Insulin and Triglycerides

Every time I review someone’s blood test results, and then discuss with them what they mean and what they should do to improve their numbers, there’s something I almost always have to explain. And this was the relationship between fasting insulin and triglyceride levels.

Take a look at this plot:

trigs_vs_insulin_gb

Plot showing ten pairs of measurements of insulin and triglycerides, made from the same blood samples. They were collected between 2011 and 2017, and all are from my own blood tests.

It shows measurements of insulin concentration on the horizontal axis in mili units per millilitre (mIU/ml), and triglyceride levels on the vertical axis in milligrammes per decilitre (mg/dl). This is a correlation plot in which independent measurements of one variable are plotted against independent measurements of another in an attempt to see if there is a relationship between them.

Is there an order in the way the dots are organized? They are clearly not randomly distributed as a circular cloud of dots—it would mean that there is no relationship. Instead, we see what looks like a linear relationship in which lower values of insulin correspond to lower values of triglycerides, and higher values of insulin correspond to higher values of triglycerides. It’s not a straight line, but it’s definitely a clear linear relationship, and the value of the correlation coefficient, which quantifies how tight the relationship actually is, of just under 0.9 is pretty close to 1. In other words, it’s a pretty tight linear relationship.

Triglyceride is a fancy word for fat or lipid, because fat molecules are composed of three fatty acids held together by a glycerol structure. This is what triglyceride refers to. The amount of fat in the blood is affected by the amount of fat we eat, and the amount of body fat we have. Naturally, after a fatty meal, triglyceride levels will increase as the fat goes from the digestive system into the blood, they will reach a maximum, and then start to go down. The longer we wait before we eat again, the lower they will go. But there’s a few complications.

The first is that depending on the amount of insulin, one of whose jobs it is to transport nutrients into cells, whatever is circulating in the blood—and this includes glucose, of course, but also protein and fat—will in general be stored away faster if insulin is higher, and slower if insulin is lower. This means that if you eat fat together with sugar or starch, the whole lot will be packed away, and mostly as fat, minus the little bit of glucose your muscles and liver have room to store up as glycogen.

The second is that depending on the state of insulin sensitivity—the fundamental parameter that determines how well or poorly cells can use fat for fuel—triglycerides will in general be used up faster if we are more insulin sensitive and slower if we are more insulin resistant. This means that in the morning, twelve to fourteen hours after having had the exact same meal, the more insulin sensitive person will have lower triglyceride levels than the more insulin resistant.

And in fact, no matter if we have a measure of fasting insulin or not, and no matter how little we know about the person’s overall health, fasting triglyceride concentration is probably the best general marker of insulin sensitivity. Nevertheless, because their levels fluctuate quite a lot over the course of each day as a function of what we eat and drink, it is true for triglyceride levels as it is true for many other blood tests that are affected by the kind and amount of food and drink we’ve had over the last days, and most importantly by the amount of sweet or starchy carbohydrates.

Now, take a look at this second plot:

trigs_vs_insulin_final

Plot showing, in addition to the 10 points shown in the first plot (in red), another 20 pairs of measurements of insulin and triglycerides, also all from the same blood samples, but from seven other persons.

It shows the same 10 data points shown in the first plot from my own results, but with another 20 pairs of measurements taken from other people that I’ve coached and helped with the interpretation of their results. You can see that the relationship is better defined because of the additional points that now together cover a wider range of values on both axes.

However, you can also see that, the relationship is not as tight. In particular, there are a few points that are quite far off the main trend—mostly those at the top of the plot with high triglyceride and low insulin values. We see how these off-trend points affect the tightness of the relationship seen in the initial data set when we compare the values of the correlation coefficients. These off-trend points lead us to the third complication I wanted to bring up.

But first, please take a minute to consider the matter: What could lead to having low insulin and at the same time high triglycerides? What could be the cause of the difference between my numbers, which did contain some very low insulin levels, but all of which were paired with equally low triglyceride values, and this other person’s numbers? What causes insulin to go down? What happens when insulin is low? What could cause triglycerides to go up while insulin is low?

Insulin, no matter how high it is, will start to go down when we stop eating. The longer we fast, the lower it will go. Each person’s baseline will be a little different depending mainly on their metabolic health and their body fat stores. The more efficient the metabolism is at using fat for fuel—the more insulin sensitive, the lower insulin will go. But also the lower the body fat stores are, the lower insulin will go. On the flip side, the more insulin resistant and the fatter we are, the longer it will take for insulin to drop and the higher it will stay at baseline.

This is pretty shitty. I mean, as we develop insulin resistance, average insulin levels will become higher and higher. As a result we’ll store calories into our growing fat cells more and more easily, and will therefore become fatter and fatter, faster and faster. But fat cells also secrete insulin! So, the more fat cells there are, the higher the insulin levels will be, and the harder it will be to lower our basal insulin. To burn fat, we need to lower insulin levels. The fatter we are, the higher the insulin levels will tend to be. And the fatter we are, the harder it will be to lower insulin levels.

It’s a bit of a catch, but in the end, it’s not such a big deal because basically everyone who is overweight and who starts to fast and restrict carbohydrates melts their fat stores away very well. It works incrementally: insulin goes down a little, insulin resistance is reduced a little, fat-burning starts; insulin goes down a little lower, insulin resistance is further reduced, fat-burning increases; and on it goes, until we have lost all those extra kilos of fat that we were carrying on our body, be it 5, 15, 20, 35, 60 or even 100 kg of fat! It’s just a matter of time.

Now, after this little tangent on insulin and fat stores, we can come back to those anomalous points in the plot, the most conspicuous of which is the one just below 120 mg/dl of triglycerides but only 3 mUI/ml of insulin. Have you come up with an explanation? Here it mine:

That point is from one of my wife’s blood tests. It is unusual because it was done after 24 hours of fasting. My 24-hour fasting blood test done a number of weeks before, and my numbers were 41 for trigs at 2.3 for insulin. The difference between her and I was that I was already very lean, whereas she wasn’t. Therefore, as she fasted, her insulin levels dropped very low, and then the body started releasing its fat stores into the bloodstream in high gear. This is why her triglyceride levels were this high while her insulin was that low. It’s almost certainly the same for the other two points up there with trigs at 110 and 90 with insulin around 4 and 2.5 (the latter one of which is also my wife’s).

Since we did many of our blood tests around the same time, there are 9 data points from her on the plot. Several are in the centre of the main trend at insulin values between 6 and 7, but I’d like draw your attention to her lowest insulin value that was measured at 1.8, and at which time her trigs were at 57, and her lowest triglyceride level of 48, at which time her insulin was at 2.2. This shows that on average her values are a little further along the trend than mine are because of the small difference in body fat, but that she has good insulin sensitivity, and a well-functioning metabolism that can efficiently use fat for fuel.

The other off-trend point, but in the other direction on the right hand side, with insulin just above 10 and trigs around 65, is from my mother’s first blood test which I ordered and included insulin and trigs, before I got her off carbs. She was 82 at the time, eating a regular kind of diet, but not a very nutritious or varied diet with plenty of bread and cheese, because she had serious problems moving around and taking care of herself while still living alone. And so, it’s just the result of being older, having plenty of carbs, but not being highly insulin resistant nor highly overweight. Her baseline insulin levels were just generally higher because of her age and diet, but her trigs weren’t excessively high.

However, after just four days of intermittent fasting on a very low carb regime with most calories coming coconut oil spiked green juices and coconut milk smoothies, her insulin went from 10.3 to 4.7, and she lost 5 kilos, which, of course, were mostly from the release of water that the body was retaining to counter the effects of the chronic inflammation that immediately went down with the very-low carb regime and fasting.

Later, having sustained this strict green healing protocol for about 6 weeks, her numbers were at 2.9 for insulin and 56 for trigs. And by then she had lost another 5 kg, but this was now mostly fat. She had, at that point, recovered full insulin sensitivity, had lost most of her body fat stores, and overhauled her metabolism. She was 83 at that time, which shows that this sort of resetting of the metabolism can work at any age.

On this note, let’s conclude with these take-home messages:

First, the next time you get a blood test, request that insulin and triglycerides be measured, because it’s the only way to know what your fasting insulin actually is, and because it is very telling of your level of insulin resistance or sensitivity, overall metabolic health, as well as your average rate of ageing as we’ve seen in a previous post on insulin and the genetics of longevity.

Second, when you get the results back, you will be able to tell from your triglycerides concentration, in light of your insulin level, either how well the body is using fat for fuel—in the case you are already lean, or how fast you are burning your fat stores—in the case you still have excess body fat to burn through.

And third, resetting metabolic health can be done at any time and at any age, and is yet another thing that shows us how incredible our body is—the more we learn generally or individually, the more amazing it reveals itself to be.

Rejecting the lipid hypothesis with a cholesterol of 278 mg/dl and a smile

When it comes to evaluating how likely you are to have a heart attack, the most accurate diagnostic—the gold standard—is the calcium score. The reason why it’s the most accurate is because it’s calculated from an actual 3D image of the heart and the blood vessels around it. A computerised tomography (CT) scan is done, and from it the amount of plaque buildup in all the places where it appears because of the high density of the calcium it contains is measured and summed to give the total calcium score.

3d_image_of_my_heart

3D volume rendering of my heart seen from the top.

This is the closest thing we have to a direct measurement of the amount of plaque in the network of arteries around the heart. From doing this to thousands of people, we know that plaque usually begins to accumulate after the age of 35. Why isn’t the calcium score test done systematically on everyone above 40 in order to assess their immediate risk, but also to track their individual cardiovascular evolution, showing, with a reliable reference each year, how quickly or slowly arterial plaque is growing? Because it’s too expensive. Therefore, it’s only prescribed to people who are deemed to be at high risk based on other so-called “risk factors”. You know the list: overweight, sedentary, smoking, stressed, etc. But the clincher in this list of risk factors, the one factor that has pretty much eclipsed all the other ones, at least for the past few decades, is high cholesterol.

The focus on cholesterol was, over time, shifted to LDL, the “bad” cholesterol, and later on the ratio between it and HDL, the “good” cholesterol, terms introduced by the pharmaceutical industry to convince us that there is a battle between a good guy and a villain that must be stopped, which they can help with by providing us cholesterol lowering statins, even if with each passing year, the evidence exonerating cholesterol and lipoproteins from any wrong-doing in the genesis and progression of cardiovascular disease has been accumulating. Still, for people and for doctors, it’s really hard to overcome the several decades of conditioning we’ve suffered holding cholesterol as the main culprit for heart disease.

Fortunately, this knowledge and information have been shared and available for as long as the first experiments that set us on this damning direction in thinking and mindset. For my part, I first read a clear expose on the function of cholesterol and lipoproteins from Ron Rosedale over 10 years ago. Then I read it from Uffe Ravnskov, then from Anthony Colpo, then from Malcolm Kendrick who has and to this day continues to investigate the topic and share his findings on his blog, and then from Gary Taubes. All of this has taught me that cholesterol, HDL, and LDL, are not only not dangerous, but that they are essential and crucial for optimal health. This, I shared with you in late 2011 in But what about cholesterol? and shaped my diet to maintain good healthy levels: I restricted carbohydrates and polyunsaturated oils, and have gotten most of my calories from minimally processed saturated fats from grass fed animals fats, coconut oil, butter, and olive oil. In this endeavour to maintain strong cholesterol and lipoprotein levels, as you can see below, I have succeeded.

The following plot shows all the measurements of total cholesterol I have ever gotten made from blood tests over the past decade. What you can see is that in late 2007—a time before which I ate mostly complex carbohydrates and polyunsaturated seed oils while avoiding animal and saturated fats—my total cholesterol was below 150 mg/dl. Since then, it has been generally around or above 200 mg/dl with a slight upward trend over the years.

ts_total

My own total cholesterol levels in mg/dl measured from late 2007 to mid 2018.

If we look at the concentration of low and high density lipoproteins LDL and HDL, we also see consistently high levels, with LDL typically 10-30 mg/dl higher than HDL levels. Unsurprisingly, the same general shape and trend are is seen in these measurements as are seen in those of the total cholesterol.

ts_hdl_ldl

My own LDL and HDL levels in mg/dl measured from late 2007 to mid 2018.

Many of you have been reading this blog for a while, and I trust that you have therefore also known for a while that cholesterol is good for you, and that we should strive to have robust levels of HDL, LDL, and total cholesterol. Whether you have managed to overcome the conditioning we have all been subject to over our lifetimes about the purported but never-substantiated dangers of cholesterol and saturated fats, I cannot know. But I hope that I have at least helped a little in that respect.

In any case, I have for several years, every since I first read about the calcium score, wanted to get this test done, and see where I actually stood on the arterial calcification scale. I’ve never had fears or apprehension about it because even when I first read about it, I felt that I had a pretty good idea of the process by which cardiovascular disease evolved, and was following a regime that I knew would minimise the likelihood of atherosclerosis. But still, there is a big difference between having confidence that something is the case, and actually knowing that it is by seeing observational, quantitative, measured evidence for it. Finally, this spring, I was able to get a calcium score done.

I was very lucky to be referred to a young (45), well-informed, and open-minded cardiologist who also does research and has led trials on a group of several thousands of people who work at the Santander Bank campus near Madrid. He also happens to be the head of the cardiology imaging unit of the Clinical Hospital San Carlos in Madrid, a post he has held for more than 6 years now. So, he’s not just any cardiologist: he’s one of the best, and most importantly, one of the very best in cardiology imaging, which was exactly the purpose of consulting with him in the first place. I could not have been in better hands.

On our first appointment, after the initial conversation and questions regarding medical and health history, his assistant helped do an ECG, which looked “perfectly normal”, he said. Then he did the ultrasound with Doppler imaging that allows to see the heart pumping and the blood flowing with a colour coding of red and blue for the blood flowing away and towards the probe. To the trained eye of the imaging cardiologist, the Doppler ultrasound shows how the heart moves, how the cross-sections of the arteries pulsate with the heart beats, how the valves open and close, how flexible the tissues are, and how impeded or unimpeded the flow is. After a thorough examination, from one side and then from the other, he said everything looked very good.

At the end of the appointment he wrote a prescription for the CT scan to be able to get my calcium score, and another for a set of blood tests to which he willingly allowed me to request any additional one I wanted to have done. Before leaving the clinic, the assistant was able to arrange to have the blood test and the scan on the same day one week later: the blood test would be done in house first thing in the morning, and the scan would be done afterwards at the best medical imaging facility in the city.

The day before the scan, I read up on the test, how it’s done, how the measurements are made, and what the score means. I found out that, first, that the measuring of the amount of plaque buildup was done by eye, meaning that the experience and know-how of the cardiologist doing it was quite important. Second, I found out that the scale was not normalised like a scale from 1 to 10 or 0 to 100; that it was from 0 to whatever, which could be 400, 1000 or 4000. Although I was surprised and a little disappointed at first—we all love to get a score that can be immediately compared to everyone else’s, and gives us a sense of where we stand with respect to the rest of the population—I quickly realised that this made good sense given that it is not a relative but instead an absolute measure of plaque buildup in the arteries: naturally, this can go from no plaque to a little bit, to a lot, and to a ton of plaque. One could imagine estimating a maximum amount—say the amount needed to completely fill up the arteries—and use that as the normalising factor representative of 100%, and expressing every other result with respect to this. For now, this hasn’t been done, and the guidelines for interpreting your calcium score suggest values as follows:

  • 0 — No identifiable plaque. Risk: Very low, generally less than 5 percent.
  • 1 – 10 — Minimal identifiable plaque. Risk: Very unlikely, less than 10 percent.
  • 11 – 100 — Definite, at least mild atherosclerotic plaque. Risk: Mild or minimal coronary narrowing likely.
  • 101 – 400 — Definite, at least moderate atherosclerotic plaque. Risk: Mild coronary artery disease highly likely, significant narrowings possible.
  • 401 or Higher — Extensive atherosclerotic plaque. Risk: High likelihood of at least one significant coronary narrowing.

I got the blood test results back before the calcium score: everything looked good. Because most of my blood markers have been stable for years, especially the metabolic markers related to glucose and fat metabolism, the ones I am most interested in are those I need to monitor: things like B12, folate, homocysteine, and D, all of which need to be controlled and their levels adjusted with supplements; those that show my hormonal status, especially for the thyroid and sex hormones; and finally the markers of systemic inflammation which should always be as low as possible. The cholesterol panel is the one that for me has the least importance. But we are here considering cholesterol and lipoproteins in relation to cardiovascular risk assessed by means of the calcium score. So, these were the measured values: total cholesterol was 278 mg/dl, HDL was 122 mg/dl, LDL was 145 mg/dl, VLDL was 11 mg/dl (ref: <40), lipoprotein(a) was 4.40 mg/dl (ref: <30), and the ratios of total/HDL and LDL/HDL labelled atherogenesis indices were 2.28 (ref: <4.5) and 1.19 (ref: <3.55), values which are all deemed very good, of course.

A few days later I got my calcium score back. What do you think it was? You know I’m currently 45 and that calcification begins to grow after the age of 30-35, and has definitely progressed by the age of 40. You also know that—from what we are told by most doctors and health authorities—that plaque buildup and calcification is an inevitable part of ageing, that no matter what we do or eat or not eat, even if we might be able do things to slow it down, plaque accumulates and calcification progresses in only one direction: upward and onward. With this in mind, what would you guess my calcium score was?

My calcium score—based on 3D imaging of the heart and the region around it, and calculated by the one of best imaging cardiologist in Spain—was 0. It wasn’t 10 or 20. It wasn’t even 1, or 2, or 3. It was zero.

In our scientific training we learn that theories can never be proven—that they can only be disproven, and that hypotheses can never of accepted—that they can only be rejected. We also learn that to disprove or reject a theory or hypothesis, what is needed is a single contradicting piece of evidence, a single contradicting observation. The lipid hypothesis—that elevated blood cholesterol leads to atherosclerosis of the arteries, and that therefore decreasing blood cholesterol concentration significantly reduces cardiovascular risk—has been ingrained into our psyche more solidly than almost anything else that we collectively believe. But faced with this evidence, even if it is from one person only, of having maintained “elevated” fasting cholesterol levels consistently for a decade while in spite of this having gotten a perfect calcium score at the age of 45, the hypothesis must surely be rejected.

Even if we didn’t have any other evidence at all, according to the scientific principle that one contradicting piece of evidence is sufficient to reject a hypothesis, this single instance of my history of high total cholesterol together with a calcium score of zero is enough to reject the hypothesis that having elevated blood cholesterol levels over a long time leads to atherosclerosis and therefore to cardiovascular disease.

And we can be sure I’m not the only one. In fact, I’m willing to bet anything that most people in the low carb community who have been low carbers for as long as I have will have high cholesterol levels and low calcium scores. But still, to change the mindset of several generations of doctors, journalists, and people everywhere—hundreds of millions of educated people conditioned from decades of misinformation—will take years, probably decades. That’s how we are as social animals: stubborn in our beliefs.

In any case, I hope you, at least are, if you weren’t already, are now convinced that having high cholesterol does not cause atherosclerosis. Are you now curious to find out what your calcium score is? If you do get it done, please share.

For my part, I feel even more confident than I did. Even if I assured you more than five years ago in the spring of 2013 in At the heart of heart disease that you could be entirely free from cardiovascular disease by following some basic guidelines I listed regarding our eating, drinking, and living habits, there is nothing like observational evidence. And now we have it.

Case study: B12 deficiency, rapid weight loss, protein in the urine, osteoarthritis, elevated vitamin D

Just last week, a friend of mine wrote me this:

My mom has not been well.  Not eating well, massive head ache, lost a lot of weight.  Blood test results yesterday showed that she’s B12 deficient;  urine, however, has too much protein.  Any idea why?

I suppose, since he asked me, it most likely meant her MD didn’t offer an explanation for the test results.  One this is sure, neither she nor he knew what to do.  My feeling is that he asked just in case I knew anything that could help. And I did. So, I did.

Let’s go through the analysis together:

case_study_analysis

Is it normal to have protein in the urine?  What is supposed to be excreted in the urine?  What organ regulates what goes and what doesn’t go into the urine?  Under what circumstances would protein end up in the urine?

From a biological standpoint protein is precious.  From an evolutionary standpoint protein is hard to come by and hence relatively rare.  Therefore, the body has evolved to use and keep as much protein as it can.  The urine is intended to excrete uric acid, which is the main acid produced by metabolic processes.  Urine is excreted through the urethra, it is stored in the bladder, and it is produced by the kidneys, which filter the acids out of the blood.  The kidneys try to prevent large molecules like amino acids and glucose from going through into the urine.  The solids in the blood are separated from the water, the acid is filtered out of it, and depending on the state of hydration, more or less water is used to make urine or returned back to the blood.  The only circumstances under which protein would end up in the urine are 1) that the kidneys are not working properly, and unable to filter the protein out of the blood, 2) that there is a serious excess of protein in the blood, or 3) that there is both kidney dysfunction and excess amino acids in the blood.  We’ve explored kidney function in great detail before in The kidney: evolutionary marvel, and this understanding comes from there.

This means we already know that his mom either has kidney disease, that there is too much protein in the blood, or both.  But he wrote that she had lost a lot of weight.  Losing weight can be due to fat loss, muscle loss, or both.  Usually, very rapid weight loss in the elderly is not voluntary, and almost always means rapid loss of fat and muscle.  Therefore, for sure, the protein in the urine was the result of a the fast weight loss with rapid breakdown of muscle tissue.

But why?  Why would she all of a sudden start losing weight so fast?  What could have happened or triggered this?

Well, he also wrote that she was found to be B12 deficient.  And if this was recognized by the conventional MD who ordered the tests, you can be sure B12 levels were very low: surely below 200 pg/ml.

Do we become B12 deficient all of a sudden?  Or do B12 levels decrease slowly and gradually over the years?  Can we even become B12 deficient all of a sudden?  Why do we become B12 deficient in the first place?  And why is B12 important and relevant in this case?

It is possible to become B12 deficient all of a sudden.  This happens when our levels are marginally acceptable to start, and we receive a large dose of an anesthetic, before a surgery, for example.  Anaesthetic drugs deplete B12; and the larger the dose, the more severe the depletion.  But this is certainly not the majority of cases.

Most of the time, B12 levels decrease slowly and gradually over the years,  either from inadequate intake, or from compromised digestion.  In the younger population, it is usually from inadequate intake—as is the case for vegans and vegetarians.  In older adults, it is usually from compromised digestion—as is the case from the middle aged to the elderly, generally from a damaged gut and stomach cells that do not produce enough hydrochloric acid needed to break down the protein we eat.

As some of you will remember, we’ve also explored the importance and functions of vitamin B12 in B12: your life depends on it and more recently in Case Study: Homocysteine, B12, and folate.  Vitamin B12 is most important for its role in the nervous system: for healthy nerves and proper brain function.  But it is also an important anabolic nutrient essential in building and preserving muscle tissue.  Bodybuilders everywhere have been taking B12 supplements for at least 4 decades, exactly because it’s a potent natural anabolic.

Therefore, here is where our analysis leads us:

The most probable explanation is that his mother has been growing more and more deficient over the years, a B12 deficiency developed over several decades that just recently reached critically low levels. This triggered rapid weight loss that caused both the loss of body fat stores and the breakdown of muscle tissue.  The fat loss released streams of toxins that have been accumulating in the fat cells over years and years, and which caused the massive head aches from which she was complaining.  The muscle loss, the rapid breakdown of muscle tissue due to the extreme B12 deficiency, caused the kidneys to be overwhelmed and become unable to keep all these amino acids in circulation, and the protein therefore spilled into the urine.

My recommendation: B12 shots of 1 mg once a week for 10 weeks, and then of 5 mg once a month for the rest of her life.

 

The story doesn’t end here.  It turns out that she has osteoarthritis and she’s in pain.  Some time ago some friends of hers recommended taking vitamin D supplements, and so she did.  When she got her blood test done, her 25-OH-D was through the roof at 127 ng/ml.  If you’ve read our last post on vitamin K2 you will know that this is possibly the worst thing that someone with arthritis can do: high levels of D without correspondingly high levels of K2 will accelerate soft tissue calcification.  And since osteoarthritis is a disease of calcification, it will make everything much worse than it already is.  Naturally, I immediately recommend she stop taking vitamin D and start taking large doses of vitamin K2 as soon as possible, before something more serious like a stroke or a heart attack happens.

He sent me the blood tests, which I examined to get a better picture.  Interestingly, few markers were out of the reference ranges.  This is probably why nobody said anything other than to point out the obvious abnormalities: low B12, high D, and protein in the urine.

But in addition, what could be seen was that both urea and creatinine were near the top of their range, which is expected from rapid weight (muscle) loss, and the eGFR (the estimated glomerular filtration rate) was at the low end of the reference range, which is expected from compromised kidney function given the protein in the urine.  C-reactive protein was high but not super high.  This signals system inflammation, and is naturally excepted for someone with arthritis, as we also have seen together in the past (https://healthfully.net/category/arthritis/).  Lastly, calcium was also high, but nevertheless within the reference range, something we would expected for someone with high D and not enough K2.

 

I asked if she was taking medications, and she was.  Several different drugs among which were a statin drug to lower cholesterol, a malaria drug used to treat symptoms of arthritis, and a couple of high blood pressure drugs one that is a diuretic and forces the kidneys to excrete more water, and the other that is an angiotensin antagonist that blocks the hormone which tells the kidneys to retain water when hydration is inadequate.  I replayed my view that drugs typically always attempt to block some pathway, and prevent the body from doing something that it naturally does to protect itself.  And in this case, she should wean herself off all of these over a few weeks.

I also explained that one of the most serious side effects of statin drugs is that they cause muscle wasting, promoting muscle tissue breakdown.  Statins do this in everyone, but in the elderly who already have accelerated muscle breakdown, it can be very serious.

My final recommendations, beside coming off the various drugs gradually to avoid a shock to the body, were as simple as possible for an old woman to follow: high dose B12 shots, high dose K2 pills, and high dose Mg as L-threonate, plenty of water and salt each day, a low carb diet rich in animal fats and green veggies, and sodium bicarbonate in water first thing in the morning on an empty stomach.  We’ll see what happens.

 

Blood tests can be used very effectively as a window onto the inner environment of the body.  MDs tend to only pay attention to the markers outside the reference range that appear in bold on the print outs.  But the reference range is derived from the blood tests of the whole population, and the population is far from being optimally healthy, that’s for sure.  What we need are not reference ranges derived from a sickly population, but an understanding of how the body works, what its organs and systems are trying to do, and with that understanding, of what our blood markers should be … ideally. What they should be in the best possible case.

That’s what we have to aim for.  And that’s what we have to learn to do, because we certainly can’t rely on your average MD to help us in this.  If you are an MD, and you are reading this, you already know that you are not your average MD, and I’m pretty confident you also know that your patients are lucky to have you.

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Reversing calcification and the miracle of vitamin K2

Vitamin K2 is the only known substance that can stop and reverse soft tissue calcification.

If you didn’t stop at the end of that sentence to say Wow to yourself, you should keep reading.

Soft tissue calcification is one of the most serious health problems we face as individuals, as modern societies, and, on a global scale, as a species.  Cardiovascular disease—which leads to heart attacks and strokes, and accounts for nearly half of all deaths in industrialised countries—is a disease of soft tissue calcification: the calcification of our arteries.

Arthritis, of which basically everyone past the age of 40 suffers, and increasingly more with time and with age, is a disease of soft tissue calcification.  It is caused by the calcification of the cartilage in the joints:  the joints of the knees, but also of the shoulders; the joints of the hips, but also of the wrists; the joints of the elbows, but also of the feet and the toes; the cartilage between the vertebrae of the neck and the spine all the way down the back, but also of the hands and of the fingers.

Soft tissue calcification also causes kidney stones and kidney disease.  How many people above the age of 60 don’t have kidney problems?  Hardly any.  And how many young men and women in their 20s and 30s already have kidney stones and kidney dysfunction?  More and more every year.

Every one of the processes generally associated with ageing, from heart disease and stroke, to Alzheimer’s and dementia, to arthritis and kidney disease, to stiffness in the joints and muscles, but also to the wrinkling of the skin, is intimately linked to soft tissue calcification.

And now, let me repeat the sentence with which we opened:  Vitamin K2 is the only known substance that can stop and reverse soft tissue calcification.  It is really remarkable.

 

Maybe you didn’t know about calcification.  And so, maybe you are wondering why it is such a major and widespread problem, why it affects everyone no matter where we are or what we do.  It’s a good question.  But because we know that only vitamin K2 can prevent this from happening, we already have our answer:  soft tissue calcification is a major and widespread problem because our intake of vitamin K2 is inadequate to provide protection from calcification.

Naturally, the next question is why?  Why is our intake of vitamin K2 so inadequate?  If it is such a crucial essential nutrient, we would surely not be here as a species if intake had always been so inadequate.  Looking at things the other way around, if we are so dependent on adequate K2 intake for staying healthy, this must necessarily mean that we evolved having plenty of it in our food supply.  What’s so different now?

To answer this question with some level of detail—meaning with an explanation more extensive than just saying that it’s industrialisation that stripped our food supply of vitamin K2 as it has for all the essential nutrients to a greater or lesser extent—we have to understand what K2 is, how it’s made, and where it’s found in food.

 

The short answer is that K2 is found in the fat of pastured animals that graze on fresh green grass, and produced from vitamin K1 by certain kinds of bacteria in their gut.

The longer answer is that vitamin K2 is a family of compounds called menaquinones, ranging from MK-4 to MK-13 depending on their molecular structure.  These compounds are derived from the plant analog, the sister compound, vitamin K1, called phylloquinone, and found in chlorophyll-rich plant foods.  Phylloquinone is consumed by the pastured animal, it makes its way into their intestines, and there it is transformed by the bacteria of the animal’s intestinal flora.  The resulting menaquinone is then stored in the fat cells of the animal as well as in the fat of their milk if they are milk-producing.  Consuming these animal fats in which vitamin K2 has been concentrated will provide this precious essential micronutrient.

If the grazing animal does not feed on green grass, they get no vitamin K1.  If they get no vitamin K1, their gut flora is not only compromised and negatively altered with respect to what it should be if they were consuming the grass they have evolved eating, but it produces no vitamin K2.  If their gut flora produces no vitamin K2, their fat and milk will contain no vitamin K2, and neither their offspring nor any person consuming products derived from the animal will get any vitamin K2.  Hence, no grass feeding, no vitamin K2 in the animal’s fat.

 

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It is most natural that grass-eating animals should be grazing on fresh green grass in open pastures.  And yet, it is rather rare.  But without green grass, there is no vitamin K1.  And without vitamin K1 there can be no vitamin K2.

 

Maybe you’ve already thought ahead, and wondered since it is bacteria that produces vitamin K2 from vitamin K1 in the guts of grazing animals, can’t we make vitamin K2 without the need for grass-fed animals to do it for us?  Yes, it is possible.  Fermented vegetables and dairy products like cheese can also contain vitamin K2.  In fact, in the case of cheese, there is a lot more in the finished hard cheese than in the milk used to make it.  The amount varies widely because it depends on the kind of bacteria.  For dairy products, hard cheeses like Gouda have the most, and for plant foods, even if fermented veggies have a little, the Japanese fermented soybean snack natto is the ultimate source of K2.

As we all know, pastured meat and dairy is not easy to come by in our modern world.  It’s actually quite hard to find.  Our supermarkets and food stores are flooded with industrially produced meat and dairy from animals that have never seen a blade of grass—grass-grazing animals living their entire lives indoors, in stalls, fed and fattened exclusively on grains, corn, and soybeans.  This is how we have stripped our food supply of vitamin K2, and this is why is this a modern phenomenon—most of our grand-parents were still eating pastured meats and animal foods.

And if this wasn’t enough of a blow to vitamin K2 status, trans-fats, which are formed when vegetable oils are hydrogenated to be made saturated and stable (for long shelf life), and which most of us consume in great quantities, contain a K2 analog called DHP (dihydrophylloquinone) that displaces the little K2 that might has found its way into our diet.

It is for all these reasons that soft tissue calcification is so widespread.  And you have at this point what you need to know in order to first stop the process by which your soft tissues are getting increasingly calcified, and then, in time, to remove the accumulated calcium from these tissues.  It’s simple: healthy grass-fed animals produce yellow butter, yellow yolks, and yellowish fat;  you need to eat plenty of pastured animal foods, making sure you eat the fat in which vitamin K2 is concentrated, and, to be sure you have enough to reverse the already present calcification, take K2 supplements.  And this might be enough for you.

If it is, you can head to your browser to find and order some K2 supplements (I currently get mine, it’s a 500 mcg per tablet, from Phoenix Nutrition).  Also, we need to know that the two main forms of K2 are MK-4 (with four double bonds) and MK-7 (with seven).  The first is the one generally found in animal fats that haven’t been fermented, while the second is the product of bacterial fermentation.  Hence, meat and butter contain mostly MK-4, whereas natto, sauerkraut, and cheese contain mostly MK-7.

There is an important difference between these two forms of K2 in terms of their effects inside the body which has to do with their half-life, not in the sense of radioactivity, but in the sense of duration of biological activity in the body.  MK-4 will be in circulation at therapeutic doses for a number of hours, while MK-7 remains in circulation between 24 and 48 hours.  Therefore, to be safe, we need to eat grass fed meat and butter, and take MK-7 supplements (I take 1000 mcg), always after a meal with plenty of fat to maximize absorption.

 

If you are curious to find out more, if you want to know how menaquinone does this, how vitamin K2 does its miracles inside the body, then we need to take a closer look at the biochemistry of calcium metabolism.

There are three proteins found in bone matrix that undergo gamma-carboxylation via Vitamin K-dependent enzymes: matrix-gla-protein (MGP) (Price et al., 1983), osteocalcin (bone gla-protein, BGP) (Price et al., 1976), both of which are made by bone cells, and protein S (made primarily in the liver but also made by osteogenic cells) (Maillard et al., 1992) (Table V).  The presence of di-carboxylic glutamyl (gla) residues confers calcium-binding properties to these proteins.

MGP is found in many connective tissues and is highly expressed in cartilage.  It appears that the physiological role of MGP is to act as an inhibitor of mineral deposition.  MGP-deficient mice develop calcification in extraskeletal sites such as in the aorta (Luo et al., 1997).  Interestingly, the vascular calcification proceeds via transition of vascular smooth muscle cells into chondrocytes, which subsequently hypertrophy (El-Maadawy et al., 2003).  In humans, mutations in MGP have been also been associated with excessive cartilage calcification (Keutel syndrome, OMIM 245150).

Whereas MGP is broadly expressed, osteocalcin is somewhat bone specific, although messenger RNA (mRNA) has been found in platelets and megakaryocytes (Thiede et al., 1994).  Osteocalcin-deficient mice are reported to have increased bone mineral density compared with normal (Ducy et al., 1996).  In human bone, it is concentrated in osteocytes, and its release may be a signal in the bone-turnover cascade (Kasai et al., 1994).  Osteocalcin measurements in serum have proved valuable as a marker of bone turnover in metabolic disease states.  Interestingly, it has been recently suggested that osteocalcin also acts as a hormone that influences energy metabolism by regulating insulin secretion, beta-cell proliferation, and serum triglyceride (Lee et al., 2007).

These are the first three paragraphs of the chapter Noncollagenous Bone Matrix Proteins in Principles of Bone Biology (3rd ed.) which I found it on the web when I was searching for more info on the biochemical action of menaquinone.

And now, here is my simple explanation of how things work:

The players are the fat-soluble vitamins A, D, and K2;  three special proteins called osteocalcin, matrix gla protein, and protein S;  and an enzyme called vitamin K-dependent carboxylase.

First, vitamin D makes calcium available by allowing its absorption from the intestines into the bloodstream.  This is vital for life and health.  You know that severe vitamin D deficiency is extremely dangerous and develops into the disease that deforms bones called rickets.  Milder forms of vitamin D deficiency are much harder to detect without a blood test, but can and do lead to a huge spectrum of disorders and health problems.  However, without vitamin K2, ample or even just adequate levels of vitamin D will inevitably lead to increased soft tissue calcification.

Vitamins A and D make bone-building cells (osteoblasts) and teeth-building cells (odontoblasts) produce osteocalcin (also known as bone gla protein or BGP) and matrix gla protein (or MGP).  This is key because it is these proteins that will transport the calcium.

Vitamin K2, through the action of the vitamin K-dependent carboxylase enzyme, activates bone and matrix gla proteins by changing their molecular structure which then allows them to bind and transport calcium.

Once activated, bone gla protein brings calcium (and other minerals) into the bones;  and matrix gla protein takes calcium out of the soft tissues like smooth muscle cells of arteries, but also organs, cartilage, skeletal muscles, and skin.  Without this K2-dependent activation, BGP and MGP remain inactive, and the calcium accumulates in soft tissues all over the body.

What completes the act, is that vitamin K2 activates protein S which oversees and helps the immune system clear out the stuff of arterial plaques that remains once the calcium making the plaques structurally stable has been taken out.  And, amazingly, protein S does this without triggering a large inflammatory response.

Even though it is quite straight forward when explained in this way, this understanding of vitamin K2 and its action in the body is really quite recent: in the last 20 years or so.  For one thing, it was only 10 years ago that Chris Masterjohn solved the 60-year old mystery of Weston A. Price’s X-Factor, correctly identifying it for the first time as vitamin K2. (You can read that for yourself here.)  And although some laboratory studies and experiments on vitamin K were done several decades ago, the majority are from the last 10 years (take a look at the references in Masterjohn’s paper.)

 

We’ll stop here for now.  But we’ll come back to vitamin K2 because there are so many other amazing things it does for our health.

This article was inspired by Dr. Kate Rheaume-Bleue’s book entitled Vitamin K2 and the Calcium Paradox.  If you think it could be useful to others, please Like and Share it.

Ten years of carbohydrate restriction: here’s why

It was almost exactly ten years ago, in March 2008, that I read Ron Rosedale’s Insulin and Its Metabolic Effects.  I now know that this is surely the one thing I’ve read that has had the most impact on my life. Rosedale’s presentation was a total revelation to me:  I had never read anything about insulin before, and his explanations of the biochemical and physiological functions and effects of insulin on the body all made perfect sense in and of themselves, but also appealed to my appreciation and reliance on complete explanations that are consistent with the facts we can observe about them.  I eliminated insulin-stimulating carbohydrates from my diet overnight.  That was that.

We were then still vegetarian at home.  Hence, the family breakfast, following Mercola’s example, became smoothies made of raw, local, pastured eggs with berries and stevia.  That lasted quite a while.  I always travelled with my hand blender and stevia, brought eggs if it was for short trip, or scouted out places to get good ones when the trip was longer.  Throughout a summer trip along the American west coast, I made our raw egg smoothies every day, in hotel rooms and campgrounds.

At one point, I discovered coconut oil and coconut milk.  The breakfast smoothies evolved to being made of eggs and coconut milk with berries, and eventually only coconut milk, berries and stevia.  This period lasted several years until we moved on to cold pressed green juice with coconut milk; it was two thirds juice and one third milk.  We also did this for several years until about two years ago when our son left for university, at which point we dropped having breakfast entirely to allow for a daily overnight fasting period of about 16 hours from after dinner to lunchtime.

 

Food intolerance testing in 2014 showed that all three of us were intolerant to eggs; we removed them from our diet.  My wife and I had the most and our son the least intolerances; this was not surprising given we were a lot older than him.  It also showed my wife and I were intolerant to most dairy products; we removed them from our diet.  We were also intolerant to grains: both highly intolerant to wheat, and then I, in addition, somewhat less so to barley, malt, and quinoa—we ate quinoa almost daily for years as our son was growing up.  He, although not intolerant to dairy or wheat, was intolerant to almonds, pistachios, and brazil nuts. (Here are my test results, if you’re interested.)

Imagine: vegetarian for 20 years, with a diet during these two decades from teenage hood to middle adult hood consisting primarily of wheat and grain products, beans, cheese and yogurt, eggs and nuts.  Of course, also plenty of sweet fruit, starchy vegetables, and salads, as with is true for most vegetarians.  But the bulk, both in volume and in calories, was from grain products, cheese, and eggs.  The shocker for me was that the food intolerance test painted the profile of a meat-eater:  if you remove grains, dairy, and eggs, what is left is animal flesh, vegetables and fruits.

If now, in addition, you remove fruit and starchy vegetables to avoid insulin-stimulating carbohydrates, all that is left is animal flesh and green vegetables.  That’s just how it is.  We also used to eat almonds—the richest in magnesium, and brazil nuts—the richest in selenium, almost daily.  But because our son was intolerant to both and I was intolerant to brazil nuts, we removed those from our diet as well.

IMG_2275

 

These were all food intolerances; they were not allergies.  But they were nonetheless intolerances, some stronger, some weaker.  If you are concerned about health in the sense of being in the best state of health you can, then obviously you must not eat foods to which you are intolerant.  Otherwise, your immune system is triggered each time the offending molecules in those foods enter the gut and bloodstream.  This gradually but inevitably makes the intolerance greater, your system weaker, and body sicker.

Over these ten years, I’ve read quite a few books, articles, blog posts, and detailed discussions about health-related matters.  I’ve also experimented quite a bit with my own diet, and learned a great deal from that.  The other thing I’ve done a lot of, is have conversations with people about diet, nutrition, diseases, and the metabolic effects of different foods and of insulin.

My position—which has only grown stronger with time—is that the first and most fundamental pillar of optimal health is having a metabolism that runs on fat.  And this means keeping insulin levels low by restricting sugars and starches.  Not necessarily always, but most of the time, as in almost always.

The first question that people ask when they find out is why: Why do you not eat bread? Bread has forever been essential to humans.  I simply couldn’t live without bread.  Or, why don’t you eat potatoes, or rice, or pasta?  They’re so good!  I simply couldn’t live without potatoes and pasta.  And, you don’t even eat fruit? But isn’t fruit full of vitamins and minerals?

The way I have answered has depended on a lot of things: the setting, the atmosphere, the company, the time available, but most importantly on the person.  Some people are actually interested to find out, and maybe even learn something.  Most, however, are not.  Consequently, I have made the answer shorter and shorter over the years.  Now, I even sometimes say: well, just because, and smile.

Maybe you have wondered, or even still wonder why.  Maybe although you’ve read so many times in my writings that I think everyone seeking to improve their health should restrict insulin-stimulating carbohydrates, you still wonder what the main reason is, what the most fundamental reason for which I don’t eat sugars and starches.  Here’s why:

 

It’s not primarily because carbs and insulin make us fat by promoting storage and preventing the release of energy from the ever larger reserves of fat in our body: I am lean and always have been.

It’s not primarily because carbs and insulin lead to insulin resistance, metabolic syndrome, and diabetes; inflammation, dyslipidemia, water retention, and high blood pressure; kidney dysfunction, pancreatic dysfunction, and liver dysfunction: my fasting glucose, insulin, and triglycerides have been around 85 mg, 3 mili units, and 40 mg per dl for years; my blood pressure is 110/70 mg Hg, glomerular filtration rate is high, and all pancreatic and liver markers are optimal.

It’s not primarily because carbs and insulin promote cancer growth since cancer cells fuel their activity and rapid reproduction by developing some 10 times the number of insulin receptors as normal cells to capture all the glucose they can, fermenting it without oxygen to produce a little energy and tons of lactic acid, further acidifying the anaerobic environment in which they thrive.  My insulin levels are always low, and my metabolism has been running on fat in a highly oxygenated alkaline environment for a decade.

It’s not primarily because carbs and insulin promote atherosclerosis, heart disease and stroke by triggering hundreds of inflammatory pathways that compound into chronic inflammation and damage to the blood vessels, which then leads to plaque formation and accumulation, restriction of blood flow, and eventually to heart attack and stroke: my sedimentation rate, interleukin-6, C-reactive protein, and Apolipoprotein-A are all very low.

It’s not primarily because carbs and insulin promote the deterioration of the brain, dementia, and Alzheimer’s, both through the damage to blood vessels around and in the brain itself, and insulin resistance of brain cells, which together lead to restricted blood flow, energy and nutrient deficiency, and accumulation of damaging reactive oxygen species and toxins in the cells, and, unsurprisingly, eventually to dysfunction that just grows in time: because my metabolism runs on fat, this means that my brain runs on ketones, and is therefore free of excessive insulin or glucose exposure.

It isn’t primarily for any of these reasons, which, I believe, are each sufficient to motivate avoiding sugars and starches in order to keep tissue exposure to glucose and insulin as low as possible.

 

My main reason is that, at the cellular level, in its action on the nucleus and on gene expression, insulin is the primary regulator of the rate of ageing.

Insulin is essential for life: without insulin, cells starve and die. It is essential for growth: without insulin cells don’t reproduce, and there can be no growth.  This is why at that most fundamental level, insulin regulate growth in immature individuals.  But in mature individuals, once we have stopped growing, insulin is the primary regulator of the rate of ageing, both in terms of its effect in suppressing the production of antioxidants and cleansing and repair mechanisms within the cell, but also in stimulating cellular reproduction. And the more reproduction cycles, the greater accumulation of DNA transcription defects, the faster the shortening of telomeres, and the faster the ageing.

This is a fundamental fact that appears to be true for all living organisms.  It is as true for yeasts and worms, as it is for mice and rats, as it is for dogs and humans.  And the rate of ageing is the rate of degeneration, of growing dysfunction, of more damage and less repair, of lower metabolic efficiency and less energy, of increased cell death and senescence.  I personally wish to be as healthy, energetic, strong, and sharp as possible for as long as possible.  This is why I avoid sugars and starches.  This is why I restrict insulin-stimulating carbohydrates.

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How much water do you lose during a bath?

Have you ever wondered how much water you sweat out during a bath? Well, I often did. A few years ago, I had a very regular schedule in the morning because my wife and son had to leave early to make it to school in time.  I got up early to make the green juice for the three of us, but after they left at 7:30, I had plenty of time before going to work.

For a couple months during the winter, I had a bath twice a week.  They were therapeutic baths: I was correcting a long-standing whole body magnesium deficiency from decades of intense physical exercise without ever supplementing with Mg, or anything else for that matter.  I was curious to know, and so I tried to remember to weigh myself before and after each bath, and write that down.  I did it for a while, but I forgot everything about it.

A couple of days ago I did a complete cleanup of my closet, and found the little piece of paper on which I had written all the measurements.  I thought it would be fun to share that with you.

I tried to stick to the same conditions in terms of drinking and peeing, but I wouldn’t call it a tightly constrained scientific experiment. I made 15 measurements of my weight before and after soaking in the bath at about 45-47 C for approximately 45 minutes, and calculated the difference:

  1. 59.6  58.9  0.7
  2. 59.5  58.9  0.6
  3. 59.6  58.8  0.8
  4. 60.3  59.8  0.5
  5. 59.6  58.8  0.8
  6. 60.1  59.5  0.6
  7. 59.6  58.9  0.7
  8. 60.0  59.4  0.6
  9. 60.4  59.6  0.8
  10. 59.4  58.9  0.5
  11. 59.9  59.3  0.6
  12. 60.9  60.3  0.6
  13. 60.6  60.1  0.5
  14. 60.6  60.0  0.6
  15. 60.5  59.9  0.6

This is what the distribution of the differences looks like:

histo-diff

Frequency distribution of difference in body weight before and after bath. (The digital scale had one digit, and assuming the precision on each measurement is half that (0.05 kg), this would make the combined uncertainty on each calculated difference the square root of twice the square of that, and hence 0.07 kg.)

Given that there are various trends in our weight from day to day that depend on a wide range of factors, only the difference between the weight before and after the baths is important for us here. But because they all have the same uncertainty, it has no effect on the mean, which turns out to be 0.63 (9.5/15); the variance, which turns out to 0.01; and the error on the mean, which turns out to be 0.03. Hence the mean difference in weight before and after is 0.63 +/- 0.03 kg.

There would have certainly been variations in the temperature of the water, which could account for the variations in the before and after differences ranging between 0.5 and 0.8 kg. We could say that the hottest baths resulted in a water loss of 800 ml, whereas the more moderate temperatures caused a loss of 500 ml. In any case, as we said, the average of the 15 measurements is 0.63 kg, and this equates to 0.63 litres or 630 ml of water.

I think it is reasonable to consider this is in terms of the fraction of water loss with respect to body weight, which for me at the time would have been equivalent to about 1% of body weight. This is probably not precisely the case, but a good guideline to follow: if you weighed 80 kg, you should consider that a 45 minute bath would cause you to lose about 800 ml of water; if you were 100 kg it would cause you to sweat out a full litre.

And so, that’s it. The answer to the question of how much water we lose during a bath—or actually more specifically, during a bath in which the water is around 45 C, and in which we soak for 45 minutes, and in which we have dissolved 1 cup of baking soda and 1 cup of magnesium chloride—is about 1% of our body weight.  Very easy to remember.

Therefore, ideally, we would be sipping cool alkaline water throughout the bath to make up for that loss and minimize the dehydrating effects of that much sweating.

Have you ever done this on your own: weighed yourself before and after a bath to see how much water you lost? If you have, I’d be very curious to know what you found. If you haven’t but are intrigued, and want to do it, please go ahead and let us know.

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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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