Apo E4 and sterols: Lethal combination?

11. February 2011 William Davis (24)
Phytosterols, or just "sterols" to its friends and neighbors, are a group of cholesterol-like compounds that are abundant in the plant world. Lately, however, sterols have proliferated in the processed food supply, thanks to the observation that sterols reduce LDL cholesterol when ingested by humans.

This must mean that sterols are good for you.

Uh oh. Wait a minute: There is a rare disease called sitosterolemia in which there is unimpeded intestinal absorption of all sterols ingested through diet. They must have really low LDL cholesterols! Nope. They develop coronary disease--heart attacks, angina, etc.--in their late teens and 20s. In other words, if sterols gain access to your bloodstream, they are bad. Very bad.

Conventional thinking is that only a modest quantity of dietary sterols gain access to the bloodstream. But there are two potentially fatal flaws in this overly simplistic line of thinking:

1) What happens when you load up your diet with "heart healthy" sterols, such as those in "heart healthy" margarines, mayonnaise, and yogurt, effectively increasing sterol intake 10-fold?

2) What happens in people with the genetic pattern, apo E4, that is carried by 25% of the general population that permits much greater intestinal absorption of sterols?

My prediction: Despite the fact that sterols reduce LDL, they may, in certain genetically-susceptible people, such as those with apo E4, increase risk for heart disease: heart unhealthy.

Here are two studies that suggest that greater sterol absorption in people without sitosterolemia are at higher risk for heart disease:

Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

Glucomania

8. February 2011 William Davis (52)
As I suggested in a previous Heart Scan Blog post, a glucose meter is your best tool to:

1) Lose weight
2) Cure diabetes
3) Reduce or eliminate small LDL particles
4) Achieve anti-aging or age-slowing effects

But it means getting hold of a glucose meter and applying it in a very different way.

Diabetics typically check fasting morning glucose and again several times during the day to assess medication effects. But you and I can measure blood glucose to assess the immediate effects of food choices--two very different approaches.

The concept is simple: Check a blood glucose just prior to a food or meal of interest, then one hour after finishing.

Let's take two hypothetical breakfasts. First, oatmeal, a so-called "low-glycemic index" food. Slow-cooked, stone ground oatmeal with skim milk, a handful of walnuts, just a few blueberries.

Blood glucose just prior: 95 mg/dl
Blood glucose one hour after finish: 175 mg/dl

I made those numbers up, but this is a fairly typical response for many adults. (This is why "low-glycemic index" is an absurd notion.) This kind of response causes 1) glycation, the adverse effects of glucose modification of proteins that leads to cataracts, kidney disease, cartilage damage and arthritis, atherosclerosis, skin wrinkles, etc., 2) high insulin response that cascades into fat deposition, especially visceral fat ("wheat belly"), and 3) glucotoxicity, i.e., direct damage to the pancreas that can, over years, lead to diabetes.

Next day, let's try a breakfast of 3-egg omelet made with green peppers, sundried tomatoes, and olive oil.

Blood glucose just prior: 95 mg/dl
Blood glucose one hour after finish: 93 mg/dl

This is a meal of virtually zero-glycemic index. This kind of response triggers none of the effects experienced following the oatmeal. Repeated over time and you fail to trigger glycation, you stop provoking insulin, and visceral fat mobilizes rather than accumulates: you lose weight, particularly around the middle.

We therefore aim to keep the one-hour blood glucose 100 mg/dl or less. If you start with a high fasting blood glucose of, say, 118 mg/dl, then we aim to keep the one-hour after-eating blood glucose no higher than the pre-meal.

It works. Plain and simple.

This makes the primary care docs crazy: "How dare you check your blood sugar! You're not diabetic." In truth, blood glucose meters are relatively simple devices to use. The test strips and lancets will cost a few bucks. (The meters themselves are either low-cost or free, just like Gillette sometimes sends you a beautiful new razor for free but expects you to buy the blades). These are direct-to-consumer products. While a prescription written by your doctor for a glucose meter and supplies helps insurance cover the costs, you can easily get these devices without a prescription. Some stores, like Target, keep their devices out on the shelves with the shampoo and bath soap.

Warning: Anyone taking diabetes drugs will have to consult with their doctors about the safety of such an approach. Because this approach can actually cure diabetes in some people, if you are taking some diabetes drugs, especially glyburide, glipidize, and glimepiride, you can experience dangerously low blood sugars, just as any non-diabetic taking these drugs would.

Diarrhea, runny noses, and rage: Poll results

6. February 2011 William Davis (19)
Here are the results of the week-long poll asking the question:

Have you experienced a wheat re-exposure syndrome?
Yes, undesirable gastrointestinal effects 223 (41%)
Yes, asthma or sinus problems 51 (9%)

Yes, joint pains and/or swelling 85 (15%)

Yes, emotional or other nervous system effects 59 (10%)
No, nothing, nada  107 (19%)

No. Wheat is sacred and you're all nuts  13 (2%)


There are several interesting observations to make from this informal poll. First, as I have observed, the most common wheat re-exposure syndrome is gastrointestinal, usually involving cramps, diarrhea, and lame explanations to your dinner partner.

Second most common: joint pains and/or swelling.

Third: asthma or sinus congestion.

The incidence of emotional or nervous system effects surprised me a bit. I didn't expect 10% of people to share this effect. This is an effect I also experience personally, along with the gastrointestinal consequences.

To be sure, this is a skewed poll, since many people likely come to this blog in the first place because of such issues. But I was nonetheless impressed with the relatively modest proportion of people who did not share such a re-exposure syndrome: only 19%.

Beyond the interesting numbers provided by readers, a good many also provided some fascinating and graphic comments. Here's a sample:




Sassy said:

Reflux -- starts a day later and goes for up to a week. And Bloat:2-5 inches on my waistline in a day, lasting up to three. Miserable. And why, having experienced this once, have I done it often enough to verify the connection with certainty? I am working on that one.
Anonymous said:
Wheat increased hunger with even with only a small amount. Crackers in soup was enough to set it off.

Also, when I was trying to get off wheat, I noticed that 2 eggs and 2 bacon and I could go 5 hours before hunger, or 2 eggs and 2 bacon and toast was good for three hours before hunger. That was the final step to giving up wheat. Now three years and 59 Kg [130 lbs!] loss later, there is no doubt in my mind that wheat is evil, and I do not regard it as suitable for human food. I speculate that it increases ghrelin or cortisol.

Anna said:
For me, in the two years since I began eating Gluten-Free (Low Carb for 6 years), the few times I've had re-exposure to wheat, I've experienced fast onset and intense abdominal pain (known exposure during the daytime) and heartburn, indigestion, intense nausea, and disrupted sleep (exposures during evening meal not discovered until the next day).

My husband wants to think he's fine with wheat (though I know that he has at least one gene that predisposes to celiac), but IMO, he isn't. He eats no wheat at home because that's the default, and he's OK with that. But if he goes out to dinner at a restaurant that serves "good" artisan bread, he will indulge in a few bites (he does restrict his carb intake, so it's still a limited amount). More often than not, he will sleep fitfully on those nights, snore more, and wake in the night with indigestion. He wants to bury his head in the sand and will only acknowledge the discomfort being due to eating too many carbs, not the wheat itself. I notice he sleeps fine if he eats a small amount of potato or rice. Go figure.

Our 12 yo son has been eating GF for two years also. About 6 months into GF, he unknowingly ate wheat a number of times (licorice candy laces at a friend's house), which resulted in outbreaks of canker sores in his mouth each time. He also exhibits mood and behavior changes when he eats wheat, which is what prompted me to test him for gluten intolerance in the first place.

Mark said:
If I go for 3-4 days without wheat, grains or sugar and then go out and binge on a pizza and ice cream or something like that I become explosive within 20 minutes to an hour. It's like a wheat and sugar rage.(I'm not saying this is an excuse for rage, I'm saying it has happened to me and I believe partly do to re-exposure) It seems the combination of the wheat plus sugar can be the worst.

I get red rashes around my neck sometimes right away and sometimes up to a day or later and sometimes get bad diarrhea. 
I think it can be almost dangerous to cut things like gluten and sugar suddenly out of the diet without being very serious about keeping them out. I have found it very hard to cut out wheat without binging on it later after 4 or 5 days. I don't believe that my symptoms are just psychological either.
I was also diagnosed with ADHD as a young kid and then rediagnosed with adult ADHD by 3 different doctors. I also have bouts of mania at times too. I am considering trying to go completely gluten/refined carbohydrate free to see if it helps with the symptoms and gives me some relief.

I have never been tested for celiac or gluten intolerance but I would like to be. I think it would help explain to my girlfriend, family and friends why I can't go out and eat pizza or have a beer or ice cream. Right now they all think I'm a hypochondriac. At times I have experienced an intense fatigue the next day like I can't wake up and also sharp pains in my body and headaches.
Anonymous said:
I ditched wheat a year ago after my wife was diagnosed celiac. I immediately experienced a number of health improvements (blood lipids, sleep, allergies, etc.).

Fast forward: We all suffered some inadvertent wheat exposure yesterday via some chocolate covered Brazil nuts (of all things). This accidental A-B-A experimental design resulted in the following:

1. My celiac wife experienced what she calls "the flip" within an hour of exposure (i.e., intense GI distress).
2. My five-year old son went to bed with some wicked reflux.
3. I woke up with some twinges in my lower back and an ache in my football-weary left shoulder. I was also complaining to my wife about fuzzy-headedness that refused to respond to caffeine or hydration. I could only describe it as "carb flu"...

And then I read your post!

Anne said:
Depression, agitation and brain fog if I get glutened. Some times this comes with abdominal pain and a rash on my back - I think it is dose dependent. Cross contamination with wheat is a big issue when eating out. Needless to say, I eat out infrequently and then try to stick with the restaurants that are the most aware of gluten issues.
Terrence said:
Several weeks ago, I started Robb Wolf's 30 day challenge.

The first two weeks were brutal - calling it a withdrawal flu was a massive understatement. So, I thought I would try some wheat and see what happened (could not be worse, I thought). Well, it was.

I still felt extremely crappy, but I was now MASSIVELY GASSY - AMAZINGLY GASSY, for about 48 hours - flatulence on wheels, in spades. I did not go out at all in those 48 hours - when the gas came on, it went out, LONG, and QUICKLY and LOUDLY.

I am easing back into wheat and grain free. I am gluten free today and tomorrow (Sunday and Monday). I expect to try a small amount of wheat on Thursday, then maybe a little more the following Thursday.

Donald said:
I have limited wheat consumption severely over the last 8 months. I have lost 120 pounds, no longer have bouts of illness, asthma, depression, or low energy. I also take vitamin D and other supplements that have helped (many are from your blog recommendations).

Last week I ate a small piece of cake and dessert pizza. Shortly thereafter I started sneezing, had a scratchy throat, and runny nose. I called off sick the next day for fear of being contagious. My symptoms subsided quickly and I am now attributing them to the processed flour eaten at my work luncheon. I think it was an allergic reaction since I recall having much more severe symptoms fairly regularly in my wheat eating days. Those were attributed to an "allergy" of unknown origin back then.

John said:
I suffered from Ankylosing Spondylitis, Iritis, Plantar Fasciits, etc for a number of years. I restricted carbs, especially wheat and I've been symptom free for the past two years now.
Lori said:
I found wheat to be one of the worst things for giving me gas bloating and acid reflux, and I'd had sinus and nasal congestion my whole life. When I ate that cookie, it just re-introduced old problems. I can occasionally eat a gluten-free, grainy goody at my party place without any side effects. I also have a little sprouted rice protein powder every day.

Another odd thing about wheat: it was hard for me to stop eating it once I started. I could go through a whole box of cookies in one sitting, even though I wasn't a binge eater. But I can have a couple of gluten-free cookies and stop.

Paul said:
Except for one slip up this recently past holiday season, I've been sugar-grain-starch free since July 2008. Mental fog was the most noticable re-exposure symptom I had.

My mom has had the worst acid-reflux for 40-plus years. It had become so bad that she was on three medications just to deal with the symptoms. After much training and coaxing, I finally got across to her  how to totally get off wheat. Not at all to my surprise, after being wheat free for a few weeks, she lost weight and her acid reflux was GONE!

But she had been addicted to wheat for so long, she relapsed, and the reflux fire soon returned. Wheat must be akin to heroin with some people. Even though they know it's very bad for them, they can't help themselves.

Onschedule said:
Re-exposure often leads to diarrhea for me, or such a heavy feeling of tiredness that all I can do is lay down and pass out. A local pizzeria makes a darn good pie, but since I started practicing wheat-avoidance, I can't keep my eyes open after eating there. I can't say for sure that it's the wheat causing it, but definitely something in the crust. Diarrhea, on the other hand, is definitely triggered by the wheat for me.

My mom complained of gastric reflux for years, but never filled the prescriptions that her doctors would give her. I suggested wheat-avoidance- gastric reflux disappeared within 3 days and hasn't returned (has been 6 months now). I've already commented elsewhere on this blog about how much weight and bloating she has lost...

Steve said:
Interesting that I should sit down, turn on my computer and find your poll. Having gone several weeks, maybe months, avoiding gluten, I took my daughter and her boyfriend out to eat because my wife has been working late at the office lately. Although I was thinking I would just eat my steak and chicken, I succumbed to the temptation of eating about a dozen greasy, breaded shrimp that my daughter and her boyfriend ordered. It's 1:39am and I still do not feel sleepy. My left nostril is completely blocked, my stomach feels bloated, really, really full and I've been burping. In your poll I checked sinus problems but could have chose gastrointestinal or nervous problems just as well. 
A few weeks ago my daughter brought home a pizza and, once again, despite my knowing that I shouldn't, I ate a couple of pieces. I was sick for two days. The pain in what I think was my transverse colon was so bad I thought I might have to go to ther emergency room. Before I ate the pizza I had never gone grain-free that long before. I did this after reading Robb Wolf's book. 
I AM CONVINCED. No more wheat for me! Please, Lord, give me strength.
LV said:
What don't I experience! I typically avoid wheat (and gluten for that matter) as I'm pretty sure it makes me sick, but when I slip (or someone else slips me some) I end up with massive amounts of joint swelling and tenderness, diarhea, cramping, gas, bloating and brain fog. I'm absolutely miserable. Just that alone is enough to keep me off gluten. I have RA, so if I have repeated exposures I'll have a flare which SUCKS!

The perfect Frankengrain

4. February 2011 William Davis (25)
Pretend I'm a mad food scientist. I'd like to create a food that:

1) Wreaks gastrointestinal havoc and cause intractable diarrhea, cramps, and anemia.
2) Kills some people who consume it after a long, painful course of illness.
3) Damages the brain and nervous system such that some people wet their pants, lose balance, and lose the ability to feel their feet and legs.
4) Brings out the mania of bipolar illness.
5) Amplifies auditory hallucinations in people with paranoid schizophrenia.
6) Makes people diabetic by increasing blood sugars.
7) Worsens arthritis, such as osteoarthritis and rheumatoid arthritis.
8) Triggers addictive eating behavior.
9) Punishes you with a withdrawal process if you try to remove it from your diet.

I will develop a strain that is exceptionally hardy and tolerates diverse conditions so that it can grow in just about any climate. It should also be an exceptionally high yield crop, so that I can sell it cheaply to the masses.

Now, if my evil scheme goes as planned, I will then persuade the USDA that not only is my food harmless, but it is good for health. If they really take the bait, they might even endorse it, create a diet program around it.

Dag nabit! Such a plan has already been implemented. Another evil food scientist already beat me to the punch. The food is called wheat.

Diabetes: A study in aging

3. February 2011 William Davis (0)
Diabetics experience long-term health difficulties, including atherosclerosis/heart attacks, peripheral vascular disease, hypertension, cataracts, kidney disease, neuropathies, male erectile dysfunction, osteoarthritis, and colorectal cancer. They also die, on average, 10 years earlier than non-diabetics.

In effect, diabetics compress their lives into a shorter period of time. They experience all the "complications" of aging at a younger age. People without diabetes, of course, can develop atherosclerosis, cataracts, kidney disease, etc., but they tend to do so later in life compared to diabetics.

One index of the rate of aging (but not chronologic age itself) is hemoglobin A1c, or HbA1c, a "moving average" of glycated hemoglobin, i.e., glucose-modified hemoglobin. Blood glucose glycates hemoglobin linearly and irreversibly; measuring HbA1c thereby provides an index of the last 60 or so days average blood glucose.

To put HbA1c values into perspective:

Average HbA1c of hunter-gatherers: 4.5%
Average HbA1c for Americans: 5.6%
American Diabetes Association definition of diabetes: 6.5% or greater
American Diabetes Association definition of adequate control of diabetes: 7.0% or less

Why do diabetics age faster? There are likely several reasons. One important reason is glycation, as indexed by HbA1c. Glycated proteins in the lens of the eye causes cataracts. Glycated proteins in cartilage leads to arthritis. Glycated LDL particles (apo B) leads to atherosclerosis. Glycated nerve cells causes neuropathy. And so on.

If glycation underlies many of the phenomena of aging, then we might surmise that:

1) The less you glycate, the slower you age.
2) The more you glycate, the faster you age.

Therefore, the higher the HbA1c, the faster you are aging.

What foods increase HbA1c? Carbohydrates. That bowl of slow-cooked, stone ground oatmeal? A one-hour after-eating blood sugar of 170 mg/dl is common. Your doctor says that's okay because it's below 200 mg/dl and you don't "need" medication yet.

Fish oil: The natural triglyceride form is better

2. February 2011 William Davis (43)
If you have a choice, the triglyceride form of fish oil is preferable. The triglyceride form, i.e., 3 omega-3 fatty acids on a glycerol "backbone," is the form found in the body of fish that protects them from cold temperatures (i.e., they remain liquid at low ambient temperatures).

Most fish oils on the market are the ethyl ester form. This means that the omega-3 fatty acids have been removed from the glycerol backbone; the fatty acids are then reacted with ethanol to form the ethyl ester.

If the form is not specified on your fish oil bottle, it is likely ethyl ester, since the triglyceride form is more costly to process and most manufacturers therefore boast about it. Also, prescription Lovaza--nearly 20 times more costly than the most expensive fish oil triglyceride liquid on a milligram for milligram basis--is the ethyl ester form. That's not even factoring in reduced absorption of ethyl esters compared to triglyceride forms. Remember: FDA approval is not necessarily a stamp of superiority. It just means somebody had the money and ambition to pursue FDA approval. Period.

Taking any kind of fish oil, provided it is not overly oxidized (and thereby yields a smelly fish odor), is better than taking none at all. All fish oil will reduce triglycerides, accelerate clearance of postprandial (after-eating) lipoprotein byproducts of a meal (via activation of lipoprotein lipase), enhance endothelial responsiveness, reduce small LDL particles, and provide a physical stabilizing effect on atherosclerotic plaque.

But if you desire enhanced absorption and potentially lower dose to achieve equivalent RBC omega-3 levels, then triglyceride forms are better.

Here are cut-and-pasted abstracts of two of the studies comparing forms of fish oil.

Bioavailability of marine n-3 fatty acid formulations.

Dyerberg J, Madsen P, Moller JM et al. 
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.
(Full text of the Dyerberg et al study made available at the Nordic Naturals website here.)



Eur J Clin Nutr 2010 Nov 10. 

Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.

Neubronner J, Schuchardt JP, Kressel G et al. 
Institute of Food Science and Human Nutrition, Leibniz Universität Hannover, Am Kleinen Felde 30, Hannover, Germany.

Abstract

There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P < 0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P < 0.001); t(6): 197 versus 171% (P < 0.01)). Conclusion: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.

Diarrhea, asthma, arthritis--What is your wheat re-exposure syndrome?

30. January 2011 William Davis (52)
Have you experienced a wheat re-exposure syndrome?

As I recently discussed, gastrointestinal distress--cramps, gas, diarrhea--is the most common "syndrome" that results from re-exposure to wheat after a period of elimination.

Others experience asthma, sinus congestion and infections, mental "fogginess" and difficulty concentrating, or joint pains and/or overt swelling.

Still others say there is no such thing.

Let's take a poll and find out what readers say.

Marathoners, triathletes, and heart disease

30. January 2011 William Davis (0)
Curious thing: People with lipoprotein(a) gravitate towards elite levels of exercise.

I tell my lipoprotein(a) patients that, if they want to see a lot of other people with lipoprotein(a), go to a marathon or triathlon.

This effect applies more to males than to females, just as the fascination with numbers seems to be confined to men, too. That's why I've posted in past about the "prototypical" lipoprotein(a) male.

I believe this is a big part, perhaps the only, reason why there seems to be a modest increased risk for cardiovascular events despite high exercise levels in marathoners. It has nothing to do with the exercise itself; it has to do with the kind of people who choose to exercise at this level.

The best fish oil

29. January 2011 William Davis (30)
The best fish oils available are the liquid forms. Contrary to many people's expectations, the best liquid fish oils have no fishy odor or taste.

I use a lot of liquid fish oils because of the higher doses we use in the Track Your Plaque program, as well as our strategy of high-dose fish oil to reduce lipoprotein(a). Women, in particular, don't like taking the oodles of capsules required to achieve the higher doses we need. So the ladies really like the liquid forms.

The best liquid fish oils are non-fishy, highly-concentrated, and come in the better absorbed triglyceride form. Many capsules, including prescription Lovaza, are the less well-absorbed ethyl ester form. Several studies, such as this one, have now demonstrated that the naturally-occurring triglyceride form yields higher blood (RBC) levels of omega-3 fatty acids, likely due to more efficient digestion via pancreatic lipase.

While there are many good forms of fish oil and only a few bad, these are the best of the best:

Pharmax
The Pharmax Finest Pure Fish Oil with Essential Oil of Orange contains 1800 mg EPA + DHA per teaspoon. This is the preparation I've been taking.

Nordic Naturals
The Nordic Naturals lemon-flavored ProOmega Liquid contains 2752 mg EPA + DHA per teaspoon, the most concentrated of any fish oil I've seen.

(This list is not exclusive. These are just two brands I've used extensively with good results.)

These highly-concentrated, triglyceride forms are more expensive, due to their concentrated nature. 1 teaspoon Pharmax fish oil, for example, provides an equivalent quantity of omega-3 fatty acids as 6 standard fish oil capsules on a milligram for milligram basis, but more like 8 to 9 capsules when absorption efficiency is factored in. The triglyceride form is also more laborious to manufacture. On our Track Your Plaque Marketplace, our Pharmax 500 ml runs $58.95 list. (500 ml provides 100 teaspoons or 600-capsule equivalent.)

Note that, minus the protection of the capsule, liquid fish oils will oxidize if not refrigerated. So be sure to keep your liquid fish oil in the fridge.
Increased blood calcium and vitamin D

Increased blood calcium and vitamin D

21. June 2010 William Davis (50)
Conventional advice tells us to supplement calcium, 1200 mg per day, to preserve bone health and reduce blood pressure.

Here's a curious observation I've now witnessed a number of times: Some people who supplement this dose of calcium while also supplementing vitamin D sufficient to increase 25-hydroxy vitamin D blood levels to 60-70 ng/ml develop abnormally high levels of blood calcium, hypercalcemia.

This makes sense when you realize that intestinal absorption of calcium doubles or quadruples when vitamin D approaches desirable levels. Full restoration of vitamin D therefore causes a large quantity of calcium to be absorbed, more than you may need. In addition, two studies from New Zealand suggest that 1200-1300 mg calcium with vitamin D per day doubles heart attack risk.

We have 20 years of clinical studies demonstrating the very small benefits of supplementing calcium to stop or slow the deterioration of bone density (osteopenia, osteoporosis). These studies were performed with no vitamin D or with trivial doses, too small to make a difference. I believe those data have been made irrelevant in the modern age in which we "normalize" vitamin D.

Should hypercalcemia develop, it is not good for you. Over long periods of time, abnormal calcium deposition can occur, leading to kidney stones, atherosclerosis, and arthritis.

Until we have clarification on this issue, I have been advising patients to take no more than 600 mg calcium supplements per day. I suspect, however, that the vast majority of us require no calcium at all, provided an overall healthy diet is followed, especially one that does not leach out bone calcium. This means no foods like those made with wheat or containing powerful acids, such as those in carbonated drinks.
Tags :

Comments (50) -

  • renegadediabetic

    6/21/2010 1:18:12 PM |

    Sometimes I think that the RDAs only apply to the current high refined carb, nutrient depleting diet most americans eat.  

    This is just more proof that the current calcium "requirements" are overstated and probably intended to market dairy products or calcium fortified processed foods.

  • Katie

    6/21/2010 1:42:19 PM |

    I always thought the recommendations for supplementing with calcium were probably wrong.  I've heard that Americans eat more calcium-rich foods and supplement with more calcium than other Western countries, but yet suffer from the highest amount of osteoporosis/osteopenia.  

    This wouldn't surprise me, given the importance of having the right amounts of calcium, Vitamin D, and Vitamin K2.  I've seen other doctors/researchers recommend that Vitamin D always be taken in connection with sufficient intake of Vitamin K2 to help prevent hypercalcemia.  I do not supplement with calcium, but I do supplement with D3 and K2 and have had no problems

  • Anonymous

    6/21/2010 1:45:19 PM |

    Dr. Davis is wheat a bad idea because of the phosphates which demineralize bones ? If so then lentils and peas and beans would be quite high in phosphates too? would the recommendation be to lower their consumption as well?

    Thanks.!

  • PJNOIR

    6/21/2010 2:56:32 PM |

    Calcium as a supplement is one of the toughest to assimilate in the body- I can't see how an accurate number can be assessed as too much (or too little)

  • scott

    6/21/2010 3:28:53 PM |

    I wonder how much calcium is in Gerolsteiner Water.  Dr. Davis has recommended this in the past, but probably for the magnesium content.

  • Anonymous

    6/21/2010 3:37:16 PM |

    1) It would seem that anyone speaking of vitamin D, is being a little misleading as we should most likely be talking about D-2 or D-3. Or never talking about D-2 and always about D-3 as it is the more bio-active.
    2) Increase K-2 to take care of the D-3 / calcium problem.
    3) Blood tests to keep track of all three of them.

  • miannotta

    6/21/2010 4:51:37 PM |

    Would supplementing with vitamin K2 help alleviate the problem of too much calcium in the blood? It's function is to redirect blood calcium to the bones. Or is the jury still out on this?

  • Anonymous

    6/21/2010 5:20:33 PM |

    This is a point also made in the current posting of "Diabetes Update"

  • Steve

    6/21/2010 6:11:04 PM |

    Apparently alot of people are reporting issues with vitamin d supplementation. You may have hit the nail on the head, Dr Davis. Here is a website that has over 200 comments from people experiencing issues.
    http://ctheblog.cforyourself.com/2008/12/overdosing-on-vitamin-d-side-effects.html

    Steve

  • Jenny

    6/21/2010 6:55:53 PM |

    Since I ran into just this problem (and blogged about it elsewhere) I want to add this:  You don't have to be supplementing with pills to run into this problem.

    If you are eating a classic low carb diet and eating cheese rather than meat for much of your protein your calcium intake can get high pretty fast.

  • Bobber

    6/21/2010 7:19:02 PM |

    Are you familiar with Dr. Cordain's work on Acid/Base balance?
    http://thepaleodiet.com/nutritional_tools/acid.shtml

  • Anonymous

    6/21/2010 10:17:14 PM |

    http://www.ncbi.nlm.nih.gov/pubmed/19113911

    Men don't need more than 626 mg/day calcium, and women with D > 20 ng/ml don't need more than 566 mg/day.

  • Jessica

    6/22/2010 12:43:32 AM |

    We usually recommend that individuals stop taking a calcium supplement once they've reached the target D level (70-90 ng/mL).

    We always draw a serum calcium with a 25(OH) level.

    Detected several cancers in our patients this way (hypercalcemic prior to starting D supplementation).

    Also, I'm about 8 months pregnant with our first child and you think cardiology is behind the times with Vitamin D, try OB! They're living in the dark ages.

    Fortunately my OB is more versed than most and the fact that I take 10,000 IU daily doesn't make him too uncomfortable (obviously not since he didn't offer to check my D level...I had to ask for it).

    I'm also taking 500 mg QD of elemental magnesium (no preeclampsia for me) and (when I remember), 12.5 mg of Iodoral/week (I worry about taking it everyday due to potential for "heavy metal dumping" since I wasn't routinely taking it prior to pregnancy).

    I still take a pre-natal, but I worry more about not taking the other supplements more than i worry about missing a dose of the pre-natal.

    Thanks for all you continue to do in healthcare!

  • cardiology emr

    6/22/2010 1:08:33 AM |

    Thank you so much for the advice I will try having an supplement calcium, to preserve bone health and reduce blood pressure for my own good.

    mjd

  • Anonymous

    6/22/2010 2:09:39 AM |

    interesting. So does this mean that those areas where the calcium levels in drinking water are high : "hard" or "temporary hard", are areas where high vitamin D could work against residents trying to maintain healthy arteries?

    Trevor

  • Anonymous

    6/22/2010 5:02:05 AM |

    I'm 37 and have been taking 6,000 i.u. of vitamin D per day for the last several months.  I started urinating blood last night and have a CT scan in a few days to see the likely cause of it all - kidney stones.

    My Dad also had them. I think the vitamin D may have contributed in bringing this about.

    Coincidently, I'd started taking Tums (rich in calcium) every now and then for heartburn about a month or two ago.  

    Timely post doc!

  • Anne

    6/22/2010 7:17:17 AM |

    Dear Dr Davis,

    Please can you quote the links to the studies you mention in this blog. I have both osteoporosis and a heart valve defect (bicuspid aortic valve) and calcification is being deposited on the aortic valve. My levels of 25(OH)D range from 60 to 100 ng/ml. I have my bone profile tested every time I have my 25(OH)D tested and so far my serum calcium levels have been in the normal range but your post worries me considerably.

    Anne

  • moblogs

    6/22/2010 9:03:29 AM |

    I would agree that we probably need no dairy based calcium at all, since it is only necessary at birth through mother's milk.
    Even so, I do like my dairy products in moderation so that's all I take - no additional calcium supplements; and my blood calcium level and bone density has benefited from just D on top.

  • steve

    6/22/2010 3:31:52 PM |

    while current blood levels of D3 may appear to be inadequate, there is no science to demonstrate what the higher levels shuld be.  While a blood level of 60 coming from the sun may be wonderful, there are no studies, let alone ones of any duration, that show that supplementing with large doses of D3 to get to a 60 level do not pose any negative health consequences.  As we have learned with other vitamin supplementation, more is not always better; adverse consequences can arise, and there is not always a way to detect them such as blood calcium levels.  Caution should be the watchword.

  • Steve

    6/22/2010 3:50:56 PM |

    Dr Davis, what is your opinion of the supplement MSM? Does vitamin D have an effect on this also?

    Steve

  • Anonymous

    6/22/2010 4:24:11 PM |

    Dr. Davis,

    Magnesium competes with calcium absorption, and therefore is crucial to keeping calcium levels at bay.

  • Peter

    6/22/2010 8:11:05 PM |

    I noticed that a study this week found a correlation between very high vitamin D levels and increased risk of pancreatic cancer.
    http://media-newswire.com/release_1121308.html

  • nightrite

    6/22/2010 9:53:05 PM |

    I too had trouble with kidney stones untill I began supplementing with magnesium.  I take 600mg of various forms of mag and no longer have any problems with kidney stones.  I also take 6000 units of D3 and 180 of K2.  I have not had my serum calcium checked but don't eat too much dairy.

  • Anonymous

    6/22/2010 10:19:44 PM |

    What about high phytic acid foods like the raw almonds and cocoa advocated here?  Don't those contain as much or more calcium binding phytic acid as wheat?  I eat very low carb and no dairy products whatsoever.  My indulgences have been raw hazelnuts and cocoa -- now I'm wondering if this has been damaging in some way.  My understanding is that serum calcium represents only 1% of body's calcium and that an ionized calcium test is more accurate.  My doc drew blood today to re-check my vitamin d status but would not check mineral status.

  • Anonymous

    6/22/2010 10:26:31 PM |

    Different take on the calcium for me.  When I develop a faint, "fluttery", tachycardia (up to about 142 for a 63-year-old, and I feel absolutely horrible) I take about 500 mg of calcium citrate with about 1000 mg of vitamin C (for absorption of the calcium) and the heart beat gets stronger and the rate comes down.  Sometimes I have to repeat.  I found only one internet reference to this phenomenon below:

    http://www.ithyroid.com/ca_and_mg.htm

    I do not have access to health care as I am one of the working poor.  Perhaps you can comment, Dr. Davis.  Thanks, Catherine

  • Dr. William Davis

    6/22/2010 10:30:07 PM |

    Hi, Jessica--

    I think that you and your group are managing the calcium/vit D issue the right way.

    Unfortunately, some people are wrongly interpreting this to mean that vitamin D causes hypercalcemia. It simply means that calcium is unnecessary when D is restored.

  • Dr. William Davis

    6/22/2010 10:31:32 PM |

    Jenny--

    Thanks for the clarification.

    Thankfully, your situation is the exception. Most people maintain normal calcium levels even while consuming dairy and other calcium-rich foods.

    Several responders here make the point about magnesium, which I agree with. Have you addressed magnesium? Magnesium deficiency is exceptionally common, since it has been taken out of most drinking water.

  • Anonymous

    6/23/2010 2:29:29 AM |

    I noticed that a study this week found a correlation between very high vitamin D levels and increased risk of pancreatic cancer.

    Cited are NOT very high levels! The claim is higher rates of pancreatic cancers with >100 nmol/ml - which translates into 40 ng/ml, a level considerably lower than the one recommended here by Dr. Davis (~60-70 ng/ml if I remember correctly). Another claim is NO difference in rates of several other cancers across a large range of 25(OH)D concentrations.

  • LeonRover

    6/23/2010 9:11:25 AM |

    Peter's comment above led me to read the newswire report referred to.

    This study was trying to establish any epidemiological association of increased levels of Vit D with reduced incidences of various cancers. No such associations were observed. Rather in the case of pancreatic cancer only, it was observed that when the  level of Vitamin D was GREATER than 100 nmol per litre, there was higher incidence of this disease. Another way of looking at this observation is that at levels below 100 nmol per litre there was no association of pancreatic cancer with levels of Vit D LOWER than 100 nmol per litre.

    As far as cancers are concerned there is no point in considering Vit D status as long as it below 100 nmol per litre.

  • Mike

    6/23/2010 10:07:09 PM |

    This is timely. I just had blood work done recently and my Dr.'s staff ordered the wrong test. Instead of measuring D3, they measured D2 calcitriol. I don't know what to make of the result: 120.8 pg/mL on a scale of 10.0-75.0. It's extremely high.  The last time I had my vitamin D3 tested, it was 59.2 ng/mL on a scale of 32-100.
    FWIW, I follow a low carbohydrate Paleo diet and consume very little dairy. I do take a multivitamin 3-5 days per week, but it only provides 300 mg of calcium (along with 210 mg of magnesium). I also take 500 mg of magnesium citrate every evening.
    I'd sure like to know what to make of this.

  • TedHutchinson

    6/24/2010 7:54:39 AM |

    @ LeonRover
    The information on pancreatic cancer & vitamin D status comes from Finland

    The further from the equator the greater the swing from high to low status. To have a good shower requires tight regulation of both hot and cold water supplies and a reserve store of both hot and cold supply so neither ever runs out.

    Vieth explains in this paper.
    How to Optimize Vitamin D Supplementation to Prevent Cancer

    In the same way fluctuating concentrations of 25(OH)D may also be a problem, Regions at high latitude or with low environmental
    ultraviolet light can be associated with the greater risks reported for prostate and pancreatic cancers. At temperate latitudes, higher summertime 25(OH)D levels are followed by sharper declines in 25(OH)D, causing inappropriately low 1-hydroxylase and high 24-hydroxylase, resulting in tissue 1,25(OH)2D below its ideal set-point.
    The answer is to keep levels BOTH HIGH and STABLE.
    Humans only build a stored reserve of D3 in tissue above 40ng/ml = 100nmol/l. Only around 60ng/ml are there sufficient D3 reserves for lactating mothers to pass to babies in breast milk. At latitude 32 it takes modern women 6400iu/daily/D3 to provide naturally replete vitamin D breast milk.

  • Mike

    6/24/2010 8:30:44 PM |

    Thanks Ted. That clarifies the role of calcitriol, but I am still wondering why my level measured so high, if even transiently.

  • Anonymous

    6/24/2010 8:37:38 PM |

    I'm anonymous from above who talked about kidney stones and blood in my urine.

    I had the CT scan done yesterday. I have stones, one of them a whopping 1.4 cm.  

    Be careful people.

  • Catherine

    6/25/2010 10:07:09 PM |

    (I am a different Catherine than the one above with tachycardia)

    For years because I had osteopenia, I was advised to take loads of calcium.  Later they told us to add vitamin D with it.  I am now FULL of calcium deposits all over my body.

    A year ago, Dr. Davis advised me to try magnesium for a bad arrhythmia problem, and it not only quickly cured my arrhythmia, insomnia, and RLS, but I have much less grinding sounds and arthritis pain. I was the poster girl for magnesium deficiency and no one except Dr. Davis even mentioned trying it.

    I think along with K2, magnesium is of upmost importance to balance the D and calcium. I only take 500 mg a day now since I don't consume dairy, but after this article, I may totally stop supplementing any calcium and let the K2 and magnesium perhaps reduce some of the deposits..

  • Anonymous

    6/27/2010 12:24:40 AM |

    @Mike -- I have the same issue/question.  My 25 OH was 62 but the 125 test was sky high.  My serium calcium was normal.  I wonder if Holick's new book gives detailed info on how to interpret lab tests.  His first book just said that the correcxt test is the 25 OH but didn't explain if there is any danger is a sky high 125.

  • Crystal

    7/4/2010 6:44:07 AM |

    This is an awesome post. Great post. Thanks for sharing this. Looking forward to read more from you.
    Green Tea

  • josephmoss

    7/29/2010 5:35:01 AM |

    Vitamin D3:

    NOW Vitamin D softgels supply this key vitamin in a highly-absorbable liquid softgel form. Vitamin D is normally obtained from the diet or produced by the skin from the ultraviolet energy of the sun. However, it is not abundant in food. As more people avoid sun exposure, Vitamin D supplementation becomes even more necessary to ensure that your body receives an adequate supply. Vitamin D3 on discount at NutroVita.com.

    For more details please visit:
    http://www.nutrovita.com/32760/now-foods/vitamin-d-3-2-000-iu.htm

  • TedHutchinson

    7/29/2010 9:09:26 AM |

    UK readers need to be aware that estimated shipping cost to UK from Nutrovita = $26.50
    whereas
    Item cost IHERB= $4.96 + International Airmail = $4.00
    If you haven't used IHERB before code WAB666 saves $5.
    Remember UK customs apply VAT on orders £18 and above + UK PO charge £8 handling fee so I make orders up to around £17.50 before shipping to avoid that happening.
    To use GOOGLE toolbar to convert currency enter
    4.96 USD in GBP

  • Anonymous

    12/27/2010 7:27:18 PM |

    Dr. Davis,
    Since increasing my Vitamin D, Magesium and Melatonin I suddenly have very brittle, splitting fingernails.  Any idea which if any of these caused this?  Any suggestions?
    Thanks

    Love your blog!!!!!

  • Jack

    3/4/2011 4:13:40 PM |

    Chances are the calcium supplement you are taking now is a rock source of calcium. The label will say "calcium carbonate", which is nothing more than limestone. AlgaeCal Plus contains an organic, plant-sourced calcium form derived from a unique South American marine algae called Algas Calcareasâ„¢.

  • Emr reviews

    4/2/2011 12:01:36 AM |

    think one of the greatest hurdles is overcoming misconceptions in the minds of regulators, doctors and patients alike. I just returned from a trip to Germany and colleagues there are amused about America's 3rd World-like medical records situation

  • Anonymous

    4/2/2011 8:43:46 PM |

    I have celiac disease and osteopenia in my spine and no bone loss in my hips. I have a strong family history of osteoporosis as well.

    Because my calcium intake is less than or equal to 500 mg I take:

    600 mg calcium citrate at two seperate meals

    1200 IU's D3

    500 mg magnesium citrate

    I track using fitday. I'm grain, legume, dairy, sugar and processed food free and follow a paleo type dietary plan.

    Is this okay?

  • Anonymous

    4/2/2011 11:04:23 PM |

    I meant:

    600 mg calcium citrate in total but dosage is split between two seperate meals.

  • Dave

    5/2/2011 11:25:59 PM |

    I've seen research that shows the body produces more MGP and other calcium handling proteins with higher doses of Vitamin D.  You would expect this effect as a evolutionary collaboration with Vitamin D activity.  Higher doses of Vitamin K2 are needed to carboxylate these proteins and make them active.  These proteins are active in various places in the body like the arteries and the kidneys.  I have a theory that taking Vitamin K2 helps prevent kidney stones and maybe gallbladder stones of the calcium type.

    Uncarboxylated MGP is actually worse than the fully carboxylated MGP.  Guinea pigs are given cholesterol and high levels of Vitamin D in research to give them artery disease by exceeding their Vitamin K2 levels thus creating low carboxylation levels.

    More Vitamin K2 may well be good for those kidney stones.

  • Dave

    5/3/2011 12:14:43 AM |

    There is recent and startling Dutch research to the point that Vitamin K2 is specifically used to carboxylate calcium handling proteins that remove calcium from the arteries and promote heart health.  If you are taking extra Vitamin D, the body also generates more of these calcium handling proteins so the need for Vitamin K2 also increases.

    I had good experience over six months with taking Vitamin K2 and found my running speed increased by 8% and the itching or other mild, variable sensations in my chest have decreased 98%.  I suspect this is connected to reduction of calcification.  I noticed a reduction in my symptoms after six weeks.

    My Vitamin K2 has:
      1300 mcg Vitamin K2, Mk-4
       100 mcg Vitamin K2, MK-7
      1000 mcg Vitamin K (the ordinary stuff)

  • Reikime

    9/22/2011 2:02:34 AM |

    Reading all these posts I used to think of vitamin D and magnesium and K2 the same a most posters. Intuitively never took calcium, was up to 6000 mg of D3/ day to achieve a level of 43- up from 26.

    That said, my serum calcium has trended upward to 10.3. I am now having a few blood tests to check  for hyperparathyroidism!  The foremost parathyroid doc in the USA is Dr. James Norman from Tampa, and his website is very informative and puts a different spin on what I thought I knew of these matters. Parathyroids is ALL he and his 2 colleagues do all day every day. Please give this a look to be fully informed on the matter of Vitamin D supplementation.       www.parathyroid.com
    I have no connection, but if I find out I have an adenoma on one of my parathyroids, this is where I will have it removed!
    Jeanne ( RN,BSN)

  • Reikime

    9/22/2011 2:05:44 AM |

    Oops,  meant to add I have also supplemented with 400-800mg of magnesium and 1 Life Extension K2 in addition to the Vitamin D for several years.

    Reikime

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