 – Dawn Waldron and Robin Daly

Talk Description

Based on Billy Connolly’s insightful observation, Dawn and Robin will explore the idea that poor diet and lifestyle choices are the most important factor in fending off carcinogens. Referencing Michael Fenech’s work on the ’nutriome’ which shows that micronutrient deficiencies and macronutrient imbalances are major causes of genomic instability – one of the recognised hallmarks of cancer, rivalling the impact of X-rays. The discussion will look at how we can better protect ourselves against our toxic inner and outer world.

It’s widely recognised that cancer diagnosis is more common following periods of intense life pressure that leaves us depleted physically and emotionally: a perfect storm. Dawn will explore how diet and lifestyle choices impact gene stability and gene expression, highlighting the potential for Nutrigenetics to provide personalised nutrition protocols to support treatment and recovery. By understanding our own ‘nutriome’ – the precise amount of essential nutrients required for optimal genetic health – we can improve our ability to protect ourselves against the elements. 

INTERVIEW CONTENT

Robin: So the first thing is to explain: exactly what this has got to do with Nutritional Science and Cancer.

Dawn: I’ve been following the work of Michael Fenech, a molecular biologist in Australia. His career has focussed on DNA damage prevention. He has spent the last couple of decades looking at interactions between diet and genes and, in particular, looking at the things that damage our DNA, genotoxins. His most recent paper was about the role of nutrition in DNA damage and repair and he highlighted a key point:

That micronutrient deficiency (or excess) can cause DNA damage of the same order of magnitude – if not greater – than the DNA damage caused by significant exposure to environmental genotoxins such as chemical carcinogens, ultraviolet radiation and ionising radiation. 

For me that was one of those moments when my whole appreciation of the importance of nutrition evolved. 

I mean, we all know about the things that cause cancer – X-rays, pollution, smoking, pesticides, too much sunshine, etc – and we try to avoid them. But the idea that having a bad diet is just as much of a problem for DNA damage – to the same degree – is new. 

Moreover, in his research he highlights what we call the dose response curve. This is the idea that too much can be as damaging as too little. When you plot results on a graph it creates a U-shaped curve with optimal results in the middle. That’s something we need to be keenly aware of. 

In his research, Fenech is looking at diet not supplementation and he highlights the problems with excess food and nutrients: something I’ve felt instinctively for a long time – that the tendency to hyperdose nutrients and hypereat superfoods may be harmful too. Giving supra-physiological doses of nutrients may cause problems. You may have come across this in relation to Vitamin C. In small doses it’s helpful, in very high doses it can be cytotoxic. Another way of expressing this is the well-known phrase, ‘The Dose Makes the Poison’, attributed to Paracelsus who states that everything, even water, can be toxic in the right (or wrong) amounts. There is no evidence that cancer outcomes can be changed by megadosing and here is a clear indication that the opposite may be true. 

What Fenech has shown us is that diet is vitally important for cancer formation and development – and he has shown us why. 

It also indicates that, nutritionally, we need to stay within physiological limits – but it can be hard to know what these are on an individual basis.

That’s where nutrigenetics can help.  

Robin: So this is a very different picture to the ‘it’s just bad luck’ story that incredibly got a lot more airtime than it deserved a few years ago – largely I suspect because the people saying it were important enough to know better. The thing that’s so strikingly different between the two views is the position it puts us in: powerless victims of fate, or empowered contributors to our own wellbeing. At the end of the day though, it’s not about picking a picture we like or that makes us feel good, it’s about what’s true. So would you make the case for the contribution of nutrition and lifestyle to our genomic stability, to our ability to avoid malignancy?

Yes I would. And I think this research strongly supports that stance. There is an element of bad luck too. Fenech isn’t ruling out the role of environmental toxins, or genotoxins, but he is saying that diet is equally important. 

We are used to hearing that diet and lifestyle choice are responsible for 30-40% of cancers (and even this strongly tends towards obviously damaging lifestyle choices like smoking and alcohol) but I think this research fundamentally undermines that estimate. It holds out the possibility that ALL cancers are influenced by diet and lifestyle choices. If your cells are not properly protected with nutrients then they are at risk of genome damage – independent of other environmental pressures.

In fact, it begs the question, ‘’If your cells are adequately nourished, are carcinogens such a big issue?”

It’s important that this doesn’t come across as a ‘blame’ thing because emerging in parallel with the insights provided by Fenech is the idea that we all have significantly different nutrient requirements based on our genes and, more specifically, our gene variants called single nucleotide polymorphisms (SNPs).

Robin: How so?

Fenech proposes the idea of the nutriome – a term which I think we are going to hear more often. It’s defined as “the precise combination of nutrients and their doses that optimises genome stability” and it’s different for everyone. He maintains that we urgently need to move to a genome-led model of nutrient levels. That it makes much more sense than the current RDA system, designed to prevent deficiency diseases rather than promote optimal performance, and based on outdated ideas and observations. 

In many ways RDA has been successful as a preventive tool – you don’t see many people with scurvy and rickets these days. But RDAs were first set in 1943: we need a new basis and new measures for diseases of the 21st century. 

Fenech says it is already within our capability to do that – and to design dietary patterns to deliver that level of nutrition. He introduces and validates the idea that individuals may need more or less of a particular nutrient NOT ONLY BECAUSE OF THEIR DIET AND ENVIRONMENT BUT ALSO BECAUSE OF THEIR GENOME. 

This seems to me to be key – especially for cancer patients. We are increasingly understanding the concept of ‘At Risk’ groups but consistently failing to link it to nutrition and lifestyle – or at least in a preventive way. The at risk groups identified for diseases like COVID and CANCER are associated with nutrient depletion, and this is more significant for some people than others.

Crucially, everyone’s nutriome will be different – your nutriome is different from my nutriome. It’s a personal calculation based on your genome. So, instead of a one size fits all daily dose that, for example, recommends 60mg of Vitamin C – a dose that is wholly inadequate in the modern world, even for normal people, never mind people with SNPs that impact Vitamin C levels – we will move to a one size fits one daily dose. And it’s important to note that your nutriome will differ dependent on your environment. On a stressful day, for example, you will need more magnesium. Something I flag with my clients in relation to their lifestyles: our nutrient requirements change with our diet, our stress levels, our environment and our genes. They change on a daily basis – when we go on holiday, or for a job interview – and our diets change too.

At its most basic level, nutrigenomics allows cancer therapists to support clients more safely by understanding their basic and differing nutrient requirements. It can help us understand where there’s a fundamental need for supplementation, and what molecular form that supplement should take. Something that can be particularly important during treatment. 

It gets a lot more exciting than that but that’s a great starting point.

Robin: Now can we compare and contrast the notions of inherited genes that define our fate, with inherited tendencies. These are not the same thing are they?

Exactly! In fact that’s what nutrigenetics is all about. It’s a subset of epigenetics that looks at the way eating different foods changes your gene expression.

BRCA is a good example, a good place to start. 

People often tell me that they have the BRCA gene. 

Well, actually, we all do. 

Everyone has two copies of the BRCA1 and BRCA2 genes: one copy inherited from their mum and one from their dad. 

You only have an increased risk of breast cancer if you have inherited a BRCA1 mutation – i.e. a damaged copy of the BRCA gene. And you are more likely to go on to get cancer if the ‘good’ copy gets damaged which is an argument that brings us full circle but that’s a story for another time. Not everyone who carries the BRCA gene gets cancer, and we think that people’s diet and lifestyle choices are involved in making the difference. 

The point is that we all have the same genes but some of us have different variants of those genes.

And those genes are impacted by the diet and environment we choose. 

A good analogy is a piano keyboard. The same notes can be used to play a different tune depending on whether Oscar Peterson or Arthur Rubinstein is at the keyboard – or even Les Dawson. (You may need to look at YouTube to understand that one.)

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Nutrigenetics looks at variants called Single Nucleotide Polymorphisms where just one base pair in a DNA molecule is altered. These polymorphisms, normally called SNPs for short, impact the way we handle nutrients, absorption, activation, transport, recycling etc. Some SNPs can impact nutrient activity by as much as 10x – significantly affecting the amount of a nutrient we need. Some SNPs affect absorption or conversion to the active form so we may have to leapfrog metabolic pathways. 

So, to take the analogy further you might have a note on the piano that is out of tune, or a dud key that doesn’t play the note properly. You have to be familiar with the instrument to know how to compensate for that. 

Robin: So let’s recap… how does all this relate to the opening quote?

Fenech’s research is a real game changer. It got me thinking… are we looking at it the wrong way round?

Are we too focussed on the damage and not enough on the repair? We talk about carcinogens, the things that cause cancer…  alcohol, smoking, X-rays, Tamoxifen, shift work, — all the time. What if there’s no such thing as a carcinogen if your cells are well protected? 

Maybe it’s more about the nutrients than the carginogens? 

So if carcinogens are the weather, the quality of our diet is our protective clothing. 

It’s like the sunshine paradox.

Robin: What do you mean by that?

Well, we know we need sunshine, it’s vital for all life on the planet, but we have now classed it as a carcinogen. We are frequently told that sunshine causes skin damage. But Fenech’s research suggests it only happens because our cells are not working as well as they should be. They are not nutritionally protected – inflammatory and oxidative pressure is already high so the oxidative stress caused by sunlight – that we badly need – makes it dangerous. So sunshine becomes a cancer-causing problem, not a cancer-curing one.

So we avoid the sunlight.

So our vitamin D plummets.

So we get breast cancer. 

A vicious circle. 

If you combine that with low Vitamin D receptor expression and poor transport you have an even higher risk group. 

We can go on and on avoiding nature and staying indoors. 

Or we can improve our nutrient status that allows us to remain healthy without getting damaged by our environment. 

But it takes a paradigm shift to think that way. Even for those of us working in integrative medicine. And people with SNPs need to know this sooner rather than later. 

Robin: OK – now it’s time to start looking at the implications of all this for the way we live. Can we start off by looking at the prevention aspects. I’m guessing that, with the rise in personalised data, prevention can now be divided into things that could be said to be generally good for anyone, and things that are specific to individuals based on their genetic makeup?

That’s the big question. We need to understand ourselves better. Why do some people smoke 40 a day for life and live to be 90 and some people eat mountains of broccoli and get cancer?

Currently the prevailing view in science appears to be about shielding ourselves – avoiding risk – whether we’re talking viruses or cancer. And then trying to mend the damage with medicine. 

Is the planet suddenly more hostile? Or are we simply under-armoured… undernourished?

Fenech’s research identifies the nutrients involved in protecting the genome.

The usual suspects: 

Vitamins: B2, B3, B6, B9, B12, C, E, 

Minerals: Calcium, Magnesium, Iron, Selenium and Zinc. 

And once again, beta-carotene delivers some sensitive results, with highest levels associated with more damage – which may have something to do with the high prevalance of SNPs on our Vitamin A conversion genes. 

It’s no surprise that the methylation nutrients are in there, the co-factors for some of the body’s most important reactions. Fenech’s particularly interested in the role of nutrition in DNA replication, protection and repair. He has published a whole paper on the role of folate (Vitamin B9) and vitamin B12 in the maintenance of the nuclear and mitochondrial genome. Folate deficiency is directly associated with chromosomal damage and mitochondrial DNA damage – a mechanism that is targeted in chemotherapy. The vital importance of these nutrients for long term health, the overall poor quality of the average diet, the tendency to make diet choices to protect the planet without understanding the risk to ourselves means that   everyone is at risk in this situation. We are all exposed to environmental damage and nutrient deficiencies – but for some people it’s more dangerous than others. Nutrigenetics can help us identify that and do something about it. 

So granny was right when she told us to eat our greens. But even that is not enough for everyone. When we look more closely at the nutrigenetics some of us need extra help absorbing folate – which means optimal health may require a supplement, if we want to live a normal life. 

We need folate, B12, magnesium, zinc and iron for nucleotide synthesis, DNA replication, methylation and chromosome stability. We need enough antioxidant nutrients – Vitamin C, E, zinc, manganese, selenium – to prevent DNA oxidation.  And we need plenty of niacin, zinc, iron and magnesium for DNA damage sensing and repair. 

Deficiency of any of these nutrients puts stress on the replication and repair mechanisms leaving us open to DNA damage. It increases the risk of damage from internal and external toxins. And disables normal control of gene expression. Protein deficiency and excess calorie intake are also associated with higher levels of DNA damage. 

So what Fenech is saying is that if we can get our diets right we can prevent a lot of DNA damage associated with developmental and degenerative disease.  

And what I’m saying is that nutrigenetics can help you do that in a more personalised way, which may be important for cancer patients. 

It’s a circular argument, nutrients affect gene expression and gene health, and that in turn affects your nutrient requirement. 

And nutrigenetic panels are a good place to start investigating these nutrients for yourself. 

Robin: How does this change our thinking?

We are used to thinking of DNA damage in terms of oxidative stress and inflammation and unquenched free radicals – and external sources like pollution, radiation etc. And we are used to thinking that this is the primary and uncontrollable cause of cancer. But Fenech is saying that diet is just as important. 

It may even be that if our diet is good enough, the impact of environmental toxins can be reduced, less random, not so much down to luck. Eating the right diet is one of the most important ways to protect our DNA. And some of the accidents we blame on radiation, or mobile phones, or EMFs may be more about what we’re eating. It’s similar to the idea that a strong immune system can protect us from getting a virus. 

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There’s an apocryphal story that Louis Pasteur regretted that he spent his life focussing on the germs and not on our natural ability to counteract them. Having spent all his life focussing on external microbes, he realised he woulda shoulda coulda been focussing on how humans repel them. i.e. how to make the human body stronger, not how to fight the monster. Similarly, we spend our lives focussed on the processes that cause cancer, not on the processes that protect us. And maybe that’s the wrong way round.  

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And nutrigenetics provides that deeper level of understanding, realising that we may have genetic variants that make protecting our DNA more difficult for me than for you. 

BINGO! That’s the shift. That’s where we start to leave bad luck and inevitability behind and start to understand that it’s not random but personal. 

DNA damage is closely associated with cancer. We can debate whether or not it’s the chicken or the egg but it is involved in the process. Understanding DNA damage as a nutrient deficiency fits very neatly with our aim to think about the terrain rather than the tumour. It’s about supporting the microenvironment – and it underlines the need for us to understand our own genome asap. Especially those of us with chronic health issues. It may even become relevant for preventing some of the mutations within tumours, but that’s another subject. 

Robin: How do you use this in practice?

When dealing with something as sensitive as cancer it makes sense to measure anything we can. But for as long as cancer outcomes are random we know we’re not measuring the right things. 

Tumour shrinkage does not correlate with survival, but neither does serum B12. Circulating tumour cells do not necessarily tell us about the severity of your disease; and even chemosensitivity testing becomes obsolete as tumours evolve. Receptor status can change as disease progresses, tumour markers are treated with suspicion by oncologists and Oncotype testing is only a rough guide based on some very general statistics. Of course, we can look at cellular metabolism pathways but we know that cancer cells are the ultimate genetic shape-shifters so any treatments that target individual pathways are likely to expire. 

We still have a lot to learn.  

In my view – frustrating though it is – there are no cancer metrics that reliably predict survival.

So – for me – the science of nutrigenetics provides another way in – a useful jumping off point – and a way to be more personal.

It’s not only useful to help us prevent DNA damage, we can clearly relate it to body systems and to the tumour microenvironment and known risk factors. It helps to identify and explain your weaknesses. For example, glucose management, oestrogen issues, inflammatory tendencies, antioxidant status. 

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Reflecting on an article in The Times this week:

A team of researchers in The Netherlands headed by Mathilde Almekinders, have discovered that the size of adjacent fat cells predicts progression of DCIS via COX-2 expression, and that treatment decisions can be based on this finding. 

COX2 is a well-researched inflammatory marker linked to prostaglandin pathways.  

Diet and lifestyle factors influence COX2 expression. 

The FADS2 SNP can exacerbate COX2. 

So, as we become clearer about issues like these, as we understand more and more about cancer cell behaviour and the conditions in the microenvironment, it will become increasingly helpful to know if we have related SNPs.

Full research article at https://www.nature.com/articles/s41523-021-00232-w

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Nutrigenetics can also help with treatment decisions – tailoring treatment to patients – predicting:

pharmacokinetics and dynamics

drug resistance

chemo response

potential toxicity

antioxidant levels

drug effectiveness (e.g. Tamoxifen)

If you’re talking precision medicine it doesn’t get more personal than this.

Robin: It’s beginning to sound as though our genomic profile is something we would be unwise to ignore nowadays. With 50% of the population due to get cancer at some time, we really need some reliable indicators to point to the precautions we could personally be taking in order to stay on the right side of that 50%. Is genomic testing becoming a must these days?

I’m reminded of a client who recently got in touch. She explained her diagnosis to me and told me that she has always done everything she can to be healthy. Followed by, “But I guess healthy doesn’t cut it?”

To me nutrigenetics is the key that fits that lock. Nutrigenetics shows us the extra things we need to do because of our genome.

In cancer we’re used to thinking about super-foods and super-health, but this is a different way of looking at it. It’s supra-health – an extra layer of health that is personal to you. 

But we need to be cautious about how we get our information. Although genetics is something that we think of as very certain epigenetics shows us that it’s not. First of all you need to know that the test itself is being carried out by a reputable lab. And that the person looking at the research reporting the significance of the SNP knows what they’re doing. One of the key, and perhaps underrated, skills is the ability to select clinically relevant genes from the mountains of research out there. That’s why I’ve chosen to team up with Emma Beswick at Lifecode Gx who takes a very rigorous look at this area – and provides excellent practitioner support. 

Then we need to understand that, while DNA tests are highly personalised, they are still looking at the whole population rather than the subset of the population that has cancer. So the way I work is to make links between the evidence for cancer and the evidence for SNPs and make links between the findings to draw conclusions for nutritional protocols. In my view, generic online DNA tests are limited in their value because they are taking this broad view rather than being concerned with cancer.

In fact, Emma and I are currently devising a Cancer-oriented nutrigenetic panel for Lifecode Gx which we hope to make available fairly shortly. 

Robin: It’s not so long ago that Nutritional Therapists worked largely on intuition and clinical experience, when it came to tailoring support for an individual. Then, along came an ever-increasing raft of tests that started to provide personalised information that enabled the jump from ‘people with cancer generally need…’ to ‘this person needs…’ The last thing I wanted to ask about is the effect this gene-level information is having on the ability of Nutritional Therapists to prescribe measures that successfully support health and wellbeing.

I like to use nutrigenetic panels alongside functional testing for validation. Nutrigenetics can reveal a tendency but functional testing can tell you what’s actually happening, so the two can back each other up. I’ve had patients with a worrying selection of SNPs but an excellent DUTCH test because they’re doing everything right. And I’ve had patients with a worrying DUTCH test where nutrigenetics helps me to put it right. 

What this type of testing helps with is pinpointing which pathways to target. You may have all the symptoms of excess oestrogen but nutrigenetics will tell me why. Is it aromatase upregulation, or are you making too much 16-OH, or are your Phase 2 pathways blocked, or maybe glucuronidation is causing oestrogen recirculation? You can make a more accurate assessment of the situation. 

You can also look at related genes like the COMT gene – which detoxifies oestrogen and adrenaline and may be slow – or caffeine genes which may be impacting aromatase, COMT and adrenaline. It’s often this combination of SNPs that gives the biggest insight. 

Robin: How does this translate into the way you practice?

I worry that, as this subject becomes more and more technical, it can be hard to find any clarity – that’s just as true for me as it is for clients. Sometimes it can be hard to see the wood for the trees. 

I remember when I was diagnosed, 23 years ago, the most helpful thing my wonderful surgeon did for me was explain that he had removed my tumour with clear margins. Age 33 I didn’t understand anything about cancer but I could understand that, and I could picture it, and I could hold on to it. Somehow it made me feel secure that he’d got it all. A clear before and after picture. In clinic I try to help clients feel the same way. 

In essence, no matter how much science we apply to our work we have to make a big enough difference for the cancer to go away. We have to radically change the terrain in favour of healthy cells and away from cancer cells. And we have to do it in ways that clients can feel, and hold on to, and visualise. In a way that makes them feel safer. 

So you can look at all sorts of things

Stress

Sleep

Alcohol

Exercise

Oxygen

Diet

And you can look at how you’ve changed your diet and lifestyle to suit your genes.

And you can feel good about that. It’s powerful stuff. 

In the past 100 years two things have changed: the environment has become a lot more aggressive, and our cells have become a lot more depleted.

Only one of those is really within our control.

Nutrigenetics can show you how to change it for the better.

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Reference: Michael Fenech (2020) Chapter 4. The Role of Nutrition in DNA Replication, DNA Damage Prevention and DNA Repair. Principles of Nutrigenetics and Nutrigenomics. Elsevier Science. Kindle Edition. 

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Image: In February 2006 we flew to New York for a family break and as we arrived the first snow flakes started to gently fall across the city. By morning a record 27 inches of snow had fallen in Central Park and the city declared a state of emergency. We hadn’t come prepared for quite such extreme weather (it was almost over my head!!) but we bought some plastic bags from the corner shop to wear INSIDE our boots to keep our feet warm and dry and we saw the city completely quiet – a treat that few people can ever have experienced – walking down the middle of Fifth Avenue with barely a car in sight – and some people still braving their stiletto heels!