Restaurant eating: A fructose landmine

There is no remaining question that fructose is among the worst possible things humans can consume.

Followers of the Heart Scan Blog already know this, from conversations like The LDL-Fructose Disconnect, Where do you find fructose?, and Goodbye, fructose.

But fructose, usually as either high-fructose corn syrup (44%, 55%, occasionally higher percentage fructose) or sucrose (50% fructose), is ubiquitous. I've seen it in the most improbable places, including cole slaw, mustard, and dill pickles.

It's reasonably straightforward to avoid or minimize fructose exposure while eating at home, provided you check labels and focus on foods that don't require labels (like green peppers, salmon, and olive oil, i.e., unprocessed foods). But when you choose to eat at a restaurant, then all hell can break loose and fructose exposure can explode.

So what are some common and unsuspected fructose sources when eating at a restaurant?

Salad dressings--Dressings in all stripes and flavors are now made with high-fructose corn syrup and/or sucrose. This is especially true of low-fat, non-fat, or "lite" dressings, meaning oils have been replaced by high-fructose corn syrup. It can also be true of traditional non-low-fat dressings, too, since high-fructose corn syrup is just plain cheap.

Olive oil and vinegar are still your safest bets. I will often use salsa as a dressing, which works well.

Sauces and gravies--Not only can sauces be thickened with cornstarch, many pre-mixed sauces are also made with high-fructose corn syrup or sweetened with sucrose. Barbecue sauce is a particular landmine, since it is now a rare barbecue sauce not made with high-fructose corn syrup as the first or second ingredient. Sauces for dipping are nearly always high-fructose corn syrup-based.

Ketchup--Yup. Good old ketchup even is now made with high-fructose corn syrup. In fact, you should be suspicious of any condiment.

Highball, Bloody Mary, Margarita, Daiquiri, beer--Even the before-dinner or dinner drink can have plenty of fructose, particularly if a mix is used to make it. While Blood Marys seem the most benign of all, adorned with celery, pickle, and olive, just take a look at the ingredient label on the mix used: high-fructose corn syrup.

Fructose is a stealth poison: It doesn't immediately increase blood sugar; it doesn't trigger any perceptible effect like increased energy or sleepiness. But it is responsible for an incredible amount of the health struggles in the U.S., from obesity, to diabetes, to hyperlipidemias and heart disease, to arthritis, to cataracts.

A glycation rock and a hard place

Advanced Glycation End-products, or AGEs, the stuff of aging that mucks up brains, kidneys, and arteries, develop via two different routes: endogenous (from within the body) and exogenous (from outside the body).

Endogenous AGEs develop via glycation. Glycation of proteins in the body occurs when there are glucose excursions above normal. For instance, a blood glucose of 150 mg/dl after your bowl of stone-ground oatmeal causes glycation of proteins left and right, from the proteins in the lens of your eyes (cataracts), to the proteins in your kidneys (proteinuria and kidney dysfunction), to skin cells (wrinkles), to cartilage (brittle cartilage followed by arthritis), to LDL particles, especially small LDL particles (atherosclerosis).

At what blood sugar level does glycation occur? It occurs even at "normal" glucose levels below 100 mg/dl (with measurable long-term cardiovascular effects as low as 83 mg/dl). In other words, some level of glycation proceeds even at blood glucose levels regarded as normal.

There's nothing we can do about the low-level of glycation that occurs at low blood sugar levels of, say, 90 mg/dl or less. However, we can indeed do a lot to not allow glycation to proceed more rapidly, as it inevitably will at blood sugar levels higher than 90 mg/dl.

How do you keep blood sugars below 90 mg/dl to prevent excessive glycation? Avoid or minimize the foods that cause such rises in blood sugar: carbohydrates.

What food increases blood sugar higher than nearly all other known foods? Wheat.

Is einkorn the answer?

People ask: "What if I would like a piece of bread or other baked product just once in a while? What is safe?"

Eli Rogosa, Director of The Heritage Wheat Conservancy, believes that a return to the wheat of our ancestors in the Fertile Crescent, circa 10,000 years ago, is the answer.

Former science teacher, now organic farmer, farm researcher, and advocate of sustainable agriculture, Eli has been reviving "heritage" crops farmed under organic conditions, some of her research USDA-funded.

In particular, Eli has been cultivating original 14-chromosome ("diploid") einkorn wheat. Although einkorn contains gluten (in lesser quantities despite the higher total protein content), the group of proteins that trigger the immune abnormalities of celiac disease and other immune phenomena, Eli tells me that she has witnessed many people with a variety of wheat intolerances, including celiac disease, tolerate foods made with einkorn wheat. (The variety of glutens in einkorn differ from the glutens of the dwarf mutant that now dominate supermarket shelves.)

Eli travels to Israel every year, returning with "heritage" seeds for wheat and other crops. She formerly worked in the Israel GenBank as Director of the Ancient Wheat Program. She has written a brochure that describes her einkorn wheat.

Eli sent me 2 lb of her einkorn grain that nutritionist, Margaret Pfeiffer, and I ground into bread. Our experience is detailed here. My subsequent blood sugar misadventure, comparing einkorn bread to conventional organic whole wheat bread is detailed here, followed by the odd neurologic effects I experienced here.

Anyone else wishing to try this little ancient wheat experiment with einkorn can also obtain either the unground grain or ground flour through Eli's website, www.growseed.org. Most recently, einkorn pasta is being retailed under the Jovial brand at Whole Foods Market.

If anyone else makes bread or any other food with Eli's einkorn wheat, please let me know:

1) Your blood sugar response (before and 1 hour after consumption)
2) Whether you experienced any evidence of wheat intolerance similar to what you experienced with conventional wheat, e.g., rash, acid reflux, gas and cramping, moodiness, asthma, etc.

But remember: Wheat effects or no, einkorn is still a grain. My belief is that humans do best with little or no grain. The einkorn experience is an effort to identify reasonable compromises so that you and I can have a piece of birthday cake once a year without getting sick.

Genetic incompatibility

Peter has lipoprotein(a), or Lp(a), a genetic pattern shared by 11% of Americans.

It means that Peter inherited a gene that codes for a protein, called apoprotein(a), that attaches to LDL particles, forming the combined particle Lp(a). It also means that his overall pattern responds well to a high-fat, high-protein, low-carbohydrate diet: The small LDL particles that accompany Lp(a) over 90% of the time are reduced, Lp(a) itself is modestly reduced, other abnormalities like high triglycerides (that facilitate Lp(a)'s adverse effects) are corrected. Small LDL particles are, by the way, part of the genetic "package" of Lp(a) in most carriers.

Peter also has another gene for Apo E4, another genetically-determined pattern shared by 19% of Americans. (Another 2% of Americans have two "doses" of Apo E4, i.e., they are homozygotes for E4.) This means that the Apo E protein, normally responsible for liver uptake and disposal of lipoproteins (especially VLDL), is defective. In people with Apo E4, the higher the fat intake, the more LDL particles accumulate. (The explanation for this effect is not entirely clear, but it may represent excessive defective Apo E-enriched VLDL that competes with LDL for liver uptake.) People with Apo E4 therefore drop LDL (and LDL particle number and apoprotein B) with reductions in fat intake.

This is a genetic rock-and-a-hard-place, or what I call a genetic incompatibility. If Peter increases fat and reduces carbohydrates to reduce Lp(a)/small LDL, then LDL measures like LDL particle number, apoprotein B, and LDL cholesterol will increase. Paradoxically, sometimes small LDL particles will even increase in some genetically predisposed people.

If Peter decreases fat and increases carbohydrates, LDL particle number, apoprotein B, and LDL cholesterol will decrease, but the proportion of small LDL will increase and Lp(a) may increase.

Thankfully, such "genetic incompatibilities" are uncommon. In my large practice, for instance, I have about 5 such people.

The message: If you witness paradoxic responses that don't make sense or follow the usual pattern, e.g., reductions in LDL particle number, apoprotein B, and small LDL with reductions in their dietary triggers (i.e., carbohydrates, especially wheat), then consider a competing genetic trait such as Apo E4.

The folly of an RDA for vitamin D

Tom is a 50-year old, 198-lb white male. At the start, his 25-hydroxy vitamin D level was 28.8 ng/ml in July. Tom supplements vitamin D, 2000 units per day, in gelcap form. Six months later in January (winter), Tom's 25-hydroxy vitamin D level: 67.4 ng/ml.

Jerry is another 50-year old white male with similar build and weight. Jerry's starting summer 25-hydroxy vitamin D level: 26.4 ng/ml. Jerry takes 12,000 units vitamin D per day, also in gelcap form. In winter, six months later, Jerry's 25-hydroxy vitamin D level: 63.2 ng/ml.

Two men, similar builds, similar body weight, both Caucasian, similar starting levels of 25-hydroxy vitamin D. Yet they have markedly different needs for vitamin D dose to achieve a similar level of 25-hydroxy vitamin D. Why?

It's unlikely to be due to variation in vitamin D supplement preparations, since I monitor vitamin D levels at least every 6 months and, even with changes in preparations, dose needs remain fairly constant.

The differences in this situation are likely genetically-determined. To my knowledge, however, the precise means by which genetic variation accounts for it has not been worked out.

This highlights the folly of specifying a one-size-fits-all Recommended Daily Allowance (RDA) for vitamin D. The variation in need can be incredible. While needs are partly determined by body size and proportion body fat (the bigger you are, the more you need), I've also seen 105 lb women require 14,000 units and 320-lb men require 1000 units to achieve the same level of 25-hydroxy vitamin D.

An RDA for everyone? Ridiculous. Vitamin D is an individual issue that must be addressed on a person-by-person basis.

Heart scan: Standard of care?

If coronary disease is easy to detect by measuring coronary calcium, shouldn't this represent the standard of care?

In other words, if you've been seeing your doctor and he/she has been monitoring cholesterol levels and, inevitably, talks about statin drugs, then you have a heart attack, unstable angina, or die--yet never knew you had heart disease--isn't this negligence?

Coronary calcium, and thereby coronary atherosclerotic plaque, are markers for the disease itself. Unlike cholesterol, high blood pressure, etc., that represent risk factors for coronary atherosclerotic plaque, coronary calcium is a measure of total plaque: "soft" elements like lipid collections, necrotic tissue, fibrous tissue, as well as "hard" elements like calcium. Because calcium occupies 20% of total atherosclerotic plaque volume, it can be used as an indirect "dipstick" for total plaque.

So why isn't an unexpected heart attack, hospitalization for unstable heart symptions, emergency bypass, etc., not regarded as potential malpractice? These are not benign events, but potentially life-threatening.

The costs of doing drug business?

Here's a telling situation.

Liz had been on prescription niacin, Niaspan, 1500 mg per day (3 x 500 mg tablets) for several years to treat her severe small LDL pattern and familial hypertriglyceridemia (triglycerides 500-1000 mg/dl). Because her health insurance had been paying for the "drug," she insisted on taking the prescription form.

A change in insurance, however, meant that the Niaspan was no longer covered. Her pharmacy wanted to charge $227 per month.

Liz came to the office in tears, worried that she was going to have to choke up $227 per month. I reminded her that, as I had told her several years ago, she could easily replace the Niaspan with over-the-counter Sloniacin or Enduracin. Both release niacin over approximately 6 hours, just like Niaspan.

Here are the prices I've seen with Sloniacin, 100 tablets of 500 mg:

Walgreens: $15.99
Walmart: $12.99
Costco: $8.99

So the most expensive source, Walgreens, would cost Liz just under $15.99 per month to take 1500 mg per day.

$15.99 versus $227.00 per month for preparations that are highly similar. Hmmmmmm.

I wonder what the $211.01 extra per month goes towards? Admittedly, Abbott Labs, the current company selling Niaspan (after Abbott acquired Kos), has invested in a few clinical trials, such as ARBITER-HALTS6. But does supporting research justify this much difference, a difference that amounts to $2532 over a year? If just 100,000 patients are prescribed Niaspan at this dose (a typical dose), this generates $253 million.

Is the cost of developing and marketing a supplement-turned-drug that great? Is this justifiable? Is it any wonder that our health insurance premiums continue to balloon?

I use Sloniacin and Enduracin almost exclusively.

Measurement

A crucial component of self-empowerment in healthcare is to be able to measure various health parameters. More and more measurement tools are entering the direct-to-consumer arena.

Quantification of various phenomena is important in managing many aspects of health. Imagine a carpenter trying to build a house without the use of a tape measure, level, or other measuring tools. In health, as in building a house, measurement, adjustment, and correction are critical.

Among the most helpful health measurement tools:

Blood glucose meters--Blood glucose meters aren't just for diabetics. They are among the most powerful weight loss tools available.

Blood pressure cuffs--There's no better way to assess blood pressure than to assess it under all the varied conditions of life: When you're tired, when you're excited, when you're upset, when you're happy, hungry, stomach full, morning, night. This is a lot better than the one isolated measure in the doctor's office.

Digital thermometers--Your first a.m. oral temperature is a great way to assess thyroid status. We aim to maintain first a.m. oral temperature around 97.3 degrees F, the normal human temperature upon arising that reflects normal thyroid function. (No, Dr. Broda Barnes fans, axillary temperatures should NOT be used due to flagrant variation from right armpit to left armpit, modifying effects of clothing and ambient temperature, etc. Oral temperature tracks internal, "core," temperature fluctuations reliably, including circadian variation, far better than axillary temperatures.)

Fingerstick blood tests--An incredible number of blood tests are now available just by performing a simple fingerstick in your kitchen or bathroom. You can get 25-hydroxy vitamin D, lipids, thyroid measures (TSH, free T3, free T4), hormones (DHEA, testosterone, estrogens). And the list is growing rapidly. Salivary tests are also growing in number for many of the same measures.

A variation on fingerstick blood tests are devices like CardioChek that allow you to do a fingerstick, but also run the test on your own device at home. (The CardioChek device tests total cholesterol, triglycerides, and HDL.)

Urine pH--You can dipstick your own urine to assess the relative acidity or alkalinity of your lifestyle. Acid pH (7 or below) suggests that diet is weighed too heavily in favor of animal products and grains. An alkaline pH (above 7) suggests plentiful vegetables and fruits, not counteracted by animal products and grains.

There are many more, including the ZEO device to monitor sleep quality, RESPeRATE for reduction of blood pressure, HeartMath to manage stress and augment the parasympathatic (relaxation) response. We've come a long way compared to the health monitoring devices of just 25-30 years ago.

Anyway, that's a partial list. Given the rapid advances in technology that allow such home tests, I anticipate a much longer list in the coming few years.

For some perspective on how far these devices have come, here's a great graphic of an early sphygmomanometer, or blood pressure gauge.


Courtesy Wellcome Library, London

I lost 37 lbs with a fingerstick

Jack needed to lose weight.

At 5 ft 7 inches, he weighed in at 273 lbs, putting his BMI at a sobering 42.8. (A BMI of 30 or above is classified as "obese.") In addition to lipoprotein(a), Jack had an extravagant quantity of small LDL (the evil "partner" of lipoprotein(a)), high triglycerides, and blood sugars in the diabetic range. With a heart scan score of 1670, Jack had little room for compromises.

Try as he might, Jack could simply not stick to the diet I urged him to follow. Three days, for instance, of avoiding wheat was promptly interrupted by his wife's tempting him with a nice BLT sandwich. This triggered his appetite, with diet spiraling downward in short order.

So I taught Jack how to check his blood sugars using a fingerstick device, what I call the most important weight loss tool available. I asked Jack to check his pre-meal blood glucose and his one-hour after-meal blood glucose and not allow the after-meal blood glucose to rise any higher than the pre-meal. For example, if blood glucose pre-meal was 115 mg/dl, after-meal blood glucose should be no higher than 115 mg/dl.

If any food or combination of foods increase blood glucose more than the pre-meal value, then eliminate the culprit food or reduce the portion size. For example, if dinner consists of baked salmon, asparagus, and mashed potatoes, and pre-meal blood glucose is 115 mg/dl, post-meal 155 mg/dl, reduce or eliminate the mashed potatoes. If slow-cooked, stone ground oatmeal causes blood glucose to increase from 115 mg/dl to 185 mg/dl (a typical response to oatmeal), then eliminate it.

Having immediate feedback on the effects of various foods finally did it for Jack: It identified foods that were triggering excessive blood sugar rises (and thereby insulin) and foods that did not.

What Jack did not do is limit or restrict calories. In fact, I asked him to eat portion sizes that left him comfortable. There was no need to reduce calories, push the plate away, etc. Just don't allow blood sugars to rise.

Six months later, Jack came back 37 lbs lighter. And he got there without calorie-counting, without regulating portion sizes, without hunger.

The two kinds of small LDL

You won't find this in any publication nor description (at least ones that I've come across) about the ubiquitous small LDL particles. It's an observation I've made having obtained thousands of advanced lipoprotein panels of the sort that break lipoproteins down by size. I've discussed this issue previously here. But small LDL is so ubiquitous, not addressed by conventional strategies like statin drugs or fat restriction (it is made worse, in fact, by reducing fat in the diet), that it is worth keeping at the top of everyone's consciousness.

(Because most of the lipoprotein analyses performed in my office are done via NMR, I will discuss in terms relevant to NMR. This does not necessarily mean that similar observations cannot be made with centrifugation, i.e, VAP from Atherotech, or gel electropheresis from Berkeley, Boston Heart Lab, Spectracell, and others).

There are two basic varieties of small LDL particles:

1) Genetically-programmed--e.g., via cholesteryl-ester transfer protein (CETP) activity
2) Acquired--via carbohydrate consumption


It means that people with acquired small LDL from carbohydrate consumption can reduce small LDL to zero with reduction of carbohydrates, especially the most small LDL-provoking foods of all: wheat, cornstarch, and sucrose.

It also means that people who have small LDL for genetically-determined reasons can only minimize, not eliminate, small LDL. By NMR, we struggle to keep small LDL in the 300-600 nmol/L range when genetically-determined. (People typically start with 1400-3000 nmol/L small LDL particles prior to diet changes and other efforts.) We can only presumptively identify genetically-determined small LDL when all the appropriate efforts have been made, including reduction in weight to ideal, yet small LDL persists.

Here is where we need better tools: when you've done everything possible, yet small LDL persists.

While we break LDL particles (NOT LDL cholesterol, the crude and misleading way of viewing atherosclerosis causation) down by size, it's really about all the undesirable characteristics that accompany small size:

--Distortion of Apo B conformation--i.e., the primary protein that directs LDL particle fate is distorted, making it less likely to be cleared by the liver but more likely to be taken up by inflammatory (macrophages) in the artery wall, creating plaque. It means that small LDL particles linger for a longer time than larger particles.

--Small LDLs are more oxidation-prone. Oxidized LDL are more avidly taken up by inflammatory macrophages.

--Small LDLs are more glycation-prone.

--Small LDLs are more adherent to structural tissues, e.g., glycosaminoglycans, that reside in the artery wall.

You and I cannot measure such phenomena, so we resort to distinguishing LDL particles by size.

The drug industry believes it may have a solution to small LDL in the form of CETP-inhibiting drugs, like anacetrapib. In the way of nutritional solutions beyond carbohydrate reduction, weight loss/exercise, niacin, vitamin D normalization, and omega-3 fatty acid supplementation, there are exciting but very preliminary data surrounding the possibility that anthocyanins may inhibit CETP activity. Having toyed with this concept for the past 6 months, I remain uncertain how meaningful the effect truly is, but it is harmless, since we obtain anthocyanins from foods colored purple or purplish, such as blackberries, blueberries, cherries, red leaf lettuce, red cabbage, etc.

I welcome any unique observations on this issue.
Life Extension article on vitamin D

Life Extension article on vitamin D


For anyone looking for a discussion about the emerging role of vitamin D as a cause for coronary disease, see my recent article, Vitamin D’s Crucial Role in Cardiovascular Protection, in Life Extension Magazine, now posted online at:

http://www.lef.org/magazine/mag2007/sep2007_report_vitamind_01.htm.




Vitamin D has assumed an absolutely critical role in the Track Your Plaque program for coronary plaque reversal and dropping CT heart scan scores. Since adding vitamin D and aiming for blood levels of 50-60 ng/ml, our success rate has skyrocketed. In fact, I wonder just how well our two most recent record holders--51% and 63% drops in heart scan scores--would have fared without it. (They probably would have dropped, but no where near as much.)

Also, a full-length booklet that contains just about everything you want to know about vitamin D (or at least a right-this-moment summary of what is known about it) will be available to Track Your Plaque Members for free before the end of the year.

If you haven't done so already, DO THE D!!

Comments (5) -

  • wccaguy

    9/14/2007 5:24:00 AM |

    Dr. Davis,

    I continue to be amazed at how much value you are providing all the time to those of us deeply concerned about heart disease.

    Whether it's at this blog, at LEF.org, at your TrackYourPlaque.com site, or in your Track Your Plaque book, your contribution is pretty astounding.

    I only found your work in the last 2-3 weeks and already it has made a deep impression on me and I'm getting clearer about what I need to do to combat heart disease in myself and in family members.

    Thanks for all you're doing!

  • Dr. Davis

    9/14/2007 12:14:00 PM |

    Wow!

    Thanks for the feedback. I'm glad it's helping you. It is wonderful to hear back about the impact the program is having.

  • Bix

    9/15/2007 9:45:00 AM |

    Excellent article!  I especially liked the tie-in to poor kidney function.

  • Rich

    9/17/2007 1:14:00 AM |

    Dr. Davis: In your excellent LEF article, I found your reference to a fascinating statement about statins and vitamin D by Dr. David Grimes of the UK. For those interested, here is the Lancet source article (reprinting for educational purposes):

    The Lancet 2006; 368:83-86
    DOI:10.1016/S0140-6736(06)68971-X

    Are statins analogues of vitamin D?
    David S Grimes MD, Blackburn Royal Infirmary, Blackburn, Lancashire BB6 8HE, UK

    Summary

    There are many reasons why the dietary-heart-cholesterol hypothesis should be questioned, and why statins might be acting in some other way to reduce the risk of coronary heart disease. Here, I propose that rather than being cholesterol-lowering drugs per se, statins act as vitamin D analogues, and explain why. This proposition is based on published observations that the unexpected and unexplained clinical benefits produced by statins have also been shown to be properties of vitamin D. It seems likely that statins activate vitamin D receptors.
    Back to top

    During the late 19th century, conventional wisdom held that masturbation was the cause of epilepsy, a more plausible explanation than the previous notion that epilepsy was the result of possession by the devil, and illness in general the result of divine interference. Since bromide was thought to reduce sexual desire, it became the logical treatment. Although reasonably successful, bromide worked for reasons that are different from the theory on which it was based. Can the same be said of statins for heart disease?

    The emergence of coronary heart disease (CHD) in the 20th century required an explanation. Some had noted that cholesterol accumulated in the walls of the arteries, and a process of accretion was hence described as the major mechanism. Cholesterol was assumed to originate from diet, and the diet-cholesterol-heart hypothesis was established. The logical treatment was to reduce dietary and serum cholesterol concentrations.

    Many inconsistencies in this hypothesis have emerged and been disregarded. In the London banking and transport study,1 for example, men with the highest dietary cholesterol intake had the lowest incidence of CHD. Furthermore, the results of the Framingham study2 showed that raised concentrations of serum cholesterol were predictive of CHD only in men younger than age 55 years. Findings of studies from Honolulu3 and Paris4 suggest a protective effect of high serum cholesterol concentrations, and the Leningrad paradox5 indicates that those exposed to famine subsequently have a high incidence of CHD, the opposite of what is expected. In Europe, populations that consume a large amount of dietary fat and cholesterol have a low incidence of CHD (the French paradox),6 and the lowest incidence of CHD is seen in European nations with the lowest consumption of wine and the most socioeconomic deprivation (the Albanian paradox).7

    Initial treatments to reduce serum cholesterol were not effective. When introduced, however, statins did greatly reduce serum cholesterol concentrations by interfering with its synthesis; the beneficial effects of statins in CHD have been assumed to be the result of cholesterol-lowering, an assumption that I believe is a serious mistake.

    Statins and the heart

    The first statin trial was the Scandinavian Simvastatin Survival Study (4S),8 and its findings indicated a significant clinical benefit from simvastatin. The results of the West of Scotland Coronary Prevention Study (WOSCOPS)9 also showed clinical benefit from statins (pravastatin) and of a greater magnitude than expected; the mortality reduction was about 35%, whereas the reduction in cholesterol concentrations predicted a mortality reduction of only 25%. WOSCOPS9 showed no association between cholesterol-lowering and clinical benefit,10 indicating that cholesterol-lowering was not the mechanism by which pravastatin reduced coronary events.

    In WOSCOPS, statins lowered serum cholesterol concentrations, but also raised concentrations of HDL cholesterol and lowered those of serum triglyceride, indicating that inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase was not the only metabolic action. The clinical experiment of cholesterol-lowering was thus intrinsically flawed, and what must be understood is that 4S and WOSCOPS were trials of statin therapy and not trials of cholesterol-lowering.

    Unexpected benefits of statins

    It is noteworthy that the participants treated with pravastatin in WOSCOPS had a reduced incidence of diabetes compared with controls.11 Additionally, when pravastatin was given to recipients of heart transplants in an attempt to reduce the likelihood of CHD, a reduction in the rate of rejection and an increase in overall survival was noted, irrespective of CHD status.12 The same pattern was seen in recipients of kidney transplants.13 Clinical benefits of statins have also been noted in a placebo-controlled trial14 of atorvastatin for rheumatoid arthritis. Furthermore, simvastatin has been used successfully to treat patients with multiple sclerosis.15 As with CHD, diabetes, rheumatoid arthritis, and transplant rejection, the benefit noted with respect to multiple sclerosis is independent of any effect on serum cholesterol.
    Statins also have an effect on bone, and women who take statins have a greater bone density than those who do not.16 Moreover, the findings of the 10-year follow-up study of participants in 4S17 indicate a significantly reduced risk of cancer, particularly colorectal, lung, and prostate cancer, in those who received simvastatin. Results of a population study from Israel18 also show a greatly reduced risk of colorectal cancer in those taking statins.

    In 1974,19 a group of illustrious diet-cholesterol-heart researchers studied the association between cholesterol and cancer. They noted that high serum cholesterol concentrations conferred protection against colon cancer. The effects of statins mentioned above hence present a major paradox: how can a drug that lowers serum cholesterol concentrations reduce the risk of colon cancer when high serum cholesterol concentrations are, in fact, protective?

    A drug can act as a poison by blocking normal metabolic processes, but to produce a beneficial effect (other than antibacterial) we should assume that it is switching on or enhancing a normal metabolic process. I therefore suggest that statins mimic many of the actions of vitamin D and can be considered analogues of vitamin D.

    Sunlight and vitamin D

    Heart disease

    In Europe, there is a higher rate of mortality from CHD in the northern than in the southern countries, with the lowest rates noted along the Mediterranean coast.20 This pattern suggests that susceptibility to CHD is affected by duration of exposure to sunlight. This notion is supported by findings from the USA21,22 that the higher the altitude of residence, and hence the greater the sunlight intensity, the lower the risk of heart disease.

    Furthermore, the only dietary change that consistently protects against CHD is an increase in consumption of oily fish and fish oil, which contain large amounts of vitamin D.23 In the Netherlands, mortality from CHD was more than 50% lower in men who consumed at least 30 g of fish per day than in those who did not eat fish.24 A similar result was reported in women from a 16-year follow-up study in the USA.25

    Multiple sclerosis

    Multiple sclerosis also shows a latitude gradient in Europe, with the world's highest incidence reported in Scotland.26 The risk of developing the disease is reduced by a third by regular supplementation with vitamin D.27

    Cancer

    The risk of breast cancer and colon cancer is high in northwest Europe and much lower in the Mediterranean countries.28 And, in the UK, people die more readily from cancer in the north than in the south of the country. After being diagnosed, 34% of men with cancer and resident in Oxfordshire survive for 5 years compared with 26% of those who live in the northwest and Yorkshire. Men with stomach cancer who live in London survive on average twice as long as those who live in the northwest of England; the same applies to bladder cancer.29 Patients with colon cancer also have a greater chance of survival if they live in the south of England rather than in the north.30 The benefits of sunshine and vitamin D would explain these associations.
    Results of a study31 done in 1941 in the USA and Canada showed that the cancer death rates among residents of the most northern cities were two and a half times those of the most southern cities. An extensive study32 of more than 5000 locations in the USA has shown that incidence rates of cancer are lowest where ultraviolet light exposure is greatest. Bladder, breast, colon, kidney, oesophageal, ovarian, prostate, rectal, stomach, and uterine cancers, and non-Hodgkin lymphoma are associated with low exposure to ultraviolet light.32

    In the USA, cancer of the prostate has an increasing incidence with distance from the equator, suggesting a protective effect of sunshine. The incidence is highest in the eastern states and lowest in the west.33 This is exactly the same as with CHD, and is probably the result of a high altitude being protective because of greater ultraviolet light exposure. The association between prostate cancer and insufficient access to ultraviolet light has also been noted in the UK,34 with men exposed to low levels of ultraviolet light developing cancer at a younger age than those exposed to high levels (median age 67•7 years vs 72•1 years).

    In a study35 of 456 people with early-stage lung cancer who had undergone surgery, those diagnosed and operated on in the summer, spring, or autumn had a significantly higher 5-year survival rate than those diagnosed and operated on in the winter. The survival rate was 29% in those who took no vitamin D supplements and had treatment in the winter compared with 72% in those who took vitamin D supplements and were treated in the summer.35


    Diabetes

    The international distribution of diabetes in children is very similar to that of CHD, with incidence increasing with distance from the equator,36 again suggesting a protective effect of sunlight and vitamin D. Furthermore, children of women who do, compared with those who do not, take cod liver oil during pregnancy have a reduced incidence of type 1 diabetes.37 The findings of a retrospective study,38 undertaken in Finland and involving 10 821 children born in 1966, indicate that the incidence of diabetes in adulthood is almost ten times higher in those who do not, compared with those who do, take vitamin D supplements in childhood. The benefit of vitamin D supplementation during infancy has been further strengthened by the findings of a large study undertaken in Norway.39

    Rhematoid arthritis

    Kröger and colleagues40 noted that 16% of 143 women with rheumatoid arthritis, compared with the general population, had very low concentrations of serum calcidiol. During the winter, 73% had levels of calcitriol below the seasonally adjusted normal range and the lowest levels were in patients with very active disease. In another study,41 of 19 patients with rheumatoid arthritis given vitamin D supplements, nine reported a complete remission of symptoms, and eight a satisfactory response. Inflammatory markers also improved: the mean erythrocyte sedimentation rate fell by 43% and the mean concentrations of C-reactive protein by 52%. This study is a small one but although far from conclusive the results conform to a pattern that should not be ignored.


    Testing of my hypothesis

    In view of the above, there is a striking similarity between the benefits of vitamin D and the benefits of statin therapy. I believe that the unexpected and unexplained beneficial effects of statin therapy might be mediated by activation of vitamin D receptors by this group of drugs. This hypothesis is, in theory, easy to test.
    A prospective study should be undertaken in cancer treatment and prevention, with a factorial design, so that patients receive statins, vitamin D, a combination of statins and vitamin D, or placebo. A similar outcome in the three treatment groups would lend support to the suggestion of statins acting via vitamin D receptors. If vitamin D and statins are activating the same receptors, then if both are given in sub-maximum doses, the two together would have a greater effect than each individually. Intervention studies should also be undertaken to look at the relapse rates of established illnesses, including CHD, multiple sclerosis, and rheumatoid arthritis, comparing statins and vitamin D.

    The difficulty in doing these studies is that we know only the minimum dose of vitamin D necessary to prevent and heal rickets: we do not know the dose necessary to increase to a maximum the other effects, especially those that enhance immune competence. The same applies to statins: their effect on serum cholesterol concentrations is easy to measure, but we do not know what to measure as a biochemical surrogate for the other effects, again probably those enhancing immune competence. As such, a range of treatment doses of vitamin D and statins need to be investigated. Additionally, clinical trials of established treatments—eg, statins for CHD—are difficult to design because of the ethics of not giving an established medication (a statin), but in place a trial medication (vitamin D). Comparisons with vitamin D supplements could be undertaken, but only once the optimum dose of vitamin D has been established.

    Colonic mucosa and colonic cancer cells contain vitamin D receptors,42 strengthening my suggestion that vitamin D is biologically active in these tissues. Furthermore, vitamin D has an inhibitory effect on colonic carcinoma cell lines.43 Do statins have a similar effect? In-vitro experiments are one way that the effects of statins on vitamin D receptors could be investigated directly.

    Conclusion

    Anomalous results, such as the unexpected benefits of statins detailed here, lead to the advancement of science. Such an opportunity for research should not be overlooked. Statins should be looked at objectively and the diet-cholesterol-heart hypothesis on which the treatment was based disregarded. Statins have been described as wonder drugs because of their unexpected benefits; my hypothesis gives an opportunity for new thinking. The explanation of statins as analogues of vitamin D, if correct, would be reassuring to the millions of people who take them every day. Finally, sunlight and vitamin D might at last be recognised for their widespread health benefits.

    Conflict of interest statement
    I declare that I have no conflict of interest.


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    Affiliations

    a. Blackburn Royal Infirmary, Blackburn, Lancashire BB6 8HE, UK

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    Also, a full-length booklet that contains just about everything you want to know about vitamin D (or at least a right-this-moment summary of what is known about it) will be available to Track Your Plaque Members for free before the end of the year.

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