The role of Metabolomics and big data in nutritional science

Nutrition has its roots firmly embedded in history. Early observations of how what we ate affected serious conditions like scurvy and rickets, were noted even at the beginning of the 19th century. It was quoted that the existence of organic nutrients was required only in small amounts to prevent disease.

Prolific research completed by the early 20th century had identified various ‘vitamines’ and by 1933 alone, 1000’s of papers had been published, 300 on vitamin D alone.

The dose makes the poison

Fast forward to the ’90s and studies on what constituted as the right intake of vitamins and minerals for humans were based on either people not becoming ill and even more animal studies. Lots of science, but also lots of disagreement.

All organic compounds can be lethal, but at what dose does it make it so? The middle ground of what makes us sick was an even greyer area.

The final recommended requirements for humans covers just 13 vitamins and 14 minerals. Laid out in the early ’90s and only recently updated, the values are sometimes wildly different when comparing the UK and US figures. The UK’s vitamin D levels were half the amount stated for the US, although the UK National Health Service now reflects the UK after a 2016 report.

As data is gathered, discussion and panels work through slowly adjusting their conservative advice, much of the community reacting even slower. The amount of variation on advice is bordering on the extreme. Some doctors, sharing their views in the tabloid press, which of course gets amplified further by unqualified journalists. Often the views on vitamin supplements is “throw them in the bin!” and “you pee most of them out so what’s the point?” they’re useless right? 

As individuals, how do we know if we are deficient? What vitamins do our body’s use or even need when taking supplements? If we want to prevent illness, putting dietary advice aside, these should be some of the questions asked. In the UK we can not simply pop into our local general practitioner (GP) and ask for a B12 serum test, you will need to be suffering some sort of noticeable symptom, not a hunch based on browsing the online forums.

It’s good to be cautious 

There are plenty of studies showing negative results when taking vitamins either at the wrong time or in the wrong doses. For example, if you are a smoker, taking vitamin A, is certainly is not a good idea says the research. Unfortunately, these studies are also used to scare people into a state of confusion pushing the problem the wrong way.

A problem now being felt across the world. Vitamin D levels are said to be deficient across all populations, in a 2013 report, estimated to be upwards of 1 billion people globally, even in warmer climates. We spend so much time working and living inside our homes and offices, we do not get the same amount of sun that relatives used to, let alone our evolved ancestors.

Yet the subject is selectively reported in the mainstream news. No one can agree, experts argue at the maintenance level for a healthy individual, often not taking in to account the melatonin levels already in the skin and the genetic variations of individuals. How can our ‘official guidelines’ be useful? Considering the hormone, vitamin D, can affect the expression of hundreds of genes, I would have thought this would be considered a serious problem and something that health official should be trying to fix.

Vitamins aside. We are all unique and need individual assessment.

Factors involved in the diagnosis of disease

Depending on which specialist you see, and there are many recognised professional disciplines (as well as the unrecognised), a diagnosis and treatment will be decided based on if you are looking to stop a symptom in its tracks or find the root cause, you may very well arrive at two totally different results. Not an ideal situation.

Clearly, there are some cases of vitamin or mineral deficiency that overlap in their symptoms but result in a myriad of different metabolic problems and disease. 

As someone who is suffering, who do you turn to for advice? our first point of call is usually our local GP or hospital.

Some of us may turn to Google for a second opinion, many medical professionals do their best though to add doubt and confusion, with conflicting information published in blogs and books. With government regulations deciding differently from one another. Something is a little misaligned to put it simply.

We don’t know what we don’t know goes the famous quote. And to be honest, the majority of us underestimate what we really don’t know about the science of food and how it affects us each individually. Because we are undoubtedly, individuals, all slightly different, whether it be via our genetics, our unique and complex microbiota or even the environments we have been exposed to. These all affect us in varied, and often extreme ways even when being compared to our close family members, including surprising results from genetic twin studies and their microbiomes.

Vitamins and metabolites collide

Understanding why these differences occur is just one of the many mysteries being unfolded today. But to solve these questions takes serious amounts of resources, data and a completely different approach to the slow step by step, study by study approach used by conventional research methods.

Metabolomics and the study of the human metabolome (not to be confused with the microbiome), is but one method of tackling this grand project. Heralded as a partner tool to the vision of precision and preventative medicine, Metabolomics is defined as “the large scale study of chemical processes involving metabolites, small molecule substrates, intermediates and products of metabolism” and the metabolome “represents the complete set of metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes”.

Put simply, its the study of very very tiny molecules that are required or are a byproduct during the metabolism of a cell or organism. The human metabolome is focused on finding out every single molecule residing in the human body. Examples might be the usual proteins, amino acids, lipids, antioxidants and of course, vitamins and minerals to name but a few, but it’s complexity resides in the fact, that it involves everything, known and unknown to do with cell metabolism.

What’s the ‘matter’ with the food metabolome

Metabolomics covers many different scientific disciplines, the area that is primarily focused on what we eat and how it affects us is Food metabolism, or the study of all molecules found in the food and plants that we eat. This is called the ‘Food Metabolome’.

Food metabolomics is driving the analysis of all plant compounds of which the size of the challenge is staggering. A non-profit database funded by the Canadian government FoodDB.ca now has a growing list of a quoted 28,000 compounds (although this is now severalfold higher). This is a far cry from the USDA’s (The National Nutrient Database for Standard Reference, maintained by the US Department of Agriculture). With an entry like raw garlic showing 60 plus nutritional compounds whereas FoodDb, lists over 2000.

Take our humble Gingerol compound from our favourite rhizome Ginger. The USDA has an entry for raw ginger here which will return 62 rows of data showing a comprehensive list of macronutrients, vitamins and amino acids. Gingerol is not on the list.

Shed light on the darkness

FoodDb is only one database, there are many others, and growing as they often share and cross-link each other’s data. The power of open sourcing data is really driving new discoveries. It is noted that we have only discovered a fraction of the total known compounds produced by nature and all its interactions, quotes in the many millions is bounded about. 

The idea is we have only identified less than 1% of these compounds and have no idea what they do and how they affect our health. That leaves 99% of unknown nutritional molecules and their interactions. This has been coined as the ‘dark matter of nutrition’. Our own human biology is influenced by these 10’s of thousands of compounds are chemically transformed by enzymes throughout our bodies, from our mouth to our gut microbiota. The result is even further complexity resulting in even smaller metabolites that recirculate throughout our blood and tissue.

The discovery is to find out what they are and what they are doing. It’s a very big undertaking.

Precision nutrition and drug discovery

The power in these new databases is identifying the compounds in what we eat and how it affects our health. These databases are often cross-linked with the other ‘omics’, genomics for example, how our genetics and the expression of our genes affect human health and disease.

We used to think much of our genes were just junk, but as the data was collected we know that not to be true. Much of our genes can indicate a susceptibility of certain diseases, although its not a given, it can often be just down to how our genes are expressed (epigenetics), or turned and on and off. And we are now learning this is done in so many ways, nutrition is just one, but plays an enormous part.

Our bodies are constantly trying to stay in homeostasis and very often one of our switches is turned on or off in the wrong direction with a cascading effect. One job of metabolomics is to answer, what are the interactions with food that may produce a positive or indeed a negative effect. How can we be more preventative as opposed to the current course of reactive medicine?

Currently, the power of this science is being used by many pharmaceutical companies to discover new drugs. Even drugs for cancer often have their roots in natural plant compounds. It can be one of the benefits. But wouldn’t it be nicer if we could use those benefits found in plants before cancer occurs. A much more powerful result.

The irony that we are now crossing over, from chemicals found only in plants and only used by ‘alternative medicine’ to all of sudden being isolated and used in the treatment of serious illness and disease. Of course, until something is ‘proven’, it is classed as mere quackery. Even if thousands of people may note a benefit. It then slowly becomes part of mainstream medicine and accepted.

Ai, big data and our own unique nutritional plan

A huge industry of tech has emerged to take part in this new era of discovery. From mass spectrometry and the analysis of chemical compounds to the analysis of the data and the job of finding the patterns across so many databases.

Partly known for its success in identifying how genetics play a role in whether we are more likely to become diabetic or to develop dementia, for example with the APOE gene (apolipoprotein E) and its potential association with Alzheimer disease when referenced across millions of individual genetical profiles.

Given the challenge to plough through not just genetics but, metabolic pathways, metabolomics and associated published studies. It is the grand prize to uncover so many missing parts of our jigsaw and answer questions that have eluded us for centuries.

We now understand how cooking food alters the chemical composition, the presence of the carcinogenic compounds like acrylamide, when some foods are heated for example. We do not, however, know very much else about the impact of processing on the other thousands of chemicals found in our food.

Using machine learning and artificial intelligence to unveil nutritional dark matter will help us to understand ways in which reducing our bad habits and treatment of food known to harm us, at least in the long run. Plus, eating the right foods based on our own genetics, current health and environmental factors could create our own unique and precision nutrition guidelines.

Tracking the deep data in food, science research and matching it with our individual genetic variations and health history, might just lead to real nutritional plans that improve our health.

Discussion

I wrote this article with an understanding that our current knowledge of health and nutrition is only based on what we can possibly know right now. That said, our current nutritional guidelines are based on conservative research, often decades old. It certainly is not ‘current’ research. 

Therein lies a problem, as we have witnessed with a growing catastrophe of avoidable disease with simple nutritional deficiencies being ignored, basic low hanging fruit, which only comes to light when we experience major pandemics and the effects on our weakened immune systems. 

As we accelerate through the dark matter of nutrition and begin unravelling the answers to what truly keeps us healthy and improves our longevity, based on our own unique genetic profiles. How long will it take for mainstream medical professions and namely governments who have a duty of safety to their citizens, to manage this stream of new information as it comes online? Will politics get in the way as people blame their governments for acting too slowly with this new health data and advice. 

We, humans, are such complex creatures, we are plagued with government-approved treatments and food additives, health fads and foods, that only the test of time reveals that they were not as safe as we once thought. That’s our dilemma. Big pharma and the supplement industry will drive that testing as fast as possible and leave us as the global guinea pigs.

For the most part, I foresee the advice will continue to be, ‘eat real food not processed’ more plants, fibre and less animal protein and fats. What will change is what is the best natural food you should be eating based on your genetics and what should your own unique healthy microbiome look like based on those genetics.

We need to acknowledge that if inflammation is one key cause of disease, then part of the problem is still a lack of key vitamins and minerals in our diets and our lack of understanding of those thousands of phytonutrients that are proving to help reverse that. We seem to have swept this problem aside as something that we got rid of with scurvy and rickets.

The vitamin D problem? is this because our governments have a set period of time-based on social pressure to address it? Or is it because they are realising that simply fortifying our processed foods is not the answer and are not sure how to fully address the problem!

Personalised and precision nutrition is certainly an exciting prospect, as we shed light on the ‘dark matter’ of literally millions of natural compounds, biological pathways and environmental factors that interact and decide if we become ill or live to become a centenarian. 

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