Case Study: Homocysteine, B12, and folate

Homocysteine is an amino acid that occurs in the body as an intermediate in the metabolism of methionine and cysteine. Folic acid is a vitamin of the B complex, found especially in leafy green vegetables, liver and kidney. (Both these definitions are from the New Oxford American Dictionary on my MacBook.) Folic acid is B9, and folate is a salt of folic acid, but the two names are used interchangeably.

Homocysteine is normally broken down and recycled so that it doesn’t accumulate. This relies on sufficient amounts of vitamins B12, B6 and B9 being available to facilitate this process. Homocysteine, abbreviated Hcy, is a highly inflammatory substance associated with much higher risks of cardiovascular events. Research (AHJ 2004) has shown that rHcy causes endothelial dysfunction and damage, accelerates thrombin formation, inhibits native thrombolysis, promotes lipid peroxidation through free radicle formation and induces vascular smooth muscle proliferation and monocyte chemotaxis. 

Naturally, we should strive to keep Hcy levels in our blood as low as possible. There is no healthy minimum for it. In other words, the lower the better. And conversely, the higher its concentration, the worse off you are in terms of the potential for damage to the arteries and cardiovascular events. For a detailed look at Hcy in relation to vascular disease, read this article by Dr Neville Wilson, (thanks Ivor Cummins).

Last week I explained something about Hcy, B12, and folate to my son who was getting ready to go back to university for his second year (studying Philosophy and Modern History at St-Andrews). Afterwards, I thought it would be useful to share this with you, and I started working on this post.

This story is drawn from my own personal history. It is a case study with me as the primary subject using data I have collected from regular blood tests over these last seven years. However, I also use data from both my mother’s and my son’s blood test results that happen to be critical for understanding my own blood test results. Below, I describe the whole story and analysis of the data in detail. If you are not interested in the details, the punchline is this:

If your homocysteine levels are high, you should supplement with B12 and fully active folate in order to ensure the body has what it needs to process it. Some people lack the enzyme needed to activate the folic acid we get from food. This prevents the body from breaking down homocysteine that consequently accumulates in the blood.  This is a genetically transmitted trait, which I think I have inherited and transmitted to my son. Because of it, we must supplement with activated folate to ensure breakdown of Hcy.

 

The first time I read about Hcy was many years in Anthony Colpo’s book The Great Cholesterol ConThe subject was discussed towards the end of the book in a short chapter, but I was left with a strong impression. Colpo emphasized that Hcy—unlike cholesterol—was a good predictor for heart disease. And it wasn’t just good: it was one of the best. But this wasn’t the only reason it made such an impression on me.

I read Colpo’s book after reading Uffe Ranvnskov’s Fat and Cholesterol are Good for You, and Malcom Kendrik’s The Great Cholesterol Con, both of which were about fat, cholesterol and heart disease, but neither of which discussed homocysteine. Then I read Gary Taubes’s Good Calories, Bad Calories, and again, Hcy wasn’t given the share of attention it seemed to deserve based on Colpo’s comments. If you’re new here, or if you need a refresher, you should read But what about cholesterol and At the heart of heart disease.

The first time I got my Hcy levels checked was on August 27 in 2012. The result was 18.3 micromol per litre. On the results, the reference range was 5 to 15; moderately elevated was 15 to 30; and elevated was indicated as anything greater than 30 micromol per litre. Beside the middle range, it was written vitamin deficiency in parentheses. But it wasn’t written what vitamin deficiency would cause elevated Hcy. The doctor from whom I had requested the test didn’t know either. (As you might have experienced for yourself, most MDs don’t really know much when it comes to blood test results.)

 

I had already started supplementing with B12 by that time. Most of us, as vegetarians, quickly and usually angrily dismiss nutritional advice or warnings of potential problems from deficiencies that non-vegetarians love to offer when they find out we don’t eat meat. We usually interpret these as justifications of their feelings of guilt for not being vegetarians themselves. At least I know I did when I was vegetarian. Although most people who do give their unsolicited advice are rarely knowledgeable in the subject matter, I now know that I was dead wrong about my quick dismissal of several things in relation to dangerous deficiencies that come about when we eliminate meat and animal products from our diet. Vitamin B12 is surely the best example.

It was after reading this article on B12 by Mercola that I came to realize how disastrous were the consequences of living with low levels of B12, and in my case, how disastrous were the consequences of having been vegetarian for 20 years. I started supplementing right away, and got my first B12 blood test a few months later in 2010 on September 8. The result was 271 pg/ml. According to the lab who did the test, this was within range. But I knew it wasn’t. I knew this was much too low, and that I desperately needed to correct this as fast as possible, stop and hopefully reverse the neurological degradation associated with my long-standing B12 deficiency.

In that article was also underlined the connection between low B12 and high Hcy levels. It read: Cardiovascular and cerebrovascular diseases have a common risk factor – increased homocysteine levels in blood. Studies show insufficient amounts of folic acid and vitamin B12 can elevate your homocysteine levels, potentially increasing your risk for heart disease and stroke. So, of course I was worried. I was also angry at myself for having been so stupid and stubborn all these years… these 20 long years. But at least I now knew what I had to do: I needed to boost B12 levels and keep them high.

And I did. Look at how my B12 levels evolved over 7 years:

ts_b12

Blood B12 levels measured over seven years since September 2010.

 

Does seeing this make you wonder how the Hcy levels evolved? My expectation was that Hcy would drop as B12 rose. With some time delay of course, but still: as B12 levels increased, homocysteine concentration would decrease. Here is what happened:

ts_hcy

Blood homocysteine levels measured over five years since August 2012.

Not so obvious to interpret, right?

Let’s look at all the tests in which both B12 and Hcy were measured, and plot them one against the other. It’s called a correlation plot, and this is what we find:

hcy_vs_b12

Homocysteine plotted against B12. Data point numbe labels show chronological order of tests.

So, there clearly is an inverse relationship between levels of Hcy and B12. There is no doubt in this. But at least for me, it’s not very tight. The correlation coefficient and the uncertainty on it quantify this relationship.

The coefficient can have any value between -1.0 and 1.0: a value of 1.0 signifies perfect correlation; a value of -1.0 signified perfect anti-correlation; and a value of 0 signifies that there is no correlation at all. The uncertainty on the coefficient quantifies how well the coefficient is determined from the data points, and therefore how loosely or tightly they are spread around the overall trend in the data set.

A coefficient of -0.66, as we found, tells us that there is indeed an anti-correlation in the relationship between Hcy and B12 concentrations. The uncertainty of 0.22 tells us that the correlation is not so tight. And when we look at two time series above, we see that although B12  has been above 600 pg/ml since 2014, Hcy levels remained more or less flat until the end of 2016.

My initial interpretation was that because I had been B12 deficient for basically 20 years, correcting that long-standing deficiency, and repairing the damage caused by it to the body and in particular to the nervous system, required maintaining consistently high levels of B12 for a long time, allowing the body the time needed to repair itself: two decades of B12 deficiency could obviously not be corrected in a few months. Maybe it was only after these 7 years of intensive B12 supplementation that the positive results were beginning to manifest themselves in this way.

And by intensive, I mean pretty serious. I started taking oral supplements of 2000 mcg per day; then transitioned to patches which are more effective because the B12 is absorbed directly through the skin without having to go through the digestive system; and finally moved on in early 2015 to monthly intramuscular injections of 5000 mcg of methycobalamin. Nevertheless, Hcy remained pretty much the same, even after months of injections. What was going on? Why wasn’t Hcy dropping?

 

Maybe you are thinking that there might be another way we could use to check how much influence B12 levels have on Hcy? Well, I have something I think is quite remarkable to share with you.

At the very end of July 2014, I brought my mother to a specialized blood analysis clinic, and ordered the complete set of tests listed on my essential blood test reference sheet. The results came back a few days later: her B12 was at 292 pg/ml; her folic acid was at 11.6 ng/ml; and her Hcy was at 30.5 micromol/l. She was 82 and, just for the record, it was the first time in her life that her B12 and Hcy levels had been measured in a blood test.

I immediately got a friend of hers and ex-nurse to give her methylcobalamin injections a couple of times a week. Five weeks later in early September we repeated the test for homocysteine. The result was 9.5!

My 82 year old mother’s homocysteine levels went from 30.5 to 9.5 micromol/l in 5 weeks following 10 injections of 1 mg doses of methylcobalamin B12.

She was out of the red. At least on that front. Hcy of 9.5 micromol/l is still moderately elevated when we consider that we would ideally have none. But 30.5 was dangerously high. This, to my mind, is strongly indicative of the crucial importance and immediate effect of vitamin B12 on homocysteine metabolism.

It wasn’t a tightly controlled experiment where everything was kept the same except the one variable under investigation, which in this case would have been the B12 injections. It wasn’t, because my mother did also at the same time adopt a new dietary regimen, following an alkalizing, very low carb, low protein, high fat, intermittent fasting cleansing protocol I had designed for her, that also included quite a number of other supplements. All were food supplements: vitamins A-D-K2, niacinamide, co-enzyme Q10 as ubiquinol, phospholipids as sunflower lecithin, omega-3s as krill oil, turmeric extract, tulsi extract, chlorella and spirulina, magnesium, zinc, iodine, etc.

Certainly it is true that everything influences everything else, but there’s no question in my mind that as far as homocysteine was concerned, the most important element in this protocol was the intramuscular injection of methylcobalamin approximately every three days. There is also no question that achieving such a drop in Hcy levels at such an advanced age and in so little time is nothing short of amazing.

The point of my retelling of this was to present direct evidence of the strength of the relationship between B12 levels and Hcy concentration. I think it does. Obviously, you are to draw your own conclusions.

 

Coming back to my case, in the fall of 2013 I stumbled upon The Complete Blood Test Blueprint in which Joseph Williams, a knowledgeable, experienced, and kind MD, was interviewed by Kevin Gianni, the host of Renegade Health, in a series of interviews that covered a large number of blood tests in great detail. I learned a lot things listening to Dr Williams. Admittedly, I was disappointed by the lipid panel discussion, and in particular by the discussion of cholesterol and lipoproteins. But putting this aside, I was generally very impressed.

Dr Williams talked about B12 deficiency at length, but I was already well versed in the subject by that time. I had recently read the book Could it be B12?, made detailed notes of it, and then posted for you B12: your life depends on it. Dr Williams also talked about Hcy. In that discussion was mention of the fact that in addition to B12 (cobalamin), B6 (pyridoxine) and particularly B9 (folic acid) were also essential for breaking down Hcy. I didn’t really think much of it, simply because my diet was and always had been rich in leafy greens, which naturally ensured a high intake of folic acid.

A few years and several blood tests later, I listened to the interviews again. And this time, something caught my attention in the part on homocysteine that hadn’t the first time: it was mentioned, in passing towards the end of the discussion, that some genetically predisposed people lacked the enzymes needed to activate folic acid; and that these people therefore needed to supplement with the already active form of B9 called tetrahydrofolic acid.

It caught my attention because by that time I had several measurements of Hcy that, even with my continued and even intensified B12 supplementation, were not showing evidence of going down. Remember: I started injections in early 2015. But there was something else that made this comment stand out for me: my son’s recent blood test results.

 

In July 2016 I brought my son to get a complete blood test that comprised all the markers I usually test for, together with all the major hormones, in order to have a baseline for him in his prime. It is certainly true that we can talk about optimal levels for each of the hormones we know and can test for. But our own personal ideal hormonal profile is unique to us. And the best time to get a baseline is when we are 18 years old: full grown adults at our youngest.

Laurent’s B12 was 578 pg/ml, his folic acid was 23 ng/ml, and his Hcy was 10.9 micromol/l. At 18, having had no major health issues, no accidents or serious diseases, a remarkably healthful fresh, green, organic, low carb, high fat diet of unprocessed whole foods for most of his life, I thought that this slightly elevated Hcy could be due to one of three things: either his body was still B12 deficient and just slowly building up its B12 stores, even though the three of us had all started with supplementation and patches at the same time; he was one of these people Dr Williams had made reference to who lacked the enzyme to activate folate, and therefore couldn’t effectively break down Hcy; or both.

I immediately ordered activated folate for us, and we started taking it in August 2016. If you take a look at the second plot that shows my Hcy levels as a function of time, you can see that it was just around 18 micromol/l at the end of July. And half a year later, towards the end of 2016, my Hcy level was the lowest it had ever been. Obviously, I was very happy to see this major improvement in achieving a drop in Hcy, something I had been trying to do for so many years. Therefore, also obviously, I continued taking activated folate. As you can see from the next two data points in 2017, Hcy was measured at 10 and then 8 micromol/l. We haven’t made another blood test to check Laurent’s levels. We’ll do that around Christmas at the end of this year when he comes back for the holidays.

Can we see how strong the relation between folate and Hcy actually is? We can plot the measurements we have one against the other like we did above for B12 and Hcy. What we find is this:

hcy_vs_folate

Homocysteine plotted against folate. Data point number labels show chronological order of tests. Arrows mark upper limits.

The relationship is very clear and linear. But I have to admit that I have cheated your eye a little bit. The measurements of folic acid are capped at 24: any value above that is simply reported as greater than 24. This was the case in tests (4), (8), (9), and (10). I show this with little arrows pointing towards higher values. Because the last three measurements were so close together in time, for the sake of clarity in the plot, I placed them at 25, 26 and 27, inversely proportional to the Hcy level. This is why they appear to follow the line. Otherwise, they would be at on the left edge of the arrows, one on top of the other, aligned with point (4), all at 24 on the x-axis. Note that I also plotted my son’s results (labelled as such), adding a data point at (23, 11).

 

What can we conclude from this investigation? Well, it isn’t totally clear cut and straight forward. I admit. But let’s review the facts:

For me:

  • I was 38 years old at the time of my first B12 test.
  • My B12 levels were low for 20 years: 270 pg/ml when first tested after few months of supplementation.
  • My Hcy levels were high at 18 micromol/l about two years after starting B12 supplementation.
  • B12 is necessary to break down Hcy.
  • It took me 3 years of oral and patch B12 supplementation to reach 600 pg/ml.
  • In early 2015 I started monthly B12 injections.
  • Only after almost 2 years of injections did my Hcy levels drop below 10 micromol/l.
  • But this precipitous drop in Hcy was concurrent with the start of supplementation with activated folate.

For my mother:

  • She was 82 years old at the time of her first B12 test.
  • Her Hcy levels were very high at 30 micromol/l.
  • Her B12 levels were low for who knows how long: 292 pg/ml when first tested.
  • She received approximately 10 injections of 1 mg in five weeks.
  • Her homocysteine levels dropped from 30 to 9.5 micromol/l.

For my son:

  • He was 18 years old at the time of his first B12 test.
  • His homocysteine levels were moderately high at 11 micromol/l.
  • His B12 levels were 578 pg/ml.

In addition to this, we have the plots above that show inverse relationships both between Hcy and B12, and between Hcy and folic acid. From this, there are at least three very clear conclusions we can draw:

  1. Low levels of B12 are associated with high levels of homocysteine,
  2. Higher levels of b12 are associated with lower levels of homocysteine, and
  3. Raising B12 levels leads to a decrease in homocysteine concentration.

At this stage and with the data we currently have, going further is more speculative. But here is what I think:

  1. I am one of these people that lacks the enzymes to activate folic acid.
  2. I might have inherited this trait from my mother or from my dad (considering how well she responded to intensive B12 therapy), and it was probably transmitted to my son.
  3. I was B12 deficient, and correcting this deficiency didn’t lower my Hcy levels.
  4. It was only when I started taking activated folate supplements that Hcy levels dropped quickly and significantly.

The reason I think this comes from two lines of reasoning. The first is that, as I just mentioned, it is only when I started taking activated folate that my Hcy levels dropped below 10 for the first time in seven years since the start of B12 supplementation.

The second is that even though both my mother and I were definitely B12 deficient, both probably for a long time, and that this would necessarily have led to an accumulation of Hcy in the blood that would have been greater in her case than in mine due to her age; my son was only 18 years old, and could not have been B12 deficient, at least not for almost 10 years. Nevertheless his Hcy levels were moderately elevated.

This is what I told him the other day. It took me only 5 minutes to tell him; it has taken me a lot longer to write this post. But I think the details are important if we are to understand things well. And by this I mean know what we understand, and know what we do not understand; know what conclusions we can make, and know what is hypothesis or speculation.

It’s not possible to be sure at this stage. We need more data and more experiments. But it’s not easy to gather such data, just because it takes a long time and strong commitments to be consistent with a supplementation programme over months and often years. If you have similar data and are willing to share, I would be happy to take a look at them.

Data like these trace and reveal so much about what’s happening inside our body, below the skin, far deeper than our eyes can see. But we can only begin to understand these measurements and the processes that drive their evolution by spending the time to look at them in detail. This is what we did here together. I hope you found it interesting.

Do you know what are your blood levels of homocysteine, B12, and folate? If not, you better get that checked out.

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The sun, our Earth, and the colour of your skin

Skin colour is the most obviously visible manifestation and expression of our evolutionary history. This history is carried over the course of hundreds of thousands of generations and tens of thousands of years. What we have to understand is that each one of us—as an individual, a person, a self—has nothing to do with the colour of our skin, the colour of our skin has nothing to do with us, and we have no choice in the matter. What we must also understand is that to be optimally healthy, we have to live and eat in accordance with the colour of our skin and what information it carries about our ancestry. All of this is true for you, and it is true for everyone of every colour in the magnificent spectrum of human skin colours as it exists on the planet today. Let me explain why.

skinColourPalette

(Photo credit: Pierre David as published in this article of the Guardian)

The Sun, like every other star in the universe, formed from the gravitational collapse of a huge cloud of gas. This happened about 5 billion years ago. All the planets, like every other planet everywhere in the universe, formed from the left over debris that wasn’t needed or used in making the Sun, and that remained orbiting around it in a large, flat accretion disk consisting of 99% hydrogen and helium gas and only 1% of solid dust particles. In a blink of an eye, a million years or so, the disk was replaced by a large number of planetesimals. An additional couple hundred million years or so, and the planets of our Solar system were formed.

Beyond the snow line, the radius from the Sun past which water can only exist as ice and where the temperature is below -120 C, volatiles froze into crystals, and were formed from massive icy cores the gas giants: Jupiter (the king at 320 times the mass of the Earth), Saturn, Uranus and Neptune. Within the snow line were formed the rocky planets: Mercury, Venus, Earth and Mars. About 4.5 billion years ago the Solar system was in place. It was in place but not quite like we know it today. It was fundamentally different in several ways, especially in regards to what concerns us here, which is how the Earth was: a fast-spinning burning inferno of molten rock spewing out of volcanos everywhere and flowing all over the globe, completely devoid of water, oxygen, carbon and other volatiles species.

The Earth formed more or less simultaneously with a very close neighbour about the size of Mars. Inevitably, soon after their formation, they collided. This apocalyptic encounter tilted the Earth off its original axis and destroyed the smaller planet that, in the collision, dumped its iron core into the Earth, and expelled about a third of our planet into the atmosphere. Most of the stuff rained back down, but some of the material lumped into larger and larger lumps that eventually resulted in the moon, our moon. When it formed, the moon was a lot closer—it would have looked twice as large as it does now, and the Earth was spinning approximately five times faster than it does today—a day back then would have lasted only 5 hours. Because of the proximity between them, huge tidal forces would have deformed the liquid Earth on a continuous cycle driven by its super short 5-hour days. This would have heated the Earth tremendously by squeezing its insides from one side and then from the other, and caused massive volcanic activity all over the globe.

But this inelastic gravitational interaction, this drag of the moon on the Earth worked, as it still does, to sap rotational energy from the Earth and transfer it to the smaller and far less rotationally energetic moon. This made, and continues to make, the Earth slow down, the moon speed up and therefore drift out into a progressively larger orbit. The moon’s drag on the Earth continues to make the Earth’s spin slower and the moon’s orbit larger, but at an increasingly slower rate, now of 3.8 cm per year. This will continue until there is no more rotational energy to be transferred from the Earth to the moon, at which point we will be tidally locked in order with the moon, and not only will we always see the same side of the moon as we do today, but the moon will also always see the same side of the Earth. For what it’s worth, this will happen way after the Sun has come to the end of its life, and thus in more than 5 billion years. So, for now, this is definitely not a major issue.

Besides this important difference in the Earth’s spin rate and its relationship with the moon, there were a lot of left overs from the Sun’s formation that had clumped up in asteroids and comets whirling around in all sorts of both regular and irregular orbits that had them sweeping across the Solar system from the furthest reaches and most distant places to the inner regions near the Sun and rocky planets. The Heavy Bombardment lasted for a period of approximately 500 million years from about 4.3 to 3.8 billion years ago. During this tumultuous early history of our Solar system, a lot of these asteroids and comets flying past the Earth and the other rocky inner planets were gravitationally captured and pulled in towards the planet to crash on the surface or just swoop down into the atmosphere, leaving behind all or some of their mostly volatile constituents: water and carbon compounds. The Earth would have been regularly bombarded by massive asteroids, and the energy dumped by the impacts would have made it a hellish place covered in flowing lava, obviously without any crust, but rather only molten rock flowing everywhere and volcanos spewing out noxious gases and spilling out more molten rock that merged into the already flowing streams of lava. Very inhospitable.

But with these brutal hundreds of millions of years of bombardment from asteroids and comets, water and carbon compounds were brought to our planet. Given how hot it was, the water was in the atmosphere as vapour, and so were the carbon monoxide and dioxide as well as methane. However, these were now bound to the planet gravitationally and couldn’t escape back into space. Once the bulk of the randomly orbiting solar system debris had been cleared out and incorporated into the various planets onto which they had fallen, the bombardment came to an end, and the Earth started cooling down. It is believed that the last major sterilising impact would have hit the Earth around 3.9 billion years ago.

Cooling during a few thousand years allowed the formation of a thin crust. Further cooling then brought on thousands of years of rain that dumped most of the water vapour from the atmosphere onto the surface. This formed vast planet-spanning oceans. The whole planet was at this point still super hot, but also super wet, and therefore super humid, with the surface practically entirely underwater, lots of active volcanos all over the place but otherwise no mountains. Nevertheless, there would have been some  slightly more elevated places, like on the flanks of volcanos, that would have been dry at least some of the time, leaving some spots where water could accumulate in ponds and stagnate. As soon as these conditions were present, around 3.8 billion years ago, the Earth saw its first microbial life emerge.

Claims for the earliest evidence of life at 3.8, 3.7 or 3.5 billion years are still controversial, but it is well established that hydrogen cyanide dissolved in water produces a diversity of essential biological molecules like urea, amino acids and nucleic acid bases; that formaldehyde in slightly alkaline water polymerises to form a range of different sugars; that amino acids, sugars and nucleic acid bases as well as fatty acids have been found in carbonaceous meteorites; and that by 3 billion years ago, prokaryotes (organisms made of cells without a nucleus) were widespread.

There was a major problem, a major impediment to life, that had to be overcome. This was the fact that the entire surface of the Earth was exposed during the day to the Sun’s UV radiation, and UV rays destroy biological structures and DNA. The cleverest of tricks would have been to find a way to absorb these energetic photons and use the energy for something.

Nature is very clever: by 3.5 billion years ago, chlorophylls believed to have developed in order to protect proteins and DNA of early cells appeared, and chlorophyll-containing cyanobacteria—the oldest living organisms and only prokaryotes that can do this—had developed the ability to absorb light, use that energy to split water molecules and use the free electron from the hydrogen atom to sustain their metabolism, spewing out the oxygen in the process. Oxygen accumulated in the crust for a billion years before the latter became saturated with it and unable to absorb any more. Evidence for increasing oxygen levels in the atmosphere is first seen at around 2.5 billion years ago. By 2.2 billion years ago, oxygen concentrations had risen to 1% of what they are today.

Increasing concentrations of reactive and corrosive oxygen was devastating for all forms of life that, at this stage, were all anaerobic: the oxygen was combining with everything it got in contact with creating all sorts of reactive oxygen species (free radicals) that went around causing damage, exactly as they do in our bodies and that of all animals today, and which, in the absence of antioxidants to neutralise them accelerated ageing and death. These were the only card that these simple anaerobic organisms were dealt.

Nevertheless, for another reason entirely, atmospheric oxygen was a blessing because it turned out to be an excellent UV shield. Not only that, but the splitting of oxygen molecules (O2) into oxygen atoms promoted the recombination of these free-floating oxygens into ozone (O3) that turns out to be an even better UV absorbing shield. So, the more photosynthesis was taking place on the surface, the greater the concentration of atmospheric oxygen grew. The more molecular oxygen there was in the atmosphere, the more ozone could be formed. And the more ozone there was to protect and shield the surface from the harsh UV radiation from the Sun, the more complex and delicate structures could develop and grow. Pretty cool for a coincidence, wouldn’t you say?

By 2 billion years ago—within 200 million years—the first eukaryotes appear (organisms made of cells with a nucleus). This makes good sense considering that these simple organisms and independently-living organelles had a great survival advantage by getting together in groups to benefit from one another and protect each other behind a membrane while making sure the precious DNA needed for replication and proliferation was well sheltered inside a resilient nucleus. Note here that these would have been trying to protect themselves both from the damaging UV radiation streaming down from the Sun (it’s estimated that DNA damage from UV exposure would have been about 40 times greater than it is today), as well as from the corrosive oxygen floating in the air (imagine how much more oxidising it is today with concentrations 100 times greater than they were). And in there, within each of these cells, there were chloroplasts—direct descendants from the first UV absorbers and converters, the cyanobacteria—whose job was to convert the photons from the sun into useful energy for the cell.

In all likelihood unrelated to this biological and chemical evolution of the Earth’s biosphere and atmosphere, a long period of glaciation between 750 and 600 million years transformed the planet into an icy snow and slush ball. And with basically all water on the surface of the globe having frozen over, all organisms under a thick layer of ice and snow, photosynthetic activity must have practically or completely ceased. Fortunately, without liquid water in which to dissolve the atmospheric carbon dioxide into the carbonic acid that in turn dissolves the silicates in the rocks over which is streams and carries down to the ocean floor for recycling by the active tectonic plates, all the carbon dioxide sent into the atmosphere by the volcanos just accumulated. It is believed to have reached a level 350 times higher than it is now. This is what saved the planet from runaway glaciation.

Thanks to this powerful greenhouse of CO2, the ice and snow eventually melted back into running streams and rivers, and flowing wave-crested seas and oceans. With water everywhere and incredibly high concentrations of CO2, plant life exploded. And soon after that, some 540 million years ago, complex animals of all kinds—molluscs, arthropods and chordates—also burst into existence in an incredible variety of different body plans (morphological architectures), and specialised appendages and functions. This bursting into life of so many different kinds of complex animals, all of them in the now already salty primordial oceans, is called the Cambrian Explosion. Complex plant life colonised the land by about 500 million years ago, and vertebrate animals crawled out of the sea to set foot on solid ground around 380 million years ago.

Clearly, all plant life descends from cyanobacteria, first to develop the ability to absorb UV radiation, and without complex plant life, it is hard to conceive of a scenario for the evolution of animal life. The key point in this fascinating story of evolution of the solar system, of our Earth and of life on this planet as it pertains to what we are coming to, is that the light and energy coming from the Sun are essential for life while being at the same time dangerous for the countless living organisms that so vitally depend on it. In humans and higher animals this duality is most plainly and clearly exemplified by the relationship between two essential micronutrients without which no animal can develop, survive and procreate. These vital micronutrients are folate and vitamin D.

What makes folate (folic acid or vitamin B9) and vitamin D (cholecalciferol) so important is that they are necessary for proper embryonic development of the skeleton (vitamin D), and for the spine and neural tube as well as for the production of spermatozoa in males (folate). Vitamin D transports calcium into the blood from the intestinal tract making it available to be used in building bones and teeth; folate plays a key role in forming and transcribing DNA in the nucleus of cells, making it crucially important in the development of all embryonic cells and quickly replicating or multiplying cells (like spermatozoa).

Here’s the catch: vitamin D is produced on the surface of the skin (or fur) through the photochemical interaction of the sun’s UV-B rays and the cholesterol in the skin; folate is found in foods, mostly leafy greens (the word comes from the latin folium that means leaf), but it is broken down by sunlight.

What this translates to is this: too little Sun exposure of the skin leads to vitamin D deficiency, which leads to a deficiency in the available and useable calcium needed to build bones, which in turn leads to a weak, fragile and sometimes malformed skeletal structure—rickets; too much Sun exposure leads to excessive breakdown of folate, which leads to folate deficiency, and which in turn leads to improper development of the quickly replicating embryonic cells of the nervous system and consequent malformation of the neural tube—spina bifida.

The most important thing of all for the survival of a species, is the making and growing of healthy babies and children so that they can make and grow other generations of healthy babies and children. This is true for all living beings, but it is not just true: it is of the highest importance, and it has been—taking evolutionary precedence over everything else—since the dawn of life on Earth. Here is how the biochemistry of the delicate balance between these two essential micronutrients evolved.

Six to seven million years ago, our oldest ape-like ancestors walked out of the forest and into the grassy savannah most probably to look for food. (Isn’t this what also gets you off the couch and into the kitchen?). It is most probably the shift in climate towards hotter and dryer weather and, in response to that, the shrinking of their woodlands, that pushed them to expand their foraging perimeter out into the plains that were growing as the forests were shrinking.

Our first australopith ancestors, these ancestors that we share with modern chimpanzees, would have been in all likelihood covered in hair with pale skin underneath (just as chimps are today), their exposed skin growing darker in time with exposure to sunlight. Having left the forest cover, they were now exposed to the hot scorching Sun most of the day, while walking around looking for food, before going back to the forest’s edges to sleep in the trees.

Natural selection would now favour the development of ways to stay cool and not overheat. This meant more sweat glands to increase cooling by evaporation of water on the surface of the skin. It also meant less hair for the cooling contact of the air with the wet skin to be as effective and efficient as possible. But less hair implied that the skin was now directly exposed to sunlight. To protect itself from burns and DNA damage, but also to protect folate, natural selection pushed towards darker skin: more melanocytes producing more melanin to absorb more photons and avoid burning and DNA damage.

In these circumstances, the problem was never too little sun exposure; it was too much exposure, and thus sunburns and folate deficiency. So these early hominids gradually—and by gradually is meant over tens of thousands of years—became less hairy and darker-skinned. They also became taller and leaner, with narrow hips and long thin limbs: this gave less surface area exposed to the overhead sun but more skin surface area for sweating and cooling down, together with better mechanical efficiency in walking and running across what would appear to us very long distances in the tens of kilometres every day, day after day, in foraging and hunting, always under a blazingly hot sunshine. This process that is described here in a few sentences took place over millions of years, at least 3 or 4 and most probably 5 or 6 million years. The Turkana boy, a 1.6 million years old fossilised skeleton is definitive proof that by that time, hominids were already narrow-hipped and relatively tall.

From an evolutionary standpoint it couldn’t be any other way. While keeping in mind that we are still talking about ancient human ancestors, and not modern homo sapiens, nonetheless, did you, as you were reading these sentences, start to wonder who today would fit such a physical description of being hairless, dark-skinned, tall, lean and narrow hipped? Naturally: savannah dwelling modern hunter-gatherers, and, of course, the world’s best marathon runners. It makes perfect sense, doesn’t it?

Taking all currently available archaeological, paleontological, anthropological, as well as molecular and other scientific evidence as a coherent whole brings us to the most plausible scenario in which all humans on the planet today descend from a single mother who was part of a community of people living somewhere on the western coast of Africa; that it is this group of modern homo sapiens that first developed and used symbolic language to communicate and transmit information and knowledge acquired through their personal and collective experiences; and that it was descendants of these moderns who migrated in small groups, in a number of waves, first into Asia and later into Europe, starting 70 to 100 thousand years ago.

It is very interesting that we also have evidence that moderns had settled areas of the middle east in today’s Israel and Palestine region as early as 200 thousand years ago, and that these moderns shared the land and cohabited with Neanderthals for at least 100 thousand years, using the same rudimentary tools and technologies, without apparently attempting to improve upon the tools they had. Meanwhile, this other group of western African coast moderns had far more sophisticated tools that combined different materials (stone, wood, bone), as well as decorative ornaments and figurines.

Thus, although equal or close to equal in physical structure, appearance, dexterity and skills—a deduction based on fossils and evidence that newer and better tools were immediately adopted and replicated in manufacture by moderns to whom they were introduced by other moderns—it is clear that different and geographically isolated communities of moderns ate differently, lived differently, developed differently and at different rates.

This is not surprising, really. Some children start to speak before they turn one, while other do not until they are two, two and a half or even three. Some children start to walk at 10 or 11 months, while others just crawl on the ground or even drag their bum in a kind of seated-crawl until they are three or more. And this is for children that watch everyone around them walking all day long, and listen to everyone around them speak using complex language also all day long. Now, what do you think would happen if a child grew up without being exposed to speech? Why would they ever, how could they ever start to speak on their own, and to whom would they speak if nobody spoke to them?

Fossil evidence shows that the structures in the ear and throat required for us to be able to make the sounds needed for refined speech and verbal communications were in place (at the very least 200 thousand years ago) tens and even hundreds of thousands of years before the first evidence of symbolic thought (70-50 thousand years ago) and together with it, it is assumed, advanced language.

Symbolic thinking in abstract notions and concepts is the most unique feature of our species. It is the hallmark of humans. And it is the most useful and powerful asset we have in the evolutionary race for survival. Sophistication in symbolic thought can only come with sophistication in language and in the aptitude for language: it is only by developing and acquiring more complex language skills that more complex symbolic thinking can come about, and more sophisticated symbolic thinking naturally leads to developing a more sophisticated and refined language in order to have the means to express it.

It’s surely essential to recognise that this is as true for our ancestors, those that developed that first symbolic language, as it is for you and me today. The difference is that then, the distinction was between those few moderns that used symbolic language and those that didn’t, whereas today, the distinction is more subtle because everyone speaks at least one language to a greater or lesser extent. Nonetheless, anyone can immediately grasp what is described here by listening to Noam Chomsky lecture or even just answer simple questions in the course of an interview.

As they moved northward, settling in different places along the way, staying for thousand or tens of thousands of years, then leaving their settlements behind, either collectively or in smaller groups, and moving on to higher latitudes before settling again somewhere else, these people encountered a wide range of different climates and geographical conditions: usually colder, sometimes dry and sometimes wet, sometimes forested and sometimes open-skyed, sometimes mountainous and sometimes flat. In all cases, they were forced to immediately adapt their living conditions, building suitable dwellings and making adequate clothing. This, we know for sure, because they would have simply not survived otherwise, and it is only those that did survive that are our direct ancestors.

Evolutionary adaptation through natural selection of traits and characteristics arising from small—and, on their own, insignificant and typically unnoticeable—random genetic mutations also took place as it does in every microsecond and in every species of animals and plants. But this, we know to be a slow process that is measured on the timescale of tens of thousands of years (10, 50 even 100). Now, consider the evolutionary pressure—the ultimate evolutionary pressure—of giving birth to healthy and resilient offspring that will grow up to learn from, take care of, and help their parents. The most pressing evolutionary need at these higher latitudes was for the body to more efficiently make and store vitamin D from the incoming UV-B rays that, (and this is an important detail often overlooked or under appreciated), make it to the surface only when the Sun is high in the sky and have less atmosphere to go through. This stringent restriction on the few hours near midday when UV-B can make it to the surface is both constraining and life-saving: it is constraining because only during those hours can the essential vitamin D be made, and it is life-saving because a continual exposure to this energetic, DNA-damaging UV radiation would in time sterilise the surface of the entire planet.

The higher the latitude, the lower the Sun’s path on the sky throughout the year and especially during the winter months. Therefore, the shorter is the season during which UV-B rays reach the surface and during which it is possible for vitamin D to be produced on the skin or fur of animals. The only solution to this severe evolutionary pressure is as little body hair and as little pigmentation as possible (think of the completely white polar bears, arctic wolves, foxes and rabbits). As an aside, what else do you think as advantageous in the cold? The opposite as what is in the hot sun: more volume for less surface area; a smaller and stockier build that keeps heat better, exactly as we see in the cold-adapted Neanderthal.

Settled in a place that provides what we need to live relatively comfortably, we tend to stay there. This has always been true, and even if it has changed in the last few generations in industrialised western countries, we have witnessed this phenomenon up until very recently on islands like Sardinia, Crete, or Okinawa, remote valleys in the Swiss Alps, the Karakoram, Himalayas or Andes, and in other geographically isolated pockets of people with genetic characteristics homogenous amongst themselves but distinct with respect to other human populations. And thus across the world we find a whole spectrum—a rainbow—of different colours and shades of skin, different colours of hair and eyes, different amounts and textures of body hair, of different physical builds and morphologies, of different metabolic and biochemical sensitivities, all seen on a continuum, all dependent upon the evolutionary history of the subpopulation where particular characteristics are seen to be present or absent to a greater or lesser extent, and all of this driven by the evolutionary pressures to adapt and maximise the survival probability of our offspring, our family, our clan, our species, by optimising the amount of folate and vitamin D through the delicate balance between not enough of the latter from under-exposure to UV-B’s that produce it, and not enough of the former from excessive exposure to the same UV-B’s that destroy it.

What this tells us is that, for one thing, we have absolutely nothing to do with the colour of our skin, eyes and hair, and nothing to do with any of the physical and biochemical characteristics we have inherited. It tells us that this has nothing to do with our parents or grand parents either, really, because these are particularities that have evolved over tens of thousands of years of evolution in a very long line of ancestors that settled in a place, stayed put and lived at a particular latitude in a particular geographical setting with a particular climate. It tells us, in the most obvious manner, that because this is so, discrimination based on colour or physical features is not jut unfounded, but it is simply absurd.

If you’re black, you’re black. If you’re white, you’re white. If you’re chocolate or olive-skinned, then you’re chocolate or olive-skinned. If you are “yellow” or “red” then that’s just how it is. And who cares how you phrase it or not, try to be “political correct” and avoid speaking of it. That’s just silly. All of it is simply just the way it is. In the same way, if you’re short or tall, hairy or not, thin or stocky, it is just the way it is. However you are and whatever features you consider, there is never anything more or less about it, never anything more or less about any of these features: it is an expression of our genetic ancestry going back not just a few but hundreds of thousands of generations.

What this also tells us is that we have to take this information into account in everything we do, especially in regards to what we eat, where we live, and how much or how little we expose ourselves to the Sun’s vitally important UV-B rays. Disregard for these fundamentally important details leads to what we see in the world in this modern era where we all live wherever we want, more or less, and find ourselves with our olive or dark brown skin living in at high northern latitudes, or with our fair or milk-white skin living near the equator with strong overhead sun all year round, and see the consequent high rates of vitamin D deficiency and rickets in our dark-skinned northern dwellers, together with the similarly high rates of folate deficiency and spina bifida in our fair-skinned southern dwellers.

In general, if you are dark-skinned you need to expose your skin to the sun a lot more than if you are fair-skinned, because you will both produce less vitamin D and store less. If you are fair-skinned you need less exposure and will tend to store the vitamin D more efficiently for longer periods of time. As for folate, we all need to eat (or drink) leafy greens (i.e., foliage) and green veggies.

However, there is an additional complication that makes matters worse (far worse) That complication is that in this day and age, we all live inside, typically sitting all day facing a computer screen, and sitting all evening eating supper and then watching TV. Not everyone, of course… but most people. Not only that, but most of us all over the world now eat more or less the same things: highly processed packaged foods usually high in processed carbs and low in good, unprocessed fats, high in chemicals of all kinds and low in nutrients, and hardly any leafy and green veggies or nuts and seeds. And boy do we love our Coke, our daily bread, our fries and potatoes, our pizzas and big plates of pasta, and our sweets and desserts! Not everyone, of course… but most people. Consequently, we are all as deficient in folate as we are in vitamin D. We are all as deficient in unprocessed fats and fat-soluble vitamins as we are in all other essential micronutrients. How depressing.

But once we know this, once we have been made aware of this situation, we can correct the problem by switching to a diet of whole foods—of real foods—rich in folic acid and fat-soluble vitamins like A, D, E and K2, (the inuits, for example, get all their vitamin D and the other fat-soluble vitamins from the fat of the whales and seals they eat), and supplementing adequately to maintain optimal levels of both vitamin D (80-100 ng/ml or 200-250 nmol/L) and folate (>5 ng/ml or >11 nmol/l), especially during conception, pregnancy and early childhood, but throughout life and into old age.

There’s one last thing I wanted to mention before closing, and in which you might also be interested: can we ask if one is more important then the other, folate or vitamin D, and do we have a way to answer this question from an evolutionary standpoint? Well, here is something that suggests an answer: in all races of humans on Earth, women are on average about 3% lighter in skin colour than men of the same group. For decades, researchers (mostly old men, of course) were satisfied with the conclusion that this was the result of sexual selection, in the sense that men preferred lighter skinned women and so this is how things evolved over time. Of course, most of you will agree with me now that this just sounds like a cop-out or at best a shot in the dark from a possibly sexist male perspective.

Most of you will surely also agree that considering the question from the perspective of the importance of vitamin D versus folate is clearly more scientific in spirit than claiming sexual selection to explain the difference. And if women are lighter than men no matter where we look on Earth, this strongly suggests that it is either more difficult to build up and maintain good levels of vitamin D to ensure healthy offspring, or that it is more important. In today’s world, it certainly is true that it is far easier to have good levels of folate because even if you stay inside all day, as long as you eat leafy greens or drink green juice, your folate levels will easily be higher than the optimal minimum of 5 ng/ml, and probably much higher, like mine which are five time higher than that at 25 ng/ml.

So, for us today, especially if we eat greens, there is no question that we have to pay much closer attention to our vitamin D levels that tend to be way too low across the board all over the world. We can hypothesise that if we continue evolving over millennia following this indoors lifestyle that we have, humans everywhere will continue to lose both body hair and pigmentation, even those who live in sunny countries, because they don’t expose themselves to the Sun. I would like to encourage you to instead expose your skin to the amount of sunlight that is in accord with your complexion, drink green juice, monitor your vitamin D levels at least once per year, and take supplements to ensure both stay in the optimal range (I recommend taking A-D-K2 together to ensure balance between them, better absorption and physiological action). That alone, even if you don’t do anything else, will be of great benefit to you, and, if you are a soon-to-be or would-like-to-be mother, of even greater benefit to your child or children.

And next time you go out, and each time after that, pay attention, look and appreciate the amazing richness and beauty of all the different skin colours and unique physical features of all the people you see all around. What you will be seeing is the inestimable richness and incalculable pricelessness of our collective human ancestry expressing itself vividly and openly, nothing held back and nothing hidden, for everyone to see and appreciate.

If you are interested in reading more about the topics touched upon in this article, its contents draw from the books Life in the Universe, Rare Earth, Masters of the Planet, The Story of the Human Body and the Scientific American special issue Evolution that features the article, entitled Skin Deep, that prompted me to write this post. And please share this post: we all need to do what we can to help overcome discrimination based on race and appearance.

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