Untangling Cardiovascular Disease, Part 1
Can We Tame the Great Killer by Thinking Outside the Box?
This article is dedicated to my dear brother Jeff, may he rest in peace, taken from those who loved him at only 59 years old. Like a thief in the night, a heart attack robbed us of him. From this unbearable tragedy comes the motivation to research and write this series of articles. May the information I’ve spent the past months mining be the gems that can help you, and those you love.
The Worst Serial Killer Ever
We all know someone who died suddenly, ripped from our lives far too soon. Cardiovascular disease (CVD) often does precisely that—Killing quickly, without warning or mercy—The surviving family left traumatized by the abrupt loss and lack of closure. Sometimes referred to simply as heart disease (a name I’ll be avoiding in this article series), which can be a confusing term because myocarditis and cardiomyopathy can occur in the absence of vascular disease.
A systemic condition of blood vessels throughout the body, CVD is the leading cause of death around the world and here in the US, where it takes someone’s life every 34 seconds of every day. CVD has been on an unrelenting killing spree, responsible for a massive global burden of mortality and disability—more than 20 million people were wiped from existence in 2021—So the information in this series pertains to us all.
Many common factors increase the risk of vascular diseases, including smoking, high blood pressure, high cholesterol, diabetes, obesity, genetics, a sedentary lifestyle, diet, stress, and infections, with the most obvious one on the forefront of public consciousness being Covid. So most of the risk factors for heart disease are modifiable through lifestyle, medicines, and supplements. And as for changing our genes, for better or for worse, we’re getting there.
Cardiovascular disease causes a litany of ubiquitous miserable outcomes, including heart attack, stroke, heart failure, clots in the legs that travel to the lungs, and kidney failure—Any of which can lead to disability, reduced quality of life, and premature death.
There are some non-pharmaceutical remedies which have such abundant medical data supporting their use, that I’m continually shocked that cardiologists and general docs alike are not screaming about them from the rooftops. And then I remember that big pharma leads healthcare around like a puppy dog—So I guess, not so shocked.
But before jumping into this information, I want to emphasize that half a plan is a recipe for failure. No medication or supplement is a reliable remedy in isolation. So if folks were to think that they could continue with an unhealthy lifestyle, pop a few pills, and reduce risks for dire health consequences, I would kindly and with great empathy tell them what my father, may he rest in peace, said to me—To get their heads out of their collective asses. There’s simply no replacement for the 5 best doctors anyone can have—Dr. Diet, Dr. Sleep, Dr. Exercise, Dr. Happiness, and Dr. Sunshine.
And this series of articles doesn’t provide information on the importance of controlling cholesterol and blood pressure—Not because they’re not meaningful in mitigating cardiovascular disease—They are. But because you can get that information anywhere, from virtually any doctor. But in many cases it’s just not enough.
The intent of this series is to shine a light into the dark corners of cardiovascular disease—To expose the critical information that your doctors won’t tell you, simply because they don’t know.
And it should go without saying because it’s settled science, but I will say it anyway because I strongly believe it was a leading factor in my brother’s death—To smokers currently living in the hazy states of denial and addiction—Smoking and good cardiovascular outcomes are diametrically opposed. Every cigarette is an addictive poison, with marketing reprehensively targeted to “young adults,” an age group notorious for making terrible decisions.
There’s a scientific reason that teenagers do shockingly dumb things—The part of the brain that’s responsible for good decision-making doesn’t fully develop until the mid-late 20’s, so if people don’t get hooked on smoking before that, they likely never will. The following is an excerpt from a tobacco industry document:
"Younger adult smokers have been the critical factor in the growth and decline of every major brand and company over the last 50 years. They will continue to be just as important to brands/companies in the future for two simple reasons: The renewal of the market stems almost entirely from 18-
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year-old smokers. No more than 5 percent of smokers start after age 24…Younger adult smokers are the only source of replacement smokers... If younger adults turn away from smoking, the industry must decline, just as a population which does not give birth will eventually dwindle."
But that more mature adult smokers continue to smoke—That speaks both to the powers of addiction and denial. They should stop referring to denial as a “defense mechanism”—I think of it as a “self-destruct mechanism.”
I tried my best to get my brother Jeff to quit smoking, we all did, but nothing worked.
So without further ado, please join me on my train of thought, as I attempt to crack the code of cardiovascular disease.
Natto
A traditional Japanese food for over 1,000 years, natto is made from fermented soybeans. Although this Japanese breakfast staple is well-known for its health benefits, not everyone can stomach it. It’s unpalatable nature is almost the stuff of legend—If you weren’t fed natto as a kid, chances are you won’t be starting any time soon—Unless you can’t resist the smell of stinky socks with a splash of ammonia. And if that doesn’t draw you in, there’s its texture:
“But for many of us who didn’t grow up on natto, there is a certain yuck factor. Natto’s slimy coating — reminiscent of okra — led one biologist collaborator of Dr. Yonetani’s at Harvard, where she did research, to call it “Klingon food.””
Both stringy and slimy—Picture a boogie, but fermented—Then served up for breakfast. Then imagine that boogie tasting like earthy, funky, blue-cheesy, slightly bitter dirt.
That’s natto.
Gross, but Healthy
Natto is a nutrient-dense food, packed with protein, fiber, and vitamin B12, but that’s not what makes it special—Not even close. Particular to natto are some critical ingredients, two of which are vitamin K2-7 and nattokinase. Natto has the most vitamin K2-7 of any food source and is the only food source for nattokinase.
There are lots of epidemiologic studies looking at the relationship between natto consumption and health outcomes. Here’s some key research:
In a study of about 93,000 Japanese adults aged 45-74, intake of fermented soy products, such as natto and miso, were associated with a reduction in all cause mortality, with natto reducing cardiovascular diseases by 24% in men and 21% in women:
…in both men and women (hazard ratios for the highest fifths of intake were 0.76 (0.65 to 0.90, Ptrend=0.002) in men and 0.79 (0.65 to 0.95, Ptrend=0.01) in women…Natto intake was significantly associated with lower cardiovascular disease associated mortality in both men and women…Although both miso and natto are fermented soy products, only natto intake showed a significant reduction in cardiovascular disease related mortality in our study…”
In a study of about 29,000 people, those who ate the most natto, had 25% less deaths from any cardiovascular disease and 33% less deaths from clotting strokes in particular, compared to those who ate the least natto:
“The highest quartile of natto intake compared with the lowest intake was significantly associated with a decreased risk of mortality from total CVD after control for covariates: the HR was 0.75 (95% CI: 0.64, 0.88, P-trend = 0.0004). There were no significant associations between the risk of mortality from total CVD and intakes of total soy protein, total soy isoflavone, and soy protein or soy isoflavone from soy foods other than natto…The highest quartile of natto intake was also significantly associated with a decreased risk of mortality from ischemic stroke (HR = 0.67, 95% CI:0.47, 0.95, P-trend = 0.03).”
Importantly, the high natto consumption group did not experience an increase in hemorrhagic stroke, which is noteworthy because nattokinase has blood thinning effects. We have many anticoagulants in use, but each one carries a material risk of bleeding, sometimes life-threatening. Even the humble daily baby aspirin increases the risk of hemorrhagic stroke by 37% overall, with a whopping 84% increase among Asians. (Please make sure you read this entire article series because later on I review potential for bleeding risks for nattokinase too!)
A study of 944 post-menopausal women found improved bone health with eating natto:
“…natto intake and bone mineral density (BMD) and BMD change over time in healthy Japanese women…BMD was measured at the spine, hip, and forearm in 944 women (20-79 y old) at baseline and at a follow-up conducted 3 y later…total hip BMD at baseline increased (P for trend = 0.0034) with increasing habitual natto intake in the postmenopausal women…significant positive associations between natto intake and the rates of changes in BMD at the femoral neck (P < 0.0001) and at the distal third of the radius (P = 0.0002) in the postmenopausal women…No significant association was observed between the intake of tofu or other soybean products and the rate of BMD change in the postmenopausal women. Natto intake may help prevent postmenopausal bone loss…”
Many women take calcium for bone health on the advice of their doctors, but in my experience, almost none are being told that doing so may increase their risks for coronary artery disease. On the other hand, natto consumption may reduce risks for both bone loss and cardiovascular disease, but I’ve yet to encounter a patient who’s primary care doc has ever mentioned the word natto, let alone discussed its active constituents as a more palatable option than natto itself.
In a study of over 41,000 people, natto consumption was associated with a reduced dementia risk in women, whereas the consumption of other soy products was not:
“Although total soy product intake was not associated with disabling dementia risk, natto intake may contribute to reducing the risk of disabling dementia in women, especially in those aged under 60 years.”
Is this finding because of natto’s benefit to vascular disease (some dementias are caused by blood vessel damage)? Or is it due to another mechanism as well? I’ll explore this later on~
What We Don’t Know Can Kill Us
In medical school, I was taught that vitamin K is important for blood clotting—And that’s pretty much it. If you didn’t have enough vitamin K, you couldn’t clot—Which is why coumadin, also known as warfarin, works as an anticoagulant, because it blocks the actions of vitamin K.
It turns out that “vitamin K” is much more than what was taught to me in med school—It actually represents a group of fat-soluble vitamins, with overlapping but somewhat diverse properties. And they’re vitally important to not only cardiovascular and bone health, but also to myriad other areas. Vitamin K is broadly categorized into vitamins K1, annoyingly known by three different names: phylloquinone, phytomenadione, or phytonadione, and K2, also known as menaquinone. And nothing against vitamin K1, but K2 is by far the more captivating of the two. Whereas vitamin K1 stays primarily in the liver, Vitamin K2 is found more in tissues outside the liver.
To further complicate matters, vitamin K2 isn’t just one menaquinone—It’s a group of them with different chemical structures, each starting with the abbreviation “MK.” But for the purpose of this article series, I’m going to focus primarily on the two which are best studied, vitamin K2-4 (MK-4) and vitamin K2-7 (MK-7).
Of the menaquinones, MK-7, is the most well-studied of the longer chain versions. It’s well-absorbed and beneficial to the health of our blood vessels, bones, and nervous system, but MK-4, a short chain menaquinone, is no slouch. We convert vitamin K1 to MK-4 in our bodies, but how efficiently this occurs is not clear, and appears to differ according to tissue type. Most of our understanding of this conversion process comes from animal models—For example, in mice, all dietary forms of vitamin K are converted to MK-4—But is this the case in humans as well?
And yes, what I learned in medical school is correct—The vitamin K group is critical to blood clotting—Yawn. But here’s a cool factoid related to that boring piece of information—Although vitamin K deficiencies cause bleeding, higher intake doesn’t cause excess clotting:
“Abnormal clotting is not related to excessive vitamin K intake…”
Good to know.
And matrix GLA protein (MGP) is something we should also all know about because it functions as a soft-tissue calcification-inhibitor. Mice genetically lacking MGP die within about 2 months due to widespread arterial calcification. But MGP has to be in its activated form to be protective—Circulating levels of inactive MGP are associated with higher levels of vascular calcification, which is well-demonstrated in patients with chronic kidney disease and type 2 diabetes, two groups at risk for accelerated CVD. And simply stated, vitamin K-2 activates MGP, keeping calcium in the bones and out of soft tissues, like blood vessels.
What they didn’t know back when I was in med school was that coumadin, the above-mentioned blood thinner, by preventing vitamin K from activating MGP, not only causes increased bone loss—Even to the extent of osteoporosis—But that it also causes vascular disease. So even though coumadin keeps the blood thin, by preventing vitamin K from activating MGP, it does so while rusting the proverbial pipes.
Impact of Dietary Menaquinones (Vitamin K-2’s)
In this study, they followed 4807 people, analyzing their dietary intake of menaquinones, dividing them up into 3 groups: Lowest, middle, and highest intake. The high menaquinone group had a 57% reduction in cardiovascular mortality, a 26% reduction in all-cause mortality, and a 52% reduction in severe aortic calcification compared to the low menaquinone group. Notably, vitamin K1 intake was not related to any of these outcomes:
“The relative risk (RR) of CHD [coronary heart disease] mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes.”
For me, reading this study was an aha moment. It’s hard enough to argue with 4807 people, and harder still to argue with a 57% reduction in cardiovascular mortality. Noteworthy, was that this study was from The Netherlands, where natto isn’t traditionally consumed. So I looked for other similar studies from the land of wooden shoes.
Another study from The Netherlands found not only a reduction of CVD risk with vitamin K2 intake, but also a dose response curve, with further reductions of CVD risk with incrementally higher K2 intake. And notably, again, it didn’t find a reduction of CVD risk with vitamin K1 intake:
“After adjustment for traditional risk factors and dietary factors, we observed an inverse association between vitamin K(2) and risk of CHD [coronary heart disease] with a Hazard Ratio (HR) of 0.91 [95% CI 0.85-1.00] per 10 microg/d vitamin K(2) intake. This association was mainly due to vitamin K(2) subtypes MK-7, MK-8 and MK-9. Vitamin K(1) intake was not significantly related to CHD…Conclusions: A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD…
The richest source of menaquinones in the Western diet, inclusive of the EU, is from cheese. The French paradox, a low rate of CVD despite a diet high in saturated fats, is thought to be due to cheese consumption, which is associated with lower rates of CVD and type 2 diabetes. Cheeses are richer in MK-8 and MK-9 than MK-7. Even though MK-8 and MK-9 are not yet well-studied menaquinones, their presence in cheese may be meaningful—So the word of the day is Gouda, a Dutch cheese high in MK-8 and MK-9. (Ironically, I’ve referred to myself as being dense like Gouda in the past.)
And a third study from The Netherlands found that over 12 years, higher dietary intake of menaquinones, but again, not vitamin K1, was associated with a reduction of peripheral artery disease:
“Menaquinones intake was associated with a reduced risk of PAD [peripheral artery disease] with a hazard ratio (HR) of 0.71, 95% CI; 0.53-0.95 for the highest versus lowest quartile. A stronger association was observed (p interaction 0.0001) in participants with hypertension (HRQ4 versus Q1 0.59; 95% CI 0.39-0.87) or diabetes (HRQ4 versus Q1 0.56; 95% CI 0.18-1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk.”
The thing that jumped out at me from all three of these studies was that dietary intake of vitamin K1 was not associated with CVD mortality, peripheral artery disease, or aortic calcification. And yet…
Please join me in part 2 of Untangling Cardiovascular Disease, set to be released soon. As I meander down this path of discovery, my hope is that you and those you love can benefit from these revelations as they unfold.
Thank you for taking the time to consider my thoughts. I so appreciate your subscription to this newsletter (and am extraordinarily appreciative of those generously opting for the paid subscriptions!!). If you like what you’ve read here today, please opt for a full-access subscription and share ZeroSpin with people you care about.
Disclaimer: None of my posts, articles, podcasts, or any public communications contain medical advice. These are intended for purely informational purposes only. Please check with your doctor before undertaking any course of treatment.
Amazing first listen, yet too late at night! A second listen with coffee, on its way. Wow....such great research and findings...i am sure i speak on behalf of many, we can not thank you enough sir, for your passion and to help make our lives better and those we love...out of your own family tragedy, the power of the words on these pages....
You truly are an explorer...and a caring one at that.
New video on flccc.net on, guess what, Nattokinaise
Peter McCullough has been talking about it for a few months.
https://covid19criticalcare.com/tools-and-guides/all-about-nattokinase/
Much more information on this substack