Phosphates are compounds that contain phosphorous and oxygen. They are essential to the construction of every cell in our body as phosphates make up the backbone of DNA, They form essential components in cell membranes and are essential to the proper growth of plants. Adenoside Triphosphate (ATP) is the molecule every cell uses used to store energy. Without it, we're dead meat.
Therefore we get a dose of phosphates any time we eat any meat or vegetable. These are "organic phosphates" which are deeply bound into the structure of the foods we eat--so much so that only 40-60% of the phosphate we consume is actually bioavailable. The rest goes through us undigested.
But these organic are not the phosphates that pose a threat to health. The problem phosphates are the "inorganic phosphates"--chunks of phosphate containing rock--that are added to our foods. The are commonly used as preservatives, flavor additives, and to keep cream from separating in dairy products. Phosphoric acid, which converts to phosphate in our bodies, is added to soda to keep brown sodas from turning jet black, which would make them unappealing to most people. Phosphates are also frequently used to provide the chalky white pill material that holds the supplements you buy in pill form.
Unlike the organic phosphates these inorganic phosphates are 100% bioavailable. That means if you eat 500 mg of calcium phosphate, disodium phosphate, or any of the many other inorganic phosphates added to processed foods or supplements, the whole 500 mg will be absorbed. When it is, it will go into your bloodstream where where will raise your serum phosphate level.
It has long been known that consuming inorganic phosphates can be very dangerous for people with severe kidney disease, as failing kidneys can't remove phosphates from teh blood, and these phosphates precipitate out in the kidney, destroying what little function is left. But while doctors may be aware of this, few of them know that consuming inorganic phosphates also poses a major risk to normal people, because it can promote heart disease.
We know from several well-conducted studies that there is a direct link between serum phosphate level and heart disease. As a recently published review article explains, " Higher serum phosphate levels were independently associated with coronary artery calcification, vascular stiffness, left ventricular hypertrophy, and carotid artery disease, even among individuals with normal kidney function and serum phosphate levels within the normal range."
A study that matched CAC scans to serum phosphate levels verified that rising serum phosphate levels correlated directly to rising Agaston scores in a population who had completely normal kidney function.
The most comprehensive study to investigate the impact of phosphates on heart disease was a study of the Framingham Offspring. It looked at serum phosphate levels in a group of over 3,000 normal people and then looked to see which of them had developed heart disease sixteen years later. It found that:
... a higher level of serum phosphorus was associated with an increased CVD [cardiovascular disease] risk in a continuous fashion. ... Individuals in the highest serum phosphorus quartile experienced a multivariable-adjusted 1.55-fold CVD risk ... compared with those in the lowest quartile... Serum calcium was not related to CVD risk.Does Eating Inorganic Phosphates Raise Serum Phosphate Levels?
After reading this, I could not help but wonder if those high serum phosphate levels that caused heart disease were caused by eating diets high in phosphate or whether people destined to get heart disease migh6 have high serum phosphate levels as a side effect of an undiagnosed preexisting health issue.
Could eating a diet high in phosphates be all it took to raise serum phosphate levels? This question was elegantly answered by a study published back in 1977.
In this study subjects who were allowed to eat only the foods supplied by the researchers were, for four weeks, fed a control diet free of any phosphate additives. Then, for the next four weeks, they were fed a diet that contained the identical amount of calories, protein, fat, and carbohydrate as the control diet but this diet was made up of foods containing inorganic phosphate additives, like American cheese, soda, and processed meats.
The report explains, "The average phosphorus content of the daily menu was 979 mg during the control period and 2124 mg during the test period." After a month of eating the foods with the added phosphates, the study participants blood was tested and it was found that they had experienced a dramatic rise in serum phosphates, accompanied by a decrease in serum calcium. The addition of the phosphates to their diets also caused digestive distress to many of the participants--in some cases it persisted throughout the whole study.
When their serum phosphate levels were measured, they were found to have "increased from 3.76 ±0.38 mg/100 ml during the control period to 4.43 ±0.30 mg/ 100 ml [mg/dl] during the high-phosphorus period." This was an 18% rise in serum phosphate level. So yes, upping dietary consumption of inorganic phosphates will raise serum phosphate a lot, even in completely normal people.
And it is also worth noting that the amount of phosphate being consumed by the subjects in this study is likely to be far less than that consumed by the average person today since they were being fed a controlled diet containing only 2,200 calories. Higher caloric intakes would result in higher intakes of inorganic phosphates, and higher serum phosphate levels, too. And people eating "healthy diets" who use supplements might be getting even higher amounts, since many chalky pill substrates are made mostly of dicalcium phosphate.
How Damaging Is This Added Phosphate?
The Framingham Offspring study found that in normal participants whose serum phosphate levels were in the top quarter of readings for the whole research group at the beginning of the 16 year study there was a 55% higher risk of developing cardiovascular disease at the end of the study . This is a big leap in risk, especially when it is attributed to a factor that is completely ignored by doctors, health authorities, and food companies.
Though we can't be confident in comparing the blood phosphate levels in the 1977 diet study and the Framingham Offspring study, as using different lab techniques will give different reference ranges, it's worth noting that the serum phosphate value representing beginning of the highest quartile in the Framingham Offspring Study--the level at which cardiovascular risk was 55% higher--was only 20% higher than the top of the lowest quartile.
So since we have seen that boosting the phosphate intake of a 2,200 calorie diet can easily achieve an 18% rise in serum phosphate levels, it seems very likely that dietary consumption of phosphates, alone, is enough to boost serum levels into the range that correlates with a higher risk of heart disease.
Is it the Phosphates Causing Heart Disease or Are They A Lifestyle Marker?
Since inorganic phosphate intakes rise dramatically when people eat diets high in fast food and soda, it would be easy to dismiss the link between serum phosphates and heart disease as being due not to the phosphates themselves, but to the unhealthy diet that results in those high serum phosphate levels. In short, to point to serum phosphates as a marker of a diet rich in junk food.
But there is some other research that contradicts this argument. The researchers who published the Framingham Offspring Study cite a study that found that "... higher phosphorus levels increase the propensity of mineral deposition in vascular smooth muscle cells in vitro." That study found that
HSMCs -[Aortic Smooth Muscle Cells] cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition.Furthermore, exposure to high levels of phosphates induces a phenotypic transformation of vascular smooth muscle cells into osteoblast-like cells that express biochemical markers characteristic of the cells that turn into bone.
What this means in plain English is that in a petri dish, cells from heart arteries were fine when exposed to normal levels of phosphates, but when the levels rose to abnormally high levels the artery cells started to act like bone stem cells and fill up with tiny bits of rock. The higher the amount of phosphate they were exposed to, the more rock.
The Framingham researchers also cite a study showing that "higher serum phosphorus levels increase circulating PTH [parathyroid hormone] levels even in healthy individuals," pointing out that "Higher PTH levels may be proinflammatory" as they raise the level of a substance, IL-6, linked to heart disease.
These findings suggest that the problem is that when you eat too much phosphate-containing rock, that rock ends up floating around your bloodstream until it precipitates out in your heart muscle (and other) cells.
Phosphate, Vitamin D, and Niacin
An interesting side note to the issue of high serum phosphate is the finding that rising serum phosphates will lower Vitamin D production as Vitamin D is one of the regulators of blood phosphate levels. (Discussed HERE). If you have abnormally low Vitamin D levels when not supplementing Vitamin D, this could be pointing to the fact that your serum phosphate level is unhealthily high.
In patients with kidney failure, there is some evidence that supplemental niacin lowers the very high serum phosphate levels characteristic of kidney failure, though there is no research to answer the question of whether niacin lowers phosphate levels in people with normal kidneys. But it makes a lot more sense to lower serum phosphate levels by cutting out of your diet as much inorganic phosphate as possible rather than to drive with one foot on your physiological accelerator and one on the brake, which is what you do when you attempt to lower these levels by taking a supplement while consuming the phosphates.
What's Next?
I'll be writing more about the role of inorganic phosphates in our diets and what we can do to achieve normal serum phosphate levels. For now, your homework is to start reading labels for all the foods and supplements you consume, to see how many items you eat each day contain added inorganic phosphate.
Since I started doing this, back when I published my first post about the dangers of high phosphate levels, I've been at first surprised, and then horrified, to see just how much of what I have thought of as "healthy" foods and supplements are full of these dangerous, inorganic phosphate minerals.
Jenny said...
However, it is likely this is because Avandia and Actos CAUSE heart failure, rather than that these other drugs prevent it. People are rarely put on both families of drugs at once.
It may also be because these GLP-1 related drugs are mostly prescribed to affluent, younger people with diabetes and good health insurance, while poorer people are put on the cheap sulfonylurea drugs which are now known to raise the risk of heart attacks.
So plaque probably is some byproduct of an adaptation in the way humans process calcium--probably one that is a byproduct of the genetic changes that led to our species' distinctive bigger brains and smaller digestive tracts.
The Paleo diet is useful in helping cut back on junk food, but the idea that ancient humans were healthier than we are is almost certainly a fantasy. The life expectancies of junk food chomping modern day humans is far longer than that of any pre-agricultural peoples, if only because we have effective treatment for injuries and contagious diseases.
I remember playing outside in the summer in 1954, and the spray truck passing by spraying huge clouds of DDT. We would take deep breaths of the stuff which had a curious smell. Later, before we went to sleep, my mom would spray my bedroom with it and then I'd crawl right into bed.
Maybe my high blood pressure isn't so mysterious!
Reuters: Scientists find how deadly virus infects human cells
http://www.medpagetoday.com/PrimaryCare/Diabetes/37890
http://www.latimes.com/business/money/la-fi-mo-butterfly-bakery-sugar-20130314,0,7328666.story
http://www.pbs.org/newshour/bb/environment/jan-june13/epa_03-15.html
It produced only 4% more weight loss than a worthless placebo. That's 8 lbs lost more than on placebo for someone weighing 200 lbs--which you can easily accomplish without drugs by eating a very low carb diet for a month.
Note that this was on a high dose regimen, and that this drug has been connected with both thyroid cancer and pancreatitis at normal doses.
http://www.reuters.com/article/2013/03/18/us-novonordisk-idUSBRE92H0EY20130318
Practical takeaway: let your kids play outside in real dirt when they are young and don't use antibiotic soaps.
http://www.sciencedaily.com/releases/2013/03/130318203334.htm
Rosuvastatin (e.g. Crestor) at doses of 10mg or higher.
Atorvastatin (e.g. Lipitor) at doses of 20mg or higher.
Simvastatin (e.g., Zocor) at doses of 40mg or more.
http://www.cbc.ca/news/health/story/2013/03/19/statin-kidney.html
Also note that they did measure blood levels after the supplementation which ended up on average in the low end of the normal range at 32 ng/ml. They did not observe what happens if you oversupplement and reach the much higher levels where nasty things can start happening to your calcium metabolism.
http://www.sciencedaily.com/releases/2013/03/130320212824.htm
http://diabetes.webmd.com/news/20130325/glucose-meter-recall
http://www.medpagetoday.com/Endocrinology/Diabetes/38139
You can lower your blood sugar dramatically without using any technology but a blood sugar meter by using this technique:
How to Lower Your Blood Sugar
Science Daily: Scientists Discover How Drug Prevents Aging and Cancer Progression