The Vitamin D, Statin, and Cholesterol Paradox
Disclaimer
This post is not intended to diagnose or treat any disease. If you think you have a medical problem, see your doctor immediately.
This post is a bit heavy on science. If you want to get to the point, go to the last section called “Here’s what we know”
The major precursor of vitamin D is cholesterol. Without cholesterol, we cannot make it. Some people may find this shocking because vitamin D is highly praised, while cholesterol is demonized. Cholesterol's bad rap is tragic because it is vital for life. To illustrate this fact, Smith-Lemli-Opitz Syndrome, a rare disorder where people can't make enough cholesterol causes terrible symptoms. Cholesterol is a vital component of cellular membranes, a precursor to bile acids, steroids, and oxysterols, and is implicated in neurological development, cardiovascular health, innate immunity, and gallbladder disease. 1
Additionally, much of what we hear about the relationship between high cholesterol and heart disease is, at best, an exaggeration and, at worst, incorrect. You can read my posts about the confusion here, here, and especially here. Since vitamin D and cholesterol are so closely related, they have an interesting interplay. Statin drugs, which lower cholesterol, also take part in the interplay. The way they interact is understood, but some observations go against what scientists believe should happen based on our current understanding. In 2007 scientists produced the first paper, including a comprehensive diagram of the interaction between cholesterol and vitamin D. Vitamin D's importance in lowering heart disease is dismissed in the paper, while the effect of statin drugs is played up. Shocker. Some miscomprehension is due to knowledge gaps, and some (I believe) is due to hijacked science. In today's post, I will describe the interaction between cholesterol, vitamin D, and statins and give my two cents about why vitamin D is dismissed for heart disease treatment.
Vitamin D Precursor 7-Dehydrocholesterol
The pathway to vitamin D synthesis (the Kandutsch-Russell pathway) is the same as cholesterol for many "steps." I use the term step loosely because, as you can see on the diagram above, the few interwoven pathways are more like a web. About 80% of all cholesterol is made in our body, and dietary cholesterol makes up the rest. Contrary to popular belief, we down-regulate production when cholesterol is ingested, and studies show that dietary cholesterol does not change our cholesterol significantly. 2 Read my article on high-cholesterol diets here if you want more information. The vitamin D precursor is called 7-dehydrocholesterol. It is as close as two steps away from cholesterol or as far as four, depending on the pathway. Keep in mind that the pathways can go in both directions. Which direction depends on too many factors to include in this simplified post. For a better view of the diagram above, click here.
UV Light and Active Vitamin D
Vitamin D suppresses inflammatory responses in insulin resistance, April 2020, Berkala Ilmu Kedokteran 52(02), DOI: 10.19106/JMedSci005202202009
Only three steps are needed to convert 7-dehydrocholesterol to active vitamin D. UV light is needed to convert the 7-dehydrocholesterol to vitamin D3, called Cholecalciferol. The liver converts it to 25-hydroxy vitamin D or Calcidiol, the form measured on blood tests. The kidneys then convert calcidiol to active vitamin D or 1,25-Dihydroxycholecalciferol, also known as Calcitriol.
Vitamin D and Health
Read this post for more information on Vitamin D and health. In short, the medical profession has come to understand the importance of adequate vitamin D levels, and more of my patients are on supplemental vitamin D today compared to past years. Despite this, one study found that 77% of Americans are deficient in vitamin D. 3 Emerging research supports the role of vitamin D in fighting cancer, heart disease, fractures, falls, autoimmune diseases, influenza, type-2 diabetes, depression, and, yes, cavities. The most at-risk populations for deficiency are darker-skinned people, older adults, people with fat malabsorption, people with limited sun exposure, and people with gastric bypass. 4
Cholesterol's Bad Reputation is Exaggerated
For reasons too numerous to list in this post, high cholesterol is blamed for heart disease, while other causes are ignored. Furthermore, vegetable oils are credited for lowering cholesterol. Hence, they are assumed to help lower heart disease risk by proxy.
Many factors contribute to heart disease, and oxidized cholesterol is a major culprit, and you can read my post on the subject here. Sadly, only a few randomized controlled trials have ever tested the traditional diet-heart hypothesis for heart disease, yet it remains the gospel truth. Recently, researchers recovered unpublished data from the Sydney Diet Heart Study that showed that lowering cholesterol using vegetable oil rich in linoleic acid significantly increased the risks of death from coronary heart disease and all causes, despite lowering serum cholesterol. The Minnesota Coronary Experiment considered one of the most important studies supporting the saturated fat-heart disease connection, also underwent further scrutiny. It was the only randomized controlled trial to complete autopsies of patients with heart disease. According to the new perspective on the data, participants with a more significant reduction in serum cholesterol from the addition of linoleic acid had a higher rather than lower risk of death. 5 More recent research shows that cholesterol was protected from oxidation if bound to saturated fat but susceptible to oxidation when bound to linoleic acid. 6 Despite these recent findings, cholesterol-lowering drugs called statins remain a top seller. These two important studies refute high cholesterol as a risk factor for heart disease and identify oxidized cholesterol as a greater risk factor.
Statins and Coenzyme Q10
Statins decrease cholesterol production by blocking an enzyme needed for cholesterol production. Once again, by this proxy, the assumption is that with lower cholesterol comes less cardiac risk, which we have already seen is questionable. The popularity of statin drugs depends on the theory that high cholesterol causes heart disease. The enzyme statins block is active at step two, so we would expect less production of all molecules in the cholesterol pathway, like CoQ10. Statin-induced low CoQ10 can induce adverse effects like muscle pain, the most common being myositis, myopathy, and myalgia, and, less frequent but more severe, rhabdomyolysis, which is a rapid form of muscle breakdown that can lead to death through kidney failure. It has been estimated that 10–15% of statin therapy patients experience such effects. Strangely, statins are credited with anti-inflammatory effects despite all the pain they promote. 7 For more on CoQ10, read this post.
Vitamin D and Heart Disease
Vitamin D supplementation has been shown to lower total and LDL (the bad one) cholesterol and triglycerides (high is bad). Conversely, low vitamin D status is linked to higher total and LDL cholesterol, lower HDL (the good one), and higher triglycerides (bad for you). A high triglyceride to HDL ratio is a statistically relevant risk factor for predicting heart disease, so this makes sense. In summary, low vitamin D is associated with an increased risk of heart disease. Lastly, vitamin D supplementation in patients receiving atorvastatin(a statin) treatment has been shown to lower total cholesterol and LDL-C even further, which agrees with the mechanisms scientists understand. 8
The Vitamin D Paradox
Since vitamin D depends on cholesterol for its formation, one would assume that statins lower vitamin D. It does not. Furthermore, it has been observed that vitamin D supplementation reduces the side effects associated with statin treatment and the concentration of the statin and its metabolites while enhancing its action. The mechanisms in place today would predict vitamin D to lower CoQ10 further, but this is not the case!
Vitamin D, however, is well known to reduce inflammation. Strangely the anti-inflammatory mechanism of vitamin D works as expected, while statins do the opposite. Scientists are scratching their heads over all of this. I am not. Let me elaborate.
Statistics and Proxies
If one believes high cholesterol is the main driver of heart disease, lowering it with statins makes sense. Indeed, this is the reason why your doctor promotes statins and low cholesterol. They promote the proxy, not the dismal outcome of statin use. Last March, researchers found that statins only reduced the absolute risk of death by 0.8%, 1.3% for heart attacks, and 0.4% for strokes in those randomized to treatment with statins compared with control! Proxies help their case, which is as flimsy as a house of cards. Furthermore, in 2020, researchers warned, "Setting targets for 'bad' (LDL) cholesterol levels to ward off heart disease and death in those at risk might seem intuitive, but decades of research have failed to show any consistent benefit for this approach.” 9
Scientists and companies use bogus relative risk reductions to promote all pharmaceutical products. Using the trick of relative risk reduction, the .8% lower risk of death while on statins increases to 9%, the 1.3% lower risk of a heart attack jumps to 29%, and strokes go from 0.4% to 14%. Relative risk is a statistical sleight-of-hand. Please don't fall for it! Read this post to learn how to interpret statistics properly.
The Study of Disease is Diseased
What needs to be clarified is why vitamin D does the same and gets zero credit for reducing heart disease and why it is not accorded the same courtesy as its proxy for lowering cholesterol and triglycerides. The authors of this definitive paper, the first of its kind to elucidate the cholesterol-vitamin D connection, claim vitamin D supplementation fails to improve cardiovascular outcomes, despite improving Cholesterol, LDL, and triglyceride numbers. 10 If it became widely known that vitamin D may be as good or better than statins (not hard to do), billions would be lost by pharmaceutical companies. Also, vitamin D is cheap and not patentable. So even if everyone ditched their drugs for the vitamin, the result is way less profit.
Here's the rub. Money in the form of scientific grants gets funneled into making more money. Promotion of statins based on their poor performance and crappy science makes money. By 2020, a trillion dollars had been spent on statins. 11 If you want research money, propose a new drug or support science that supports using the drug. If you design a study to debunk the usefulness of an existing drug or debunk the science on which its use is based, you won't get your grant. The result has been the creation of monolithic thinking in academia. If you don't think like your peers, you lose. Even if you complete a well-designed study that debunks pervasive groupthink, you will get peer-reviewed out of publication. Upton Sinclair once said, "It is difficult to get a man to understand something when his salary depends upon his not understanding it."
Here's what We Know
Science has gaps.
Research money comes with strings attached
Peer reviewers can have a bias
Statins lower cholesterol
Cholesterol is a poor predictor of heart disease
Lowering cholesterol has little effect on heart disease
Vitamin D lowers cholesterol
Vitamin D lowers inflammation
Oxidized cholesterol promotes heart disease
Vitamin D supplements should lower CoQ10, but it doesn't
Statins don't reduce vitamin D, and we don't know why
Any ability to reduce inflammation by statins is outweighed by the pain and damage they cause
Vitamin D reduces the side effects of statins
Statins only reduce death by less than one percent
Statin sales are in the billions
Money to prove vitamin D lowers heart disease is unavailable
Low vitamin D promotes heart disease