Calcification – the bones of disease?

Pain is a language we barely understand. Aches and pains affect our vitality, daily decisions, and outlook on life. We brush them off as old age, stubborn strains or inherited arthritis. Our medicine cabinets feature a smorgasbord of creams and ointments that promise relief, albeit temporary. To reduce or prevent pain in the first place, we must know its roots. As I dig deeper into the research, I keep tripping over calcifications and nanobacteria – the world’s smallest life-like form and maybe the biggest discovery of the century.

These phenomena are not officially ‘living’ and are properly referred to as calcifying nanoparticles. They are one billionth of a meter in diameter – barely visible under the electron microscope. In the right conditions, these nanoparticles can bind our proteins, crystallize our minerals, and oddly resemble bacteria. They show up as primary suspects in atherosclerosis, kidney stones, prostatitis, periodontal disease, and arthritis. These confounders are even found in fossils and Martian meteorites, causing us to rethink the definition of life. Calcifying nanoparticles have built up our world, and seem to be involved in taking us down.

We have heard a lot about calcification of arteries in heart disease. Now, calcification of arteries and joints have been determined as associated conditions. In one report, arterial calcification was higher in patients with rheumatoid arthritis as well as lupus. Visible deposits of calcium are seen on x-rays in 50% of the population over age 85. In osteoarthritic joints, researchers found calcium phosphate crystals in over half of the samples of synovial fluid, and it appears that the calcification occurs long before the cartilage breaks down. Even more surprising is the discovery that calcification of certain nanoparticles may be infectious, self-replicating, and resistant to most antibiotics, heat, and γ irradiation.

If we dissect calcifying nanoparticles, they are basically various formations of calcium phosphate crystals. They show up as the essence of our teeth and bones, as a food additive, and as a translucent gemstone for jewelry-making. But in soft body tissues and arteries where they don’t belong, they wreak havoc while exuding a slime that causes inflammation. The debates about these elusive structures are getting hotter as calcification shows up in diabetic neuropathy, HIV, cardiovascular disease and newly-associated obesity.

Not all crystals are created equal. Doctors are detecting malignant breast calcifications that are made of calcium phosphate and may associate with nanobacteria. Benign calcifications appear to be made of calcium oxalate, the same crystals that make up kidney stones. The variations in crystals and malignancy spawn many unanswered questions about how they spread, when they cause inflammation, and why they result in disease in some people more than others.

So why do nanoparticles calcify? This question is baffling researchers who are still scurrying to control, calculate, and classify the particles within their wide assortment of conditions. One study hints at the imbalance of metabolism and the body’s use of oxygen for energy. Spanish scientists examined how calcifying nanoparticles depend more on the environment than we realize. A big factor in their development appears to be mineral levels and protein-to-mineral ratios; research shows that they assemble best in low protein-to-mineral ratios. This mineralization plays a role in other crystallizations such as calcium oxalate, according to another study.

We may not be able to understand calcifying nanoparticles, but can we stop them? A recent review outlines an exciting range of treatments including chelation therapy, drug therapy, light therapy, and herbs like Nigella sativa (black) seeds. To supplement these advances and speed things along, I have outlined some experimental nutritional approaches to reducing or preventing calcification where it may have some effect.

Test and normalize calcium-phosphate levels

Calcium and phosphate fuel these little balls of fury. While most of us supplement with calcium or vitamin D to improve our bone density and risk of fracture, new research challenges this assumption. New research indicates that calcium supplements increase the risk of heart attack. Milk may not always do a body good, particularly when 30-50 million people are lactose intolerant. Foods highest in calcium include dairy, black and navy beans, dark leafy vegetables, salmon, fortified cereals, and almonds. This chart shows quite a range of foods.

Phosphate absorption in the blood directly affects vascular calcification. Phosphate requires the help of Pit-1, a transport protein that is stimulated by excess phosphate, calcium, insulin, and growth factors. Excess phosphates bind with calcium and makes the body think it needs to create more calcium. This calcium is pulled from bones and teeth to try to maintain balance with the phosphates, increasing the risk of calcium-related disease. We are seeing an unprecedented increase in phosphate consumption through baked goods, soda, frozen meals, snack bars, and cereals. We have been oblivious to the increase of phosphorus additives which has doubled since the early 1990s in the American diet. The calcium-phosphate mineral imbalance seems to affect some individuals more than others, and can silently impact conditions like kidney disease. Researchers also found an association between inflammation (through high hsCRP levels) and calcium, phosphate, and calcium phosphate. Australian specialists provide a thorough discussion of how these minerals affect renal bone disease – a general term for diseases that include soft tissue calcification. It is important to identify your current blood levels and consult with a health professional to restore balance. While a clear picture can be difficult through blood tests, new technology like the Coronary Calcium Scan or CT Heart Scan can detect calcium deposits in your arteries.

Tackling nutrition to balance blood mineral levels is challenging to say the least. Foods have different absorption rates in the body and absorption is influenced by other physical factors. Body mass index, dietary fat intake, vitamin D levels, and parathyroid levels can increase calcium absorption; fiber intake, alcohol consumption, exercise, and constipation can decrease calcium absorption.  A very useful list of vegetarian foods reveals the foods requiring the smallest servings that are closest to milk in absorbable calcium: tofu, turnip greens, Chinese cabbage, kale, rutabaga, white beans, and broccoli.

Similarly, there are major differences between foods and the absorption of their phosphates in the body. One review showed that breads, nuts, beans, and chocolate have only a 10-30% absorption, though yeast enzymes release the phosphorus more than cereals. Milk, yogurt, cheese, eggs, fish, poultry, and beef have a 40-60% absorption rate – higher when phosphates have been added. Over 90% of phosphorus in food additives, processed cheese, and cola drinks may be absorbed. In a large study, women who drank cola suffered from lower bone density, likely due to cola’s phosphoric acid. Foods highest in phosphate include baking powder, bran cereals, dry milk (in many baking and pudding mixes), soy protein isolate, most cheeses and cheese products, many nuts, baked goods, cocoa powder, meat pickling ingredients, carbonated cola drinks, ice cream, jams and jellies, and other processed foods. RDA for phosphorus in adults is 700 mg, but this is difficult to measure when companies are not required to put phosphorus content in their Nutrition Facts panel unless it is added as a nutrient supplement. Use the Nutrition Data database to find more details on the nutrition in food products. The Mayo Clinic offers suggested alternatives for high-phosphorus foods

The phosphate connection to ADHD has been extensively researched by Hertha Hafer. A more recent study has associated organophosphate pesticides to ADHD.

Check your parathyroid gland activity

The parathyroid gland helps regulate the body’s calcium balance. Abnormalities associated with the parathyroid hormone (PTH) can cause vascular calcification in kidney disease, possibly linked to the reduced expression of a calcium-sensing receptor. This receptor is part of cells throughout the body – particularly arteries, endothelial cells, and smooth muscle cells – where we seem to be struggling with calcification-oriented disease. A new class of drugs called calcimimetics aims to control these receptors and subsquently prevent calcification. Mutations of the calcium-sensing receptor (CaSR) are being linked to hypercalcemia and a disease called sarcoidosis.

Check for conditions related to calcification

Calcified granulomas are nodes of inflammation and can indicate underlying diseases like sarcoidosis, tuberculosis, and Crohn’s disease. Breast calcifications may also indicate risks for heart disease. Autoimmune diseases like Raynaud’s Syndrome have been associated with soft tissue calcifications.

Even tendons may be prone to calcification. One study revealed calcified lesions inside tendons injured through repetitive motion in occupations or sports. According to some observations in radiology, calcification is more common around injured tissue – though the inability to detect smaller calcifications in the body may skew this perspective.

This poorly-understood condition features a clumping of inflammatory cells that may or may not produce painful symptoms. While the lungs and lymph nodes are most commonly affected, lumps can affect the heart, liver, joints, skin, brain, and eyes. Mycobacteria have been detected in some sarcoidosis granulomas, hinting again at possible bacterial association. Calcifications can form on both injured and non-injured tissues, either locally or throughout the body.

Keep an eye on vitamin D studies

Vitamin D generally increases absorption of calcium and phosphorus, but both excess and deficiency are linked to vascular calcification. High phosphate levels will suppress vitamin D activity, which may be a concern for those taking supplements. Further studies are needed to determine optimal levels of vitamin D to prevent harmful mineralization.

Get sufficient alpha-lipoic acid

Alpha-lipoic acid is an antioxidant that is known to improve diabetic neuropathy. According to recent studies, ALA also prevents vascular calcification in mice – perhaps explaining the reason it works well for neuropathy.

Balance protein-to-mineral ratios

• Since cell cultures mineralized with lower protein-to-mineral ratios, controlling this through nutrition and supplements might be a novel approach. In the case of excess calcium or phosphate, this may be theoretically offset by reducing intake and raising protein levels in the body.

• Amino acids are the building blocks of protein. In cases of malnourishment, supplementation may theoretically help decrease crystallization by increasing the protein-to-mineral ratio by boosting protein levels. Again, consult with a health professional to track how your body absorbs any supplements.
• Increasing dietary protein such as lean meat and fish, nuts, and beans may help increase the protein-to-mineral ratio naturally.
• Increasing hygiene will keep your immune system at rest and antibodies low. In turn, essential blood proteins like albumin will remain high enough to regulate blood volume. Albumin also decreases with dehydration, kidney disease, liver disease, and malnutrition.

Add more lemons

Human heart valves were decalcified with citric acid, an organic acid highest in lemons and limes.  It is not surprising that lemon juice (and olive oil) is a common remedy for kidney stones – accumulated calcium oxalate.

Take vitamin K2 (Menaquinone-7)

Vitamin K2 helps put calcium into the bones where it belongs. It prevents arterial calcification in animals and shows great potential in humans. It is being studied as a safer replacement for Coumadin and essential vitamin for long-term cardiovascular health. (Coumadin blocks all vitamin Ks.) Dietary intake of vitamin K2 is also associated with reduced cancer mortality in a large European study.

Take vitamin E – tocopherols + tocotrienols

Vitamin E and K2 appear to prevent the calcification (calcium + phosphate) in the arteries in one study. Vitamin E-deficient diets were also associated with decreased calcium deposits in bones. Different forms of vitamin E, including tocopherols and tocotrienols, are important to the bones in preventing osteoporosis. Tocotrienols have multiple anticancer effects as well. New research is necessary to determine optimal dosage and forms of vitamin E to both protect bones, avoid calcification outside the bones, and prevent other diseases.

Increase magnesium

New studies are explaining that magnesium may bind to excess phosphate and reduce arrhythmias and vascular calcification. Research associated higher magnesium blood levels may Doctors also hypothesize that lower magnesium-to-calcium levels in the blood may associate with increased risk of breast cancer. Magnesium levels can be increased through supplements, magnesium-rich foods, and Espom salt baths where intestinal absorption may be a problem.

Lower oxalate intakes where kidney stones are a problem

Avoiding high-oxalate foods can benefit cases where the body is prone to forming calcium-oxalate crystals. Calcium oxalate is another form of mineralization in the body that typically appears as kidney stones, but it can also surface in soft tissue as periodontis or cardiac problems.  An enzyme deficiency can be involved, preventing proper breakdown of oxalate. In this case, vitamin B6 is typically effective in stabilizing or reversing the condition. Spinach, rhubarb, strawberries, chocolate, wheat bran, nuts, beets, and tea are the foods highest in oxalate, though many others may affect sensitive individuals. Certain health foods like ginger, cinnamon, amaranth, and parsley are also high in oxalate.  UPMC has a list of low to high-oxalate foods for reference.

Lower glucose that may be stimulating calcification

A new study showed that high glucose levels increase smooth muscle calcification in cell samples. This relationship may explain the higher incidence of vascular calcification in diabetes, chronic kidney disease, and metabolic syndrome. Use the glycemic index/load database to check values easily.

Normalizing the nitric oxide process (and inflammation) through amino acids

Nitric oxide (NO) is an essential molecule that usually keeps us in balance. Blood pressure, memory, insulin, and other processes are regulated by nitric oxide. However, our immune systems are quite particular about nitric oxide levels. Insufficient or malfunctioning production of NO is linked to a range of conditions like diabetes, heart disease, and arthritis. Cancer drugs are trying to influence nitric oxide, but they struggle because NO can be both helpful and harmful in disease. In cases like lupus, for example, reduced glutathione can lead to excessive nitric oxide and systemic inflammation. As with most biological processes, there is a delicate balance to maintain for optimal health.

L-lysine inhibits nitric oxide production and appears to play a role in reducing the associated inflammation. In one study, lysine helped decrease calcification in heart valve materials. L-lysine is a readily available amino acid supplement, but it is not clear how it exactly behaves in the body to reduce inflammation. Lysine is high in poultry, fish, shellfish, and game meat.

We do know that L-lysine’s magic is dependent on L-arginine, which helps produce nitric oxide in the body. L-arginine is highest in shellfish, poultry, game meat, buffalo, seaweed, spinach, and pumpkin seeds. In fact, low levels of a form of arginine are linked to fatal strokes. As with all vitamins, minerals, and amino acids, supplementation cannot always guarantee absorption or wellness. In addition, certain vitamins or minerals must be consumed with or without others to be effective. Proper testing and professional guidance is essential.

Try anti-lithic herbs

Herbs that may prevent the formation of stones in the urinary system include gravel root and uva ursi (bearberry). It is not clear if these herbs would help reduce calcification outside of the kidneys. Other herbs like dong quai, devil’s claw, and juniper may prevent arthritic calcification.

Tumeric reduces inflammation from cartilage calcification

In a detailed study of cultured bovine cartilage cells, turmeric inhibited nitric oxide (and subsequent inflammation) in cartilage stimulated with calcifying nanoparticles. Turmeric has been proven to inhibit inflammation in multiple ways. Supporting studies also showed that nitric oxide inhibitors can inhibit progression of osteoarthritis.

Green tea decreases calcium deposits

While green tea is noted for preventing inflammation in arthritic joints, this may be related to the reduction in crystallization. One study found that green tea inhibited calcium oxalate deposits, and another study associated green tea with reduced artherosclerosis. A recent review of green tea in Western medicine highlights the progress and promise of green tea.

Know the risks of drugs or treatments

If you’ve had an MRI with an intravenous contrasting agent, you’ve probably had a dose of gadolinium. Japanese researchers found a link between gadolinium and calcium deposits. The popular blood-thinning drug Coumarin was also associated with vascular calcification. Tissue calcification has been experienced in cases of cosmetic parrafin injections, though they can be misdiagnosed as cysts or tumors.

Risks of nanoparticles used in therapy and products

Ironically, nanoparticles are the brand-new transportation of choice for delivering drugs into the body and fighting cancer. They are widely used in body products like sunscreen and anti-aging creams, but they may be harming as much as helping. Though research on the long-term effects of exposure is limited, one study described the long-term increase of IgG antibodies after eye exposure to calcifying nanoparticles. Heightened immune responses may lead to other diseases, and broader environmental impact is not understood.

Going further

• Phytoplankton prevent damage from UV rays by creating calcifications around their cells. Does calcification serve as a protective mechanism like this in our bodies?
• Bacterial growth increases with higher levels of phosphorus in drinking water. Do some bacteria thrive in high-phosphate conditions, increasing risk of calcification within the body?
• Phosphorus is released from rocks and sediments during weathering, erosion, and leaching. Sewage treatment is an even bigger source of phosphorus, as some of the phosphorus cannot be removed from wastewater. Automatic dishwasher detergent accounts for 10-12% of the phosphorus waste. How does this affect our calcium-phosphate balance?
• NASA reported that nanobacteria may play a role in the high incidence of kidney stones and bone density loss in astronauts. Calcifying nanoparticles have been found in lakes and springs on Earth. Can they pose a risk to our health outside of our bodies as well?
• Crystals have stumped scientists since the beginning of science. They share some symptoms of living organisms, not unlike the crystal growing kits at the local toy store. Can we learn more about our biology by studying crystallography and mineralogy? If we can see crystals as living organisms, can we better understand how they affect our bodies?

We have reached a point in history where we must simultaneously step in and back at the same time to solve more complex mysteries about our health. Boundaries in definition, classification, and professional discipline must be dissolved so we can study, diagnose, and treat with a clear picture. Calcifying nanoparticles may be the fuel for modern medicine and the catalyst of human disease. Can we handle the duality?