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Posted by: | Posted on: December 8, 2025

Calcium Supplements and Dementia — Major Study Busts Long-Held Myth


Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/12/03/calcium-supplements-and-dementia-risk.aspx
Analysis by Dr. Joseph Mercola     December 03, 2025

calcium supplements and dementia risk

Story at-a-glance

  • Calcium supplements were long feared to increase dementia risk, but new long-term research found no connection between calcium use and cognitive decline, even among women with heart disease or prior strokes
  • The 14.5-year study published in The Lancet Regional Health showed that calcium carbonate supplements did not raise dementia-related hospitalizations or deaths, dispelling decades of concern about vascular calcification or brain damage
  • Your brain and bones rely on nutrient synergy — calcium works best when paired with magnesium, vitamin D3, and vitamin K2, which ensure calcium strengthens bones instead of depositing in arteries or soft tissue
  • Keeping your calcium-to-phosphorus ratio near 1:1 is key for both skeletal and cognitive health, since excessive phosphorus from processed foods, soda and meat-heavy diets forces calcium out of bones and contributes to arterial calcification
  • The safest way to protect your brain and bones is through whole-food calcium sources such as raw grass fed cheese, yogurt, and eggshell powder, paired with balanced sun exposure and nutrient cofactors that keep calcium working where it should

For decades, older adults have been warned that taking calcium supplements could harm their brains. Those warnings stemmed from small observational studies suggesting calcium might increase dementia risk by promoting vascular calcification or white matter lesions in the brain. Dementia, meaning a progressive decline in memory, reasoning, and behavior that interferes with daily life, affects 57 million people worldwide, according to the World Health Organization.1

It’s a devastating condition that robs independence, identity, and connection — so it’s no surprise that any hint of increased risk sparks concern. Calcium, however, is not a nutrient you can simply eliminate. It’s the most abundant mineral in your body and foundational for bone density, heart rhythm, muscle contraction, and nerve signaling. You need enough of it every day, especially as you age.

Yet the debate over how to get it — through diet or supplements — has persisted for years. Some experts argued that supplementing calcium floods your bloodstream and triggers calcium deposits in blood vessels, leading to stroke or cognitive decline. Others maintained that the risk was overstated and lacked solid evidence.

That’s why researchers from the University of Western Australia and colleagues conducted one of the most comprehensive long-term studies to date to determine whether calcium carbonate supplements truly raised dementia risk.2 What they found directly challenges years of fear-driven headlines and changes how you might think about calcium and brain health.

Long-Term Calcium Supplement Use Found Safe for Brain Health

The post-hoc analysis published in The Lancet Regional Health investigated whether taking calcium carbonate supplements increased dementia risk in older women.3 Researchers followed 1,460 women aged 70 and older who were dementia-free at the start of the study.

Half took 1,200 milligrams (mg) of calcium carbonate daily for five years, while the other half received a placebo. After an additional 9.5 years of follow-up, the researchers found no difference in dementia-related hospitalizations or deaths between the two groups.

• Older women were the focus because they face the highest risk of both osteoporosis and dementia — Calcium supplementation has long been prescribed to help offset accelerated bone loss in aging women.

However, past observational studies raised fears that supplements could promote calcium buildup in arteries and the brain. To address these concerns, researchers used hospital and death records to track dementia outcomes, providing a rigorous evaluation of calcium’s long-term neurological safety.

• The results showed no increased risk of dementia, hospitalizations, or deaths — Over the study period, 18.4% of participants experienced dementia events — 16.6% were hospitalized for dementia, and 7.8% died from dementia-related causes.

However, the difference between calcium and placebo groups was statistically insignificant. Calcium users had slightly lower — but not significantly different — rates of dementia compared to the placebo group. This finding held true even after adjusting for genetic, cardiovascular, and lifestyle risk factors.

• The researchers also found no effect from how well participants followed their supplement plan — Even among those who took 80% or more of their assigned tablets, known as the per-protocol group, calcium had no adverse effects on cognitive outcomes.

Compliance was similar between groups — about 57% overall — and those who adhered more closely to the treatment had a 27% lower relative risk of dementia, regardless of whether they were in the calcium or placebo group. This suggests healthier behavior patterns, not calcium intake itself, could explain differences in dementia outcomes.

Calcium’s Suspected Link to Dementia Was Largely Theoretical — and This Study Disproved It

Critics had speculated that calcium supplements could cause “intracellular calcium overload,” leading to cell death or calcified deposits in brain tissue. Others feared sudden spikes in blood calcium could damage blood vessel linings. However, no such effects were observed in this long-term controlled study. Researchers found no increase in carotid artery plaque or arterial wall thickening — two markers of vascular calcification — among supplement users.

• The study also addressed previous contradictory research — Two earlier observational studies claimed calcium users had up to six times higher dementia risk, particularly among women with a history of stroke or brain lesions.4,5

However, those studies were small and relied on self-reported supplement use rather than controlled dosages. By contrast, this randomized controlled trial provided calcium directly to participants and tracked adherence, eliminating much of the recall bias and confounding that weaken observational data.

• Even women with heart disease showed no increased dementia risk — Some researchers theorized that calcium supplements could worsen vascular problems or lead to calcification in the arteries, which could reduce blood flow to the brain.

Yet, when researchers separated women with existing atherosclerotic vascular disease from those without, results were the same — no association between calcium supplementation and dementia. The same held true for those with prior strokes or other cardiovascular issues.

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Synergistic Nutrients Strengthen Both Brain and Bone Health

Calcium’s behavior inside your body depends on a precise balance with other nutrients that determine where it goes and how it’s used. When that balance is right, calcium strengthens your bones and supports clear thinking. When it’s off, the same mineral can contribute to stiffness, fatigue, or vascular buildup. Understanding this synergy is the key to unlocking calcium’s full benefits for both brain and body health.

• Cognitive and skeletal health depend on nutrient teamwork, not single nutrients — Your brain and bones rely on a delicate balance of minerals and vitamins that work together — especially calcium, magnesium, vitamin D3, and vitamin K2.

Each plays a distinct role, but it’s their combined action that determines how effectively your body absorbs, uses, and stores calcium for long-term health. When these nutrients fall out of balance, calcium could end up in soft tissues like arteries instead of bones, where it’s needed most.

• Vitamin D3 directs calcium to where it belongs — Often called the “sunshine vitamin,” vitamin D3 helps your intestines absorb calcium efficiently and ensures it’s delivered into your bloodstream for proper use. Without adequate vitamin D3, your body struggles to maintain calcium balance.

This imbalance triggers a rise in parathyroid hormone (PTH), which pulls calcium from your bones to maintain blood levels, weakening skeletal strength and disrupting normal cellular processes that influence cognition. Sunlight exposure plays a central role in calcium regulation and brain health. Your skin produces vitamin D3 when exposed to sunlight, setting off a chain reaction that impacts both bone and brain function.

Proper vitamin D levels help regulate neurotransmitters, support mitochondrial activity, and protect against cognitive decline as you age. A lack of sunlight, on the other hand, makes even a calcium-rich diet less effective because your body can’t absorb or use the mineral properly without D3’s guidance.

• Magnesium keeps calcium in check and prevents harmful buildup — Acting as nature’s regulator, magnesium ensures calcium moves into bones and teeth instead of soft tissues. When magnesium levels are low, calcium often deposits in arteries, contributing to vascular calcification — a process associated with memory problems and cardiovascular disease. Balanced magnesium intake stabilizes this system, improving both vascular function and the nutrient delivery that fuels brain cells.

• Vitamin K2 activates proteins that lock calcium into your bone matrix — Found in fermented foods such as natto, sauerkraut, and aged cheeses like Gouda, Brie, and Edam, vitamin K2 turns on osteocalcin and matrix Gla-protein — two key compounds that guide calcium into bones and away from arteries. This mechanism reduces arterial stiffness, strengthens bone density, and supports the nutrient flow your brain depends on for healthy circulation and oxygen delivery.

• The four nutrients operate as a unified network that protects cognition — Calcium builds structural integrity; magnesium controls distribution; vitamin D3 governs absorption; and vitamin K2 ensures proper deposition. When one piece of this puzzle is missing, the system falters.

For example, supplementing calcium without magnesium or D3 could cause imbalances that increase calcification risk, while taking D3 without K2 could direct calcium into soft tissue rather than bone. The goal is harmony, not excess.

The Calcium-Magnesium Balance — Why Both Minerals Matter

Optimal bone health depends on maintaining balance between calcium and magnesium, a mineral that quietly governs calcium’s every move. While conventional advice has long prioritized calcium supplementation, the ratio between these two minerals is just as important as their total amounts.

• Both nutrients are widely underconsumed — Roughly 3.5 billion people worldwide risk inadequate calcium intake, mostly in low- and middle-income countries.6 At the same time, an estimated 45% to 60% of adults in developed nations fail to meet magnesium requirements through diet alone.7 Because only about 1% of magnesium is found in blood, routine lab tests often appear normal even when tissue levels are deficient, masking early imbalance.8

• The ratio matters as much as the amount — Studies suggest a calcium-to-magnesium ratio of about 2-to-1 (ranging from 1.7-to-1 to 2.6-to-1) may be ideal for metabolic and cardiovascular health, but the appropriate amount depends on magnesium form, diet quality, kidney function, and individual needs.9

Modern diets often reach calcium-to-magnesium ratios of 3-to-1 or higher, which limits magnesium absorption and promotes calcium buildup in soft tissue. Ratios exceeding 2.8-to-1 have been linked with inflammation, arterial stiffness, and metabolic stress.10

Keep in mind that these ratios refer to elemental magnesium, not the weight of the magnesium compound itself. Different forms of magnesium supply different amounts of elemental magnesium, and each type has specific characteristics. For example, systemic balance typically relies on forms like glycinate, citrate, or malate, while magnesium L-threonate supports brain magnesium levels at much lower elemental doses.

For this reason, magnesium needs cannot always be compared by compound weight alone, and intake should be assessed based on total elemental magnesium from both food and supplements, and supplemental forms are best chosen based on your personal health goals and tolerance.

• A balanced approach works best — Aim for whole-food calcium sources such as raw grass-fed dairy, leafy greens, powdered eggshell, small fish with edible bones, and algae-derived calcium. For magnesium, lean on legumes, dark leafy greens and, if needed, well-tolerated supplemental forms.

Both minerals act in concert — magnesium activates vitamin D, drives calcium into bone, supports hundreds of enzymatic reactions, and prevents inappropriate calcification, while calcium provides the structural framework for bones and muscles.

If supplementing, limit calcium to 500 mg per dose and select a formula that pairs both minerals in a 2-to-1 ratio. Think of calcium and magnesium as partners, not competitors — each depends on the other for optimal brain, bone, and cardiovascular health.

Keeping Calcium and Phosphorus in Balance Protects Your Brain and Bones

Your calcium-to-phosphorus ratio is another key player in how well your body maintains strong bones and clear thinking. Most people think of calcium as the key mineral for bone health, but phosphorus is equally important — and too much of it disrupts the entire system.

Calcium and phosphorus work in tandem to maintain bone density and nerve signaling, yet when phosphorus intake far exceeds calcium, your body compensates by pulling calcium out of bones to restore balance in your blood. This imbalance doesn’t just weaken your skeleton — it also stresses your cardiovascular and nervous systems, both of which influence brain health.

• Modern diets have tilted this ratio in the wrong direction — The ideal calcium-to-phosphorus ratio is between 1:1 and 1.3:1, meaning you should consume roughly equal amounts of each mineral. However, many people today are closer to 0.3:1 — three times more phosphorus than calcium.

This imbalance is fueled by excessive consumption of animal protein, processed foods, and grain-based products, all rich in phosphorus but low in calcium. When this ratio stays low for years, it accelerates bone loss, increases vascular calcification, and contributes to obesity and premature aging.

• Excess phosphorus forces calcium to leave your bones, triggering a cascade of problems — When phosphorus levels rise too high, your PTH increases to restore equilibrium. PTH does this by pulling calcium from bones into your bloodstream, keeping blood calcium stable but at the cost of bone strength.

Over time, this process erodes bone density, increases fracture risk, and contributes to osteoporosis — a condition marked by brittle bones and slow healing. The same process also promotes arterial stiffness and calcium buildup in soft tissues, increasing cardiovascular strain and reducing brain oxygenation.

• Phosphorus overload often comes from hidden sources — Processed meats, soda, energy drinks, and packaged snacks frequently contain phosphate additives that sharply elevate intake without providing the balancing minerals your body needs.

Even diets high in red meat skew the ratio toward excess phosphorus if calcium sources aren’t prioritized. Reading ingredient labels and minimizing processed foods are simple steps that protect both your bones and cognitive function.

• Managing your calcium-phosphorus ratio is straightforward once you know what to focus on.

◦Prioritize calcium-rich foods such as raw grass fed cheese and yogurt.

◦Limit processed meats, colas, and fast foods that contain phosphate preservatives.

◦Consider using natural food-based calcium sources such as raw grass fed dairy, small fish with bones, algae-derived calcium, or powdered eggshell. Each provides calcium in a form your body can use, and the right choice depends on your diet, preferences and tolerance.

◦Add a magnesium supplement to help regulate calcium transport and reduce vascular stress.

◦Get sunlight exposure to optimize your vitamin D levels and help your body use calcium efficiently and stabilize hormone balance.

The Best Calcium Sources Come from Food, Not Pills

When you understand how your body uses calcium, you start to see why whole foods work better than isolated supplements. Calcium doesn’t act alone — it relies on a network of nutrients, including magnesium, vitamin D3, and vitamin K2, to reach your bones instead of your arteries or brain.

It’s also balanced by phosphorus, another mineral that’s often too high in modern diets due to processed foods and excessive animal protein. Restoring that mineral harmony keeps your bones strong, your arteries clear, and your mind sharp as you age.

1. Start with food-based calcium every day — You’ll absorb calcium best from whole foods that naturally contain the right mineral balance. Include raw grass fed cheese, Greek yogurt, cottage cheese, and cooked collard greens — if your gut tolerates them — regularly.

These foods provide bioavailable calcium that your body recognizes and puts to work immediately. They also deliver trace minerals and natural fats that support hormone balance and nutrient absorption — two key elements of long-term bone and brain health.

2. Powdered eggshell provides a pure, natural calcium boost — Powdered eggshell is made mostly of calcium carbonate — the same compound found in your bones — and contains 27 other trace minerals that improve calcium uptake. Take about 1/2 teaspoon of eggshell powder three times a day with meals to provide roughly 1,300 mg of calcium.

I recommend mixing it into smoothies, yogurt, or soups. It’s inexpensive, effective, and free of contaminants that often plague bone meal products. If you notice any constipation, consider taking magnesium alongside the eggshell calcium for better results.

3. Pair calcium with magnesium, vitamin D3, and vitamin K2 — Calcium and magnesium work like teammates — one tightens muscles and nerves, the other relaxes them. Without enough magnesium, calcium builds up in soft tissues instead of strengthening bones.

Vitamin D3 and vitamin K2 complete the team: D3 helps you absorb calcium efficiently, while K2 activates proteins that guide it into your bone matrix and keep it out of arteries. This trio — magnesium, D3, and K2 — ensures calcium goes exactly where it should, supporting steady energy, vascular health, and sharper cognition.

While leafy greens provide excellent dietary magnesium, due to depleted soils many healthy foods have lower levels of nutrients than they used to. As a result, many people still need supplementation to reach optimal magnesium levels. Generally, your magnesium intake should be about half of your calcium intake — so if you’re consuming 1,000 mg of calcium, your ideal magnesium intake is about 500 mg.

When taking magnesium, start with magnesium citrate, which is absorbed well but will cause loose stools if you take too much. Gradually increase your dose until that happens, then back off slightly. That’s your personal threshold. Once you know it, switch to forms like magnesium glycinate, malate, or threonate, which deliver the benefits without upsetting your digestion.

To optimize your vitamin D levels, aim for sun exposure on bare skin daily, without sunscreen, but avoid exposure during peak hours (10 a.m. to 4 p.m.) until you’ve eliminated seed oils for at least six months to reduce sun sensitivity. Test your vitamin D levels regularly and aim for 60 to 80 ng/mL (150 to 200 nmol/L).

4. Balance your calcium-to-phosphorus ratio for bone and brain protection — Most people consume far more phosphorus than calcium, which forces your body to pull calcium from your bones to restore balance in your blood. Over time, this weakens bones and promotes calcium deposits in arteries.

To correct this, reduce processed foods, colas, and grain-heavy meals, and increase calcium-rich options such as raw grass fed dairy, eggshell powder, and cooked greens. Aim for a calcium-to-phosphorus ratio close to 1:1 by combining calcium-rich foods with moderate protein intake. This keeps both your skeleton and your cardiovascular system in harmony.

5. Use calcium strategically — not excessively — More isn’t always better. Most adults need around 1,000 to 1,300 milligrams of calcium per day from all sources combined, balanced with magnesium, vitamin D and K2. Avoid overdoing protein or processed foods that drive up phosphorus, and remember that consistent, balanced intake — not high doses — creates the real results.

Most adults need about 0.8 grams of protein per pound of ideal body weight (the weight you would ideally be, not necessarily the weight you are now), or for Europeans, approximately 1.76 grams of protein per kilogram. Ideally, get roughly one-third of your protein from collagen sources like bone broth or grass fed ground beef, which contains connective tissue, or glycine to support connective tissue health.

Balanced nutrition supports strong bones, clear arteries, steady energy, and cognitive resilience throughout your life. By shifting toward whole food sources and respecting your body’s mineral rhythms, you give yourself the best chance to maintain both skeletal and cognitive health for decades to come.

FAQs About Calcium, Brain Health, and Cognitive Resilience

Q: Does taking calcium supplements increase your risk of dementia?

A: No. According to research published in The Lancet Regional Health, calcium carbonate supplements did not increase the risk of dementia, hospitalizations, or dementia-related deaths in older women who took them for five years and were followed for 9.5 years afterward.11 The findings showed no link between calcium supplementation and vascular calcification or cognitive decline.

Q: How do vitamin D3, magnesium, and vitamin K2 work with calcium to protect your brain?

A: These nutrients act as a coordinated team. Vitamin D3 helps your intestines absorb calcium and directs it into your bloodstream; magnesium regulates calcium’s movement so it enters your bones instead of your arteries; and vitamin K2 activates proteins that “lock” calcium into bone tissue. Together, they ensure calcium supports bone strength and brain health without causing harmful deposits in soft tissues.

Q: Why is the calcium-to-phosphorus ratio important for cognitive and bone health?

A: An ideal calcium-to-phosphorus ratio of about 1:1 maintains balance between bone-building and cellular energy processes. Most modern diets deliver three times more phosphorus than calcium due to high intake of animal protein, processed foods, and soda. This imbalance causes calcium to leach from bones, weakens skeletal structure, and promotes calcium buildup in arteries — raising the risk of cardiovascular and cognitive problems.

Q: What are the best food sources of calcium and its supporting nutrients?

A: Whole, minimally processed foods are your best option. Raw grass fed cheese, Greek yogurt, cottage cheese, and cooked leafy greens provide highly absorbable calcium. For magnesium, focus on cooked greens, potatoes, and bananas, but most people need supplementation to support their levels. Vitamin D3 is produced naturally from sunlight exposure, and vitamin K2 is found in fermented foods like natto, sauerkraut, and aged cheeses such as Gouda or Brie.

Q: How can you safely optimize your calcium intake for brain and bone health?

A: Rely primarily on food-based calcium. Raw grass-fed dairy, small fish with bones, algae-derived calcium, and powdered eggshell all supply the mineral in natural forms that work well with your biology. Choose the source that best supports your digestion and overall nutrient intake.

Pair calcium with magnesium, vitamin D3, and vitamin K2 to ensure proper absorption and placement in your body. Avoid overconsuming phosphorus-rich or processed foods, and aim for daily sunlight to maintain ideal vitamin D3 levels. Consistency — not high doses — is what sustains strong bones, clear arteries, and lasting cognitive vitality.

 

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Posted by: | Posted on: July 9, 2025

The Crucial Connection Between Vitamin K2, Calcium Metabolism, and Disease Prevention


Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/07/06/vitamin-k2-calcium-metabolism-disease-prevention.aspx

Analysis by Dr. Joseph Mercola     July 06, 2025

Story at-a-glance

  • Vitamin K2 directs calcium into your bones instead of arteries, which helps keep them strong and reduces calcification that leads to heart disease
  • A Nutrients review revealed that higher K2 intake improved bone mineral density (BMD) and slashed fracture risk, particularly among older adults and postmenopausal women
  • Your apolipoprotein E (ApoE) genotype influences how your body processes vitamin K2. ApoE 2/2 individuals clear it slowly, risking buildup, while ApoE 3/4 or 4/4 clear it fast, requiring higher doses
  • MK-4, found in animal foods, has a short half-life; MK-7, from natto or supplements, lasts longer. Matching the correct form to your genetic profile helps ensure optimal calcium transport
  • To direct calcium where it belongs, balance vitamin K2 with D3, avoid vegetable oils, and get enough magnesium. This will help prevent arterial calcification while maintaining strong bones and reducing your fracture risk

For decades, the conventional advice for optimal bone health has been to take calcium supplements — but the fact is that without the right co-factors, like vitamin K2, this nutrient doesn’t end up strengthening bones, and could cause damage instead.

Vitamin K2 ensures that calcium binds to bone where it belongs. Without sufficient amounts of K2, calcium builds up in places where it shouldn’t — like your arteries — while leaving your bones weak and brittle. This is why people with low vitamin K2 levels often develop both osteoporosis and hardened arteries, a paradox that drastically increases their risk of fractures and heart disease.

Vitamin K2 Strengthens Bones and Protects Against Fractures

A review published in Nutrients examined the role of vitamin K2 in bone health, specifically its impact on bone mineral density (BMD) and fracture risk in adults. The researchers focused on how K2 influences calcium utilization in the body, ensuring that this essential mineral strengthens bones rather than accumulating in arteries.1

• Vitamin K2 strengthens skeletal function — The study analyzed a population of older adults, who are particularly vulnerable to bone loss and fractures. They found that participants who regularly consumed vitamin K2, whether through diet or supplementation, exhibited stronger bones and a lower risk of fractures compared to those with lower intake levels.

The researchers noted that K2 supplementation was especially beneficial for postmenopausal women, who are at the highest risk for osteoporosis-related fractures.

• Bone mineral density is higher — One of the most striking findings was the measurable increase in BMD among those supplementing with K2. Bone density improved significantly within months, reducing the likelihood of fractures over time. Individuals with low K2 intake had signs of weakened bone structure, making them more susceptible to breaks from minor falls or injuries.

• Risk of fractures is reduced — The study also looked at fracture rates over time. Participants with higher K2 intake had fewer fractures, particularly in the hip and spine, two of the most vulnerable areas in aging individuals.

The difference was significant — those with insufficient K2 intake experienced nearly twice as many fractures as those who maintained adequate levels. This suggests that K2 not only improves bone density but also enhances bone strength and resilience.

• Vitamin K2 directs calcium — The biological mechanism behind these findings is straightforward but powerful. Vitamin K2 activates key proteins — osteocalcin and matrix Gla protein (MGP) — which direct calcium where it is needed and prevent it from accumulating where it shouldn’t.

Osteocalcin ensures calcium binds to the bone matrix, while MGP prevents calcium deposits from forming in arteries. Without sufficient K2, these proteins remain inactive, leading to both weakened bones and arterial calcification.

• Vitamin D interplays with vitamin K2 — To summarize, the researchers said, “[W]e find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed.”2

Concerns and Challenges Regarding Vitamin K2 Absorption

However, there are significant challenges when it comes to optimizing vitamin K2. For example, testing isn’t widely available, as most doctors do not consider it part of routine health screenings. There are also individual factors that affect your ability to utilize K2, one of which is your genetics.

• The journey to testing vitamin K2 — In the video above, Nadir Shah, a licensed structural engineer and educational consultant who runs the YouTube channel “Knowledge for Quality of Life,” shares his personal health journey and how he discovered that your genetic makeup influences the amount of vitamin K2 you absorb.

His research began back in 2021, when he and his wife (who has osteopenia, or bone density loss) became curious if they are meeting the optimal levels of nutrients — particularly for vitamin K2.3

• Vitamin K2 testing is challenging — According to Shah, “There is no such test that which can test all the micronutrients and all the vitamins, all the minerals, because I’ve been hunting those tests, basically in the insurance literature, health insurance, which I’m covered with, and there’s none basically.

We’ve been taking vitamin K2 along with vitamin D, which I have mentioned in my previous vlogs. We’ve been taking 100 micrograms, myself and my wife, both. We’ve been taking the same dosage. But there is no test for vitamin K2,” Shah explained.4

After an extensive search, Shah was able to find two labs that offered testing for K2 — Genova Diagnostic and Vibrant Labs of America. However, there is no separate K2 test; it’s actually part of a micronutrient panel test that costs nearly $400. What’s more, the test needs to be prescribed by a physician.5

• Finding a solution — According to Shah, he found an integrative medicine doctor in Phoenix, Arizona who recommend Vibrant Labs of America for micronutrient panel testing. After this encounter, his family got their results after four to six weeks.

• The importance of getting tested — Shah noted that, “[T]he eye-opening thing for me in that test … was the vitamin K2 level. I came OK in vitamin K2, but my wife was a bit short. She was OK at the serum level, when I say serum level means it’s the blood level, but at the blood cells at the cellular level, she falls short. And that was an alarming point for me …”

As Shah and his wife were taking the same dose, he then sought answers as to why there was such a significant difference in their levels. Her cellular levels of this nutrient were not reaching the optimal amount, which means it’s not activating the vitamin K-dependent proteins, matrix GLA protein and osteocalcin. It took him months, but he eventually found the answer in a research paper.6

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The Role of ApoE Genotype in Vitamin K2 Absorption

Your apolipoprotein E (ApoE) genotype is one of the key genetic markers involved in processing vitamin K2. This gene influences how your body processes fats and vitamins, including vitamin K2. There are different variations of the ApoE gene, and depending on which one you inherit, your body may either clear vitamin K2 quickly or retain it for a longer time. In Shah’s case, he and his wife have different ApoE genotypes.7

• The differences in genotypes — According to Shah, “There are genotypes which we have inherited from mom and dad. There are basically three copies: 2, 3, and 4. Then there is a combo 2/3, 3/3, 3/4, and 4/4. So, there’s a combination of six altogether. These are called ApoE genotype alleles.”

• Genotypes determine vitamin K2 clearing — Shah continues, “I found out in that paper that people who are ApoE 2/2, they clear vitamin K2 very slow; particularly, their clearance rate is very slow. Now, 3/3 are typically neither slow nor fast, but 3/4 and 4/4 people — people who carry ApoE one copy of 4 or double copy of 4 — they clear their vitamin K2 from the body pretty fast.

It means that the dosage which I’ve been taking, 100 micrograms … was okay because I’m 3/3. We got both tested after that and that was like a light bulb went on,” Shah says.8

Many people do not know their ApoE genotype because it is not a standard diagnostic test. However, getting tested provides valuable insights into how your body processes vitamin K2 and other nutrients. After learning this information, Shah increased his wife’s K2 dose, and since then they have seen noticeable results.

• The impact of increasing vitamin K2 intake — Shah recalls their story, “Since 2021, we did another DEXA scan. Her osteopenia stopped progressing at two locations. That’s a good sign. Very good sign. Because if … the T-score doesn’t go in the negative further, it means that it has stopped. It means that she is getting enough K2 …”

• Boosting your vitamin K2 intake has no side effects — According to Shah, his wife is “eating natto as well. She is in the range of probably 800, 900 micrograms — eight- or ninefold than what she was taking before. And I am the same way. I increased even though I was okay, but I increased because there is no, we don’t feel any side effect, nothing whatsoever.”9

He adds that understanding your ApoE genotype is also useful for other aspects of your health. Certain variations are linked to a higher risk of Alzheimer’s disease, cardiovascular issues, and how your body handles cholesterol. Knowing this information will help you make better choices about your diet, supplements, and overall lifestyle.

The Type of Vitamin K2 You Take Matters

Shah also mentions that the form of vitamin K2 affects how efficiently you absorb it. The most common forms are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).

• The difference between MK-4 and MK-7 — Shah explains, “MK-4’s half-life is only four hours and MK-7’s half-life is 72 hours. It stays in the system in the body longer … So, it means that MK-7 is not good for people who are ApoE genotype 2/2, because I’ve been seeing a lot of people when they take K2 MK-7, they feel palpitation.

What happens is that, based on the literature, if they take [it] on daily basis, the body is not clearing because it’s clearing slow, it’s going to back up and then it’s going to give you a side effect.”

• Your genotype dictates which form of vitamin K is better — From Shah’s findings, he noted that “People who are ApoE genotype 2/2, based on the literature, they are better off with MK-4 because it clears fast. Now, if you are 2/2 — the only way we are going to know what type of ApoE genotype we carry is we need to get tested, and it’s a once in a lifetime test.”10

• Top sources of MK-4 — MK-4 is a short-chain form of vitamin K2 found in animal products such as meat, eggs, liver, and dairy.11,12 However, it has a short biological half-life, which makes it a poor candidate as a dietary supplement. However, MK-4 from food is important for good health as it plays a role in gene expression. For example, research has found it helps lower your risk of liver cancer.13

• Top sources of MK-7 — Meanwhile, MK-7 is a longer-chained vitamin K2 found in fermented foods such as sauerkraut, certain cheeses, and natto. It’s produced by specific bacteria during the fermentation process. However, not all strains of bacteria make it, so not all fermented foods will provide it.14

How to Make Sure Calcium Goes to the Right Places

If you want strong bones and flexible arteries, getting enough vitamin K2 is non-negotiable. Without it, calcium ends up in all the wrong places — clogging your arteries instead of strengthening your bones. The good news is, you have control over this. By making a few simple adjustments, the calcium you ingest will work for you, not against you.

1. Get enough vitamin K2 from the right sources — Your body needs K2 to activate the proteins that direct calcium into your bones and keep it out of your arteries. The best natural sources are natto, hard cheeses like Gouda, egg yolks, and organ meats.

If you don’t regularly eat these foods, consider a high-quality vitamin K2 supplement. If you opt for an oral K2 supplement, it’s best taken with your evening meal, along with any vitamin D and/or calcium and magnesium you’re taking.

2. Balance your vitamins D3 and K2 intake — If you are supplementing with calcium and vitamin D3 but not vitamin K2, you’re making a huge mistake. Vitamin D3 increases calcium absorption, but, as discussed, you need K2 to prevent that extra calcium from going where it doesn’t belong.

Always make sure that for every 5,000 IUs of vitamin D3 you take, you’re also getting around 180 micrograms (mcg) of vitamin K2. This keeps calcium metabolism in balance and prevents calcification where you don’t want it.

3. Eliminate vegetable oils and processed foods — Too much linoleic acid (LA), found in vegetable oils like soybean, canola, and corn oil, damages your arteries, making them more vulnerable to calcium buildup.

Processed foods are packed with these inflammatory oils, so eliminating them from your diet is one of the best strategies to support your heart and overall health. Instead, cook with saturated fats like grass fed butter, ghee, or tallow, and avoid anything that lists vegetable oil as an ingredient.

4. Get more magnesium to keep calcium in check — Along with vitamin K2, magnesium is another key to proper calcium regulation. It helps prevent calcium from accumulating in soft tissues. If you’re not getting enough magnesium, your body struggles to properly use both vitamins K2 and D3.

The easiest way to find your ideal magnesium dose is by using magnesium citrate — slowly increasing the amount until you notice loose stools, then backing off slightly. Once you know your threshold, you can switch to other forms of magnesium, such as magnesium threonate (which doesn’t cause loose stools), for better brain and bone benefits.

If you’re eating a balanced diet with dairy, leafy greens, and bone broth, you probably don’t need extra calcium. Instead, focus on getting the right co-factors mentioned above, and let your body handle the rest naturally.

Frequently Asked Questions on Vitamin K2 and Bone Health

Q: Why is vitamin K2 important for bone health?

A: Vitamin K2 plays a crucial role in directing calcium to the bones, where it strengthens bone mineral density (BMD) and reduces fracture risk. Without sufficient K2, calcium accumulates in arteries instead, increasing the risk of both osteoporosis and cardiovascular disease.

Q: How does vitamin K2 impact bone density and fracture risk?

A: Studies show that vitamin K2 supplementation improves BMD and significantly reduces fractures, especially in older adults and postmenopausal women. It activates osteocalcin and matrix Gla protein (MGP), which ensure calcium binds to bones rather than accumulating in arteries.

Q: What factors affect vitamin K2 absorption in the body?

A: Genetics, specifically the ApoE genotype, influence how quickly your body clears vitamin K2. Individuals with ApoE 3/4 or 4/4 genotypes clear K2 faster and will need higher doses, while those with ApoE 2/2 clear it slowly and are better suited to the MK-4 form of vitamin K2.

Q: What are the best sources of vitamin K2?

A: Natural sources of vitamin K2 include fermented foods like natto, cheese made from grass fed dairy, egg yolks and organ meats. For supplementation, MK-4 has a shorter half-life and is better suited for fast K2 metabolizers, while MK-7 remains in the body longer and is preferable for slower metabolizers.

Q: How can I ensure calcium is used properly in my body?

A: To direct calcium to bones and prevent arterial calcification, maintain a balance of vitamins K2, D3, and magnesium. Aim for 180 mcg of vitamin K2 for every 5,000 IUs of D3. Also, avoid processed foods and vegetable oils, which contribute to arterial damage and improper calcium distribution.

Posted in Bones, Calcium, Vitamins | No Comments »

Posted by: | Posted on: July 3, 2025

Fisetin — An Unsung Hero in the Fight Against Vascular Calcification


Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/07/03/fisetin-cardiovascular-benefits.aspx

Analysis by Dr. Joseph Mercola     July 03, 2025

fisetin cardiovascular benefits

Story at-a-glance

  • Fisetin, naturally found in strawberries, apples, and onions, prevents artery stiffness by halting harmful calcium buildup in blood vessels
  • Regular consumption of fisetin-rich foods significantly reduces inflammation and oxidative stress, effectively lowering your risk of heart disease and stroke
  • Fisetin enhances your body’s natural defenses by activating enzymes that switch off dangerous signals responsible for arterial calcification
  • Eliminating ultraprocessed foods from your diet protects your arteries from chronic inflammation and metabolic damage
  • Daily physical activity and targeted carbohydrate intake help maintain healthy insulin levels, which is essential for preserving flexible arteries and good cardiovascular health

One of the most overlooked threats to your cardiovascular health is vascular calcification, meaning your arteries harden and stiffen as calcium builds up within their walls.

When your arteries lose flexibility, your heart works harder to pump blood, significantly raising your risk for hypertension, heart attack, and stroke. In fact, you could have it right now. Research indicates that nearly half of all adults over the age of 60 have some level of calcification throughout their body, also known as diffuse calcification.1

To manage the issue, researchers are turning towards fisetin, a natural flavonol found abundantly in foods like strawberries, apples, and onions. Interestingly, fisetin also exhibits antioxidant and anti-inflammatory properties that promote better overall health.

Fisetin Prevents Calcium Buildup in Arteries

In a study published in Aging,2 researchers investigated how fisetin helps prevent vascular calcification, a process that makes your blood vessels stiff and less able to function properly. To conduct their study, they used human vascular smooth muscle cells, segments of mouse arteries, and a special mouse model that mimics calcification caused by too much vitamin D.

The team treated cells and tissues with high levels of calcium and phosphate, which simulates conditions that promote artery hardening, and then added fisetin. They closely monitored changes in calcification markers, such as genes and proteins involved in calcium deposition.

• The impact of fisetin on cardiovascular health — When fisetin was added, it dramatically reduced the buildup of calcium in the artery cells and in artery segments from mice. Specifically, it lowered activity levels of genes known to promote calcification, including BMP2, ALPL, and CBFA1.

For context, BMP2 is a gene that signals your body to start depositing calcium, ALPL promotes mineralization, and CBFA1 is crucial in transforming smooth muscle cells into bone-like cells — none of which you want happening in your arteries. In other words, fisetin directly interrupts the dangerous transformation of your artery cells from smooth, flexible structures into hardened, calcium-filled tissues.

• Going deeper into fisetin’s effectiveness — The researchers observed that fisetin significantly reduced calcification markers across all experimental setups, proving it is consistently beneficial, and this wasn’t a minor improvement at all. It was substantial enough to suggest that regular intake of fisetin-rich foods or supplementation could effectively shield your arteries from harmful calcium buildup.

Interestingly, these benefits hinged strongly on one crucial enzyme called dual-specificity phosphatase 1 (DUSP1). When researchers turned it off, fisetin lost its protective effects completely. Even worse, shutting down this enzyme increased calcification, showing that DUSP1 is what fisetin activates to halt the hardening of arteries.

• Fisetin works right away — Time-related specifics were equally striking. In mouse models overloaded with vitamin D (a known way to rapidly induce artery calcification) the introduction of fisetin led to visible improvements in as little as two weeks. Calcium deposits were lower, showing fisetin works swiftly to prevent artery stiffening from progressing once introduced.

• Groups who will benefit the most from fisetin — The research strongly indicates that anyone already at risk from conditions like kidney disease, diabetes, or vitamin D overload (which excessively raises calcium levels) will likely see significant heart-health benefits from fisetin. These groups typically face higher risks of rapid vascular calcification.

Conversely, the effectiveness of fisetin compared to untreated scenarios was stark. Cells and tissues exposed to high phosphate and calcium without fisetin quickly became calcified, mirroring the conditions that lead to stiff, blocked arteries in people. But with fisetin treatment, those same tissues remained flexible and significantly less mineralized.

• A look into the biological processes — The central player in vascular calcification is a protein called p38 mitogen-activated protein kinase (p38 MAPK). Think of this protein as a harmful switch that, when activated by stress signals like excess calcium and phosphate, instructs your artery cells to harden and calcify.

Fisetin’s primary action involves activating DUSP1. When it raises the levels of DUSP1, p38 MAPK gets turned off, blocking the harmful signal pathway.

• Fisetin also helps maintain balance in cell signaling — Normally, cells in your arteries carefully regulate their internal calcium levels, but certain conditions disrupt this balance. High phosphate, chronic inflammation, and metabolic disorders upset calcium regulation, pushing smooth muscle cells toward calcification. By enhancing DUSP1 activity, fisetin restores balance, preserving the natural state of your arteries and safeguarding your cardiovascular system from unnecessary strain.

• The dual role of fisetin for your overall health — Not only does fisetin halt calcium buildup, it also addresses inflammation and oxidative stress, which are powerful contributors to artery disease.

Other Health Benefits of Increasing Fisetin Intake

In a meta-analysis published in Acta Scientific Nutritional Health,3 researchers investigated the different health-promoting effects of fisetin. Moreover, they highlighted its specific advantages for your cardiovascular system.

• Maintain lipid balance — This means your cholesterol and triglyceride levels become healthier. Animal studies showed substantial reductions in LDL cholesterol, commonly called “bad cholesterol,” and triglycerides after fisetin administration. This improvement is essential because lower LDL and triglycerides directly reduce your risk of plaque buildup in arteries, thereby dramatically lowering your chance of heart attack or stroke.

• Improve insulin sensitivity — This is a critical factor for managing and preventing Type 2 diabetes and its related cardiovascular complications. Laboratory tests showed improvements within weeks of fisetin supplementation, particularly on animal models of insulin resistance.

• Manage blood pressure — Several studies cited in the review demonstrated significant drops in blood pressure after fisetin was administered regularly. High blood pressure puts relentless strain on your heart and arteries, increasing risks of severe cardiac events.

• Control metabolic dysfunction — The most substantial cardiovascular benefits of fisetin appeared among test animal models. In these groups, fisetin not only normalized cholesterol levels and blood pressure, but also reduced inflammation. These benefits could also translate for human applications, too.

• Modulate the MAPK pathway — As noted in the previous study, this pathway triggers inflammatory responses in your blood vessels, contributing to plaque buildup and vascular damage if unchecked. Studies reviewed showed that fisetin blocks these inflammatory signals at their source, creating powerful protection against heart disease.

• Antioxidant capabilities — Antioxidants help neutralize harmful free radicals, and fisetin stands out because it specifically protects cardiovascular tissues. Previously published literature outlined in the featured study illustrated that fisetin directly scavenges damaging free radicals in heart cells, reducing oxidative stress and minimizing tissue damage.

When oxidative stress is controlled, your heart stays healthier and functions more effectively, significantly reducing your risks of long-term cardiovascular conditions.

• Anticancer properties — Interestingly, the researchers noted that fisetin helps fight cancer, specifically by activating tumor suppressor pathways through the p53 protein:4

“P53 is often referred to as the ‘guardian of the genome’ because it regulates critical cellular processes, such as DNA repair, cell cycle arrest, and apoptosis (programmed cell death), in response to cellular stress or DNA damage.

In many cancers, p53 is either mutated or downregulated, leading to uncontrolled cell growth and evasion of apoptosis. Fisetin has been shown to restore or enhance the function of p53, promoting cell cycle arrest and apoptosis in cancer cells.”

• Endothelial function support — Healthy endothelial cells are crucial for proper circulation, blood pressure control, and overall heart health, and fisetin was shown to help keep endothelial cells functioning optimally, maintaining healthy blood vessel dilation and smooth blood flow.

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How to Protect Your Arteries and Improve Cardiovascular Health

If you’re dealing with early signs of arterial stiffness or simply want to ensure your cardiovascular system remains strong, tackling the root causes is your best strategy. Here are my recommendations to help you effectively improve your heart health naturally:

1. Boost your fisetin intake through diet — Start incorporating more fisetin-rich foods into your meals daily. Strawberries, apples, onions, cucumbers, and even persimmons contain significant amounts of this beneficial flavonol. As the prior studies have shown, increasing your fisetin intake will help reduce the risk of artery calcification, as well as lower inflammation, and improve overall heart health.

2. Cut out ultraprocessed foods from your life — Avoiding ultraprocessed foods, especially those high in linoleic acid (LA) is one of the most effective steps to protect your cardiovascular system.

These synthetic products directly fuel inflammation and oxidative stress, which are major drivers of artery stiffness. Instead, replace these harmful choices with whole, nutritious foods. Ideally, swap high-LA vegetable oils with healthy fats instead, such as grass fed butter, ghee, or tallow.

For a detailed explanation of the dangers that LA poses to human health, I encourage you to read my study published in Advances in Redox Research.5 There, I discuss crucial topics, such as LA’s effect on cardiolipin, metabolic function, and gut microbiome.

3. Get moving with regular exercise — Make exercise a non-negotiable part of your routine. Whether it’s biking, swimming, or lifting weights, regular physical activity significantly reduces inflammation and insulin resistance, improving the flexibility and health of your arteries.

If you are new to exercise, I recommend you start walking. This simple act, done gradually and steadily, is one of the most effective forms of exercise anyone can do. Best of all, it’s an exercise that can’t be overdone. For an in-depth look at the benefits of walking, read “The Benefits of Walking — How to Get More Steps in This Summer.”

4. Lose excess weight — In relation to the previous point, excess weight leads to plaque buildup in your arteries, thus restricting blood flow to your heart. Ultimately, this affects your other organs, too, as they won’t get enough blood. To help you tackle the root cause of obesity, read “Study Challenges the Current Definition of Obesity.”

5. Boost your vitamin K2 intake — This nutrient serves as your body’s master regulator for calcium distribution, ensuring that it supports important functions instead of calcifying your arteries. That said, I recommend boosting your K2 intake via fermented foods, such as natto and homemade fermented veggies. Certain cheeses, such as Munster, Gouda, and Brie, are also rich in vitamin K2.

Frequently Asked Questions (FAQs) About Fisetin and Vascular Calcification

Q: What is vascular calcification, and why is it harmful?

A: Vascular calcification occurs when calcium builds up in artery walls, making them stiff and less flexible. This condition increases the risk of hypertension, heart attacks, and strokes, especially prevalent among adults over age 60.

Q: How can fisetin help prevent vascular calcification?

A: Fisetin, a naturally occurring flavonol found in strawberries, apples, and onions, prevents artery calcification by activating the enzyme DUSP1. This enzyme inhibits harmful signals (specifically the p38 MAPK pathway) that otherwise lead to hardened arteries.

Q: Who would benefit most from increasing fisetin intake?

A: Individuals with conditions like kidney disease, diabetes, or those experiencing excessive vitamin D intake can gain cardiovascular benefits by regularly consuming fisetin-rich foods or supplements.

Q: Beyond cardiovascular health, what other health benefits does fisetin provide?

A: Fisetin supports overall health by improving cholesterol and triglyceride levels, enhancing insulin sensitivity, lowering blood pressure, reducing oxidative stress, and exerting anticancer effects by activating the p53 tumor suppressor pathway.

Q: What dietary and lifestyle changes can I make to improve cardiovascular health?

A: To protect your heart and arteries, incorporate more fisetin-rich foods (like strawberries, onions, apples), eliminate ultraprocessed foods, increase physical activity, manage body weight, and consume vitamin K2-rich foods like fermented vegetables and specific cheeses (Gouda, Brie, and Munster).

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