Know thyself.

Got a question you want answered in a hurry? Checkout the FAQ.

Sex, it turns out, is really good for us.

Umm, okay that came out wrong, what I meant to say was that sexual reproduction is very good for the human race.

Thanks to sexual reproduction and genetic recombination almost all of us are genetically unique.

This is great for our species. One of the advantages of sexual reproduction is that genetic variation provides a pool of potential solutions to problems that we, as a species, haven’t encountered yet.

If a new pathogen, or some other challenge, comes along, genetic variation means some of us will likely survive to continue the species.

When it comes to medicine though, this genetic variation is a bit of a nuisance.

Just as genetic variation enables different people to react differently to pathogens, it also makes them react differently to different treatments and drugs.

This is what makes getting approval for a new drug so difficult. Testing on a hundred people doesn’t give you any idea if, among the billions of humans, it’s going to harm some people with a specific genetic makeup.

Even if it only harms 0.1% of people, that’s still 8 million people worldwide. Drugs like thalidomide, mercaptopurine, clopidogrel and even codeine have all taught us the truth of this.

Genetic variation also makes it hard for scientists studying how diet affects our health and well-being.

How can you make generalised dietary recommendations when we aren’t sure that everyone will react to that advice the same way? Does a particular dietary habit cause illness in all people or is it just a subset of people with a specific genetic makeup?

How can that annoying friend, that we all have, live on hamburgers and doughnuts without putting on weight?

Vitamin D as a Case Study in Human Genetic Variation

Vitamin D is a good example of the way that diet, when combined with genetic variation, can affect different people different ways.

Vitamin D actually refers to a group of five different fat-soluble secosteroids, the most important for our health being D₂ (also called ergocalciferol) and D₃ (or cholecalciferol).

Vitamin D is considered an essential vitamin; one that we need to get from our diet because we can’t make it for ourselves. It is interesting though, because, unlike the twelve other essential vitamins, humans do actually have the capacity to synthesise vitamin D3.

In fact, humans can synthesise vitamin D3 in greater quantities than we can normally obtain from our diet.

If we can make vitamin D ourselves, why do we classify it as an essential vitamin? Well, the catch is that we need sunlight to make vitamin D3. Specifically, we need UV-B to convert cholesterol into a precursor of vitamin D3 that can then be converted into actual vitamin D3.

What Happens If You Don’t Get Enough Vitamin D?

The human genome encodes all the proteins that our bodies need to grow, survive and reproduce. We don’t, however, need all these proteins all the time. What we need is for the right proteins to be turned on at the right time.

One of the ways the body achieves this is by using transcription factors.

Transcription factors are proteins that bind to sections of DNA, adjacent to genes, and either stop or promote the expression of the protein encoded by that gene.

Vitamin D is a crucial part our metabolism because it is essential for the operation of a transcription factor called vitamin D receptor (VDR).

Without vitamin D, VDR can’t start or stop the production of the proteins that it controls.

Without Vitamin D Bad Things Happen

The most well-known consequence of vitamin D deficiency is the childhood disease called rickets.

Children with rickets cannot make strong enough bones and as they grow, and gain weight, their bones start to bend causing limb deformities, delayed growth, muscle weakness, and dental problems.

In adult’s vitamin D deficiency can lead to soft bones (osteomalacia), osteoporosis, immune deficiency, muscle aches and chronic fatigue. In short, sufferers are more susceptible to disease, bone fractures and muscle weakness.

Vitamin D Deficiency is Surprisingly Common

Worldwide, it is estimated that more than one billion people are deficient in vitamin D. Usually this is because people don’t get exposed to sufficient sunlight.

The problem can be climatic, you live in England, for example, which is famous for rainy days and cloudy skies. But vitamin D deficiency is also common in areas such as the Middle-East, Asia, Africa and South America where there is normally loads of sunlight.

This can be partly explained by our lifestyle: we wear more clothing, we limit exposure to sunlight so we don’t get skin cancer, and sunlight can be blocked by air pollution.

Another important factor is that melanin in the upper layers of the epidermis can limit the amount of UV-B that can be used for vitamin D synthesis.

So, when combined with modern lifestyles, darker skinned people can be more vulnerable to vitamin D deficiencies.

Vitamin D and Human Evolution

The current situation is something of a reversal of what occurred over the course of our evolution.

Current theories suggest that dark skinned ancestors who moved into areas such as northern Europe were put under severe evolutionary pressure because the lack of sunlight in these climes favoured lighter skinned individuals who could synthesise sufficient vitamin D.

My Irish ancestry thus explains my pasty complexion and propensity to burn when exposed to minute amounts of sunlight.

Why Don’t We Add Vitamin D to Our Food

If vitamin D deficiency is such a problem, why don’t we just add it to our food, like we do with folic acid (vitamin B9), thiamin (B1) and vitamin A?

The answer is that we used to but stopped.

In the 1600s, during the early industrial revolution, rickets became a massive problem in the urban ghettos of northern Europe. Living in close set houses under the pall of pollution from industrial coal burning children weren’t getting enough sunlight.

By 1900 it was estimated that an amazing 80–90% of children living in Northern Europe and in the Northeastern United States had suffered from rickets.

Public Health Campaigns Eradicated Rickets, Eventually

Gradually science caught up, but it took a while. Around 200 years passed before we made a connection between sunlight and rickets. And it wasn’t until the early 1900s that we understood the role of vitamin D.

Public health campaigns encouraged parents to get their kids into the sun but it was also realised that if you can’t get vitamin D from sunlight then you need to get it from your diet.

So fortifying foods, particularly milk, with vitamin D became common. In fact, adding vitamin D to food became something of an obsession in the 1930s with all manner of foods getting the vitamin D treatment, including custard, hot dogs and even beer.

By the 1930’s the combination of public awareness of the importance of sunlight and the supplementation of many food stuffs with vitamin D led to the eradication of rickets.

Problems With Vitamin D Fortification

Even though rickets had been eradicated, there was a problem. In the 1950s, doctors started reported increases in infant hypercalcaemia.

Hypercalcaemia is an increase of calcium in the blood that can lead to over-calcification of bones and soft tissues including arteries, heart and kidneys. If left unchecked, it can culminate in kidney failure and eventually death.

One of the ways that you can develop hypercalcaemia is by ingesting, over time, large amounts of vitamin D.

Blaming vitamin D for these cases of infant hypercalcaemia, most governments started introducing regulations to limit the liklihood of toxicity. Only baby formula has mandatory vitamin D fortification rules in most countries.

The Pendulum Swings Back

Today though, given that vitamin D deficiency is again becoming an issue, many countries are actively debating whether to re-introduce the fortification of foods with vitamin D.

In the UK, for example, growing rates of vitamin D deficiency has prompted serious debate about supplementing food, especially dairy products, with vitamin D. One of the questions that health regulators wrestle with, though, is what is the optimal intake of vitamin D?

Part of the problem is that there is often an expectation that one size will fit all. That we can find a daily dosage of vitamin D appropriate to everyone in society. But this is unlikely to be the case.

Firstly, we now know that many of the hypercalcaemia cases in the 1950s were actually attributable to rare genetic conditions causing an extreme sensitivity to vitamin D. Not the result of an excessive consumption.

In recent years it has also become clear that sensitivity to vitamin D can vary significantly from one person to another. That is, individuals can be divided into low responders and high responders to vitamin D (here and here for studies).

It’s conceivable, if vitamin D supplementation is re-introduced, that a low responder would still get insufficient vitamin D from fortified food and a high responder would get too much.

So, how much vitamin D should be added to our food? It’s hard to say.

From a personal perspective, the trick here is to know how much vitamin D you need. Work out if you are a low or high responder. Then you can take appropriate steps to ensure you get sufficient vitamin D.

This is why things like genomic technology are so important. As our knowledge grows medicine can be personalised based on the genomic profile of the patient. Low responders get high doses and high responders get lower doses.

That’s a story for another post though.

Conclusion

Vitamin D is just one example of the problems that face health regulators when dealing with population level treatments. Other examples are not hard to find; vaccines used in a recent pandemic spring to mind.

The fact is that genetic variation can make it hard to know how a specific person will react to drugs and other types of medical intervention. Sometimes variations in the way different people react to a treatment will be discovered during trials, but sometimes they are not.

Because of this taking any medication is very serious thing. It should only be done on the advice and under the supervision of a professional.

This is the internet age though, so of course there are all sorts of unqualified people talking about which drugs or treatments you should take, and those you shouldn’t.

Often this advice is based on the personal experience of a single influencer. Now we know though, unless you happen to be a genetic clone of that influencer, your experience could be very, very different.