Grain Intake – and Cardiovascular Disease

Epidemiological studies have suggested that whole-grain intake is protectivefood_0320 against cancer, cardiovascular disease, diabetes and obesity. Just about every health care system worldwide recommends consuming three servings of whole grains daily.

Whole grains are rich in nutrients and phytochemicals; have high concentrations of dietary fibre, resistant starch, and oligosaccharides. Whole grains are rich in antioxidants including trace minerals and phenolic compounds and these compounds have been linked to disease prevention. Other protective compounds in whole grains include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. t1larg.gluten.foods.giAlthough it is difficult to separate the protective properties of whole grains from dietary fibre and other components, the disease protection seen from whole grains in prospective epidemiological studies far exceeds the protection from isolated nutrients and phytochemicals in whole grains.

So what is going wrong with the failure to prevent atherosclerotic cardiovascular disease (ASCVD)?

Despite all the preventative lifestyle and nutritional guidelines, ASCVD remains the biggest killer worldwide with the epidemic of vascular disease closely associated with diets predominantly carbohydrate based, including high intake of grains.  Confirming my personal experience as a non invasive preventative cardiologist for the past 20 years, I find it extremely hard to find truly healthy 50+ men or women. Published in Circulation 2011 it seems “ideal cardiovascular health” in healthy American 50+ men and women is equally impossibly hard to achieve despite the prevailing lifestyle wisdom and nutritional information available to all.  

Ideal CV Health  Circulation

In this study only 1/1000 “healthy individuals” (average age 57) achieved all 7 of the health behaviors and health factors.

  1. Non-smoking
  2. Body Mass Index < 25 m2/kg
  3. Moderate physical activity 150 minutes/ week
  4. 4-5 key components of the AHA Dietary guidelines
  5. Total Cholesterol < 5.0 mmol/l (<200 mg/dL)
  6. BP ~ < 120/80
  7. Fasting Glucose < 6.0 mmol/l (< 100 mg/dL)

Ideal CV Health  Circulation results

Also confirming what I see every day is a high prevalence of “sub clinical” atherosclerosis and cardiovascular disease in “so-called” healthy 50+ individuals.  Note the high background prevalence of sub clinical disease even in normal BMI and normal waist measurement in American men and women (average age 57).

Burden of sub clinical CVD

Prev sub clinical CVD

A very famous paper by Boyd Eaton in The New England Journal of Medicine in 1985 suggested that humans, before agricultural times (>10 000 years ago), basically, did not consume cereal grains. 

Since then a number of toxic components that affect many people beyond celiac disease have been identified.  Cereal grains, particularly gluten-containing grains, have a variety of elements or compounds that are toxic, not just to humans, but to other mammals, birds, and insects. This is precisely why cereal grains have evolved, as these antinutrients protect them from predation. Grains are basically grass seeds and are the reproductive material of a plant responsible for the survival of the species.

Grass family

Plants have taken a number of evolutionary strategies to prevent predation by birds and insects and even pathogens, fungus, and bacteria and perhaps humans. One is that they evolve structures like thorns and hard shells and physical barriers making it very difficult for the predator to get to the seed. To avoid being eaten, cereal grains and legumes have taken on another strategy in which they have evolved toxic compounds (anti-nutrients), essentially to make them unpalatable. PicofWheatThe effect of some of these anti-nutrients is to increase intestinal permeability so that the toxic compound can get past the gastrointestinal barrier and into the bloodstream to interact with our physiology to produce pathological effects.

These toxic compounds in the seeds are more concentrated in the finished product that humans eat in terms of flour-produced products or flour-containing foods and in susceptible individuals cause increased gastrointestinal permeability and multi system pathologies.

There are three compounds in wheat which we know cause intestinal permeability. The best studied of which gluten or, actually, a protein is called gliadin (and related proteins derived from grass seeds). All seem to increase intestinal permeability by a mechanisms elucidated by Alessio Fasano’s group at the University of Maryland. gluten-sensitivityPublished in 2009 these scientists linked a human protein (zonulin) to inflammatory and autoimmune disorders like celiac disease; multiple sclerosis; Thyroiditis; arthritis and diabetes. Alessio Fasano identified zonulin as a molecule in the human body called “haptoglobin 2 precursor”.

Haptoglobin is a molecule that has been known to scientists for many years, identified as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a permutation found only in humans. It’s believed the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people throughout the world.

Dr. Fasano’s study revealed that zonulin is the precursor molecule for haptoglobin 2 – that is, it is an immature molecule that matures into haptoglobin 2. It was previously believed that such precursor molecules served no purpose in the body other than to mature into the molecules they were destined to become. But Dr. Fasano’s study identifies precursor haptoglobin 2 as the first precursor molecule that serves another function entirely – opening a gateway in the gut, or intestines, to let gluten in. 

Apes, monkeys and chimpanzees do not have haptoglobin 2 but 80 percent of humans have it. Apes, monkeys and chimpanzees rarely develop autoimmune disorders whilst humans suffer from more than 70 different kinds of such autoimmune conditions. 

This molecule could be a critical piece of the puzzle in celiac disease, non-celiac gluten sensitivity, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production of zonulin/pre-haptoglobin 2 in response to gluten and other grain proteins, leading to the loss of the protective barrier of cells lining the gut and other areas of the body, like the blood brain barrier.


People who suffer from celiac disease and non-celiac gluten sensitivity (NCGS) have sensitivity to gluten and therefore suffer gastrointestinal symptoms and other systemic symptoms when they eat it.

Seemingly in sensitive people, gluten generates an exaggerated release of zonulin that makes the gut more permeable to large molecules, including gluten itself. The permeable gut allows these macromolecules access to the rest of the body triggering an autoimmune response in which a celiac patient’s immune system identifies gluten as an intruder and responds with an attack targeting the intestine instead of the intruder producing the typical small intestine villous atrophy. An inappropriately high level of production of zonulin also seems responsible for the passage through the intestine of other intruders (other antigens) linking other conditions such as type 2 diabetes, metabolic syndrome, multiple sclerosis and many allergies and autoimmune disease.

Whilst celiac disease is relatively uncommon (~1%) the prevalence of non-celiac gluten sensitivity (NCGS) seems much higher and may be grossly underestimated in the general population.

There are other compounds in wheat that increase intestinal permeability. Extensively studied is wheat germ agglutinin or WGA (a lectin). WGA seems to increase intestinal permeability through two pathways: paracellular and transcellular pathways. In other words the WGA or the lectin can go between cells or it can go through cells through receptor-mediated pathways.


The third component in wheat that increases intestinal permeability is an obscure protein called thaumatin-like proteins. This has been studied in other plant products, but not so much so in wheat. So, we suspect that wheat actually has three compounds: gliadin, WGA, and thaumatin-like proteins that seem to act synergistically to increase intestinal permeability in some people to some degree leading to activation of our immune systems leading to autoimmunity and chronic inflammation with pathological effects on cardiovascular disease, cancers, and other diseases.

WGA is a powerful lectin which seemingly binds to everything including interfering (amongst others) with Vitamin D metabolism. One of the animal models back in the 1980s to study rickets was to feed puppy’s whole grains (wheat).  When the diets comprised 45 to 50% of total energy from grains, they could induce rickets.  Relevant to the development of cardiovascular disease is the association outlined nicely by David S.H. Bell, MD (South Med J. 2011;104 (5):340-344) that Vitamin D deficiency is associated with the risk factors of inflammation, insulin resistance and endothelial dysfunction, and left ventricular hypertrophy. As a result there is an increase in cardiovascular events (CVEs) associated with vitamin D deficiency. Deficiency of vitamin D results in an increased expression of genes that are associated with activation of the renin-angiotensin system and genes that are associated with malfunction of calcium channels.  Therefore, activation of these genes is likely to lead to hypertension, left ventricular hypertrophy and congestive heart failure.

Vitamin D replacement has also been shown to increase high-density lipoprotein levels mainly due to an increase in the size of the high-density lipoprotein particle.  The increase in high-density lipoprotein particle size improves reverse cholesterol transportation (protective to the arterial wall) which has also been shown to improve with vitamin D replacement. 

Epithelial cells contain on their outer surface a glycocalyx.  When you look at a cross-section of flow in an artery, the red blood cells and white blood cells that flow through the artery never touch the endothelial cells because of the surface glycocalyx. The gut is lined with similar epithelial cells preventing macromolecule absorption due in part to the glycocalyx barrier. It prevents large macromolecules (and other antigens) from being absorbed inappropriately. So, we only absorb fatty acids; sugar molecules and amino acids.

WGA like many lectins, bind the glycocalyx causing it to be shed exposing the bare epithelial cells to the gut contents, or in the case of the artery, the contents of the bloodstream. Whenever the glycocalyx is shed in epithelial cells, it causes pro-inflammatory cytokines (TNF alpha, interleukin-2; interleukin-6) that also increases intestinal permeability and compromise vascular integrity (endothelial dysfunction) increasing permeability of the arteries to atherosclerotic lipoproteins causing atherosclerotic cardiovascular disease (ASCVD).

Conventional diets with 60% of daily calories from carbohydrates including a large proportion of grains, may therefore compound (paradoxically) some of the risk for ASCVD with leaky-gut syndrome; dyslipidaemia and high systemic inflammatory burden and autoimmune disease.  h_LDLpathwayThere is a tendency towards lower HDL and to small dense LDL particles size in people consuming high carbohydrate diets including high (often refined) grain intake.  The increased systemic inflammation (high us-CRP) promoting oxidation of the small dense LDL molecules is the typical atherogenic environment to potentiate ASCVD.What-is-Paleolithic-Diet

Perhaps some very good reasons to re-visit a Paleolithic low carbohydrate style diet.



14 thoughts on “Grain Intake – and Cardiovascular Disease

  1. Am confused!! How does this wholegrain theory fit in with low carbs?…interested…
    Sent via my BlackBerry from Vodacom – let your email find you!

  2. Wow, you now officially left the grounds of science and changed into the grainophobic woo-camp? That’s really sad, as this was once a really great blog…
    Come on, really, this piece is literally FULL of unproven claims and assumptions without ANY reasonable amount of evidence whatsoever. All we really DO HAVE is epidemiological data, STRONGLY suggesting that consumption of whole grain products is associated with a lower risk of CVD. So all the mumbo jumbo you present here is hot air pretty much. A hypothesis without any reasonable plausibility! Bookmark deleted.

  3. I am really enjoying the theme/design of your site. Do you ever run into any
    web browser compatibility problems? A handful of my blog audience have complained about my site not working correctly in Explorer but looks
    great in Chrome. Do you have any ideas to help fix this problem?

  4. Found this article very long winded and hard to find the main points and messages in it. Too much info that could have been delivered in shorter lots. Is the whole point to promote paleo?

  5. Not for publication – typo: should be ‘puppies’ as plural of ‘puppy’ – or is ‘puppy’ a manufacturer’s name, like ‘Proctor & Gamble’ or ‘Unilever’? …

    – “WGA is a powerful lectin which seemingly binds to everything including interfering (amongst others) with Vitamin D metabolism. One of the animal models back in the 1980s to study rickets was to feed puppy’s whole grains (wheat). “

    • I mean the theory about homocysteine causing inflammation first…and that’s what the cholesterol sticks to (very basic interpretations here I know(…rather than the level of LDL cholesterol being the cause of atherosclerosis. Is it that you are posing another theory for the inflammation here, or is it linked in anyway to hcysteine levels? thanks

      • Hi Viv

        Thanks for the comment. There are many overlapping components to atherosclerotic vascular disease with the “final common” pathway inflammatory through oxidised lipoproteins. Other players may well be Homocysteine and certainly very high levels of Homocysteine are associated with “athero-thrombotic” conditions especially venous occlusive disease like deep vein thrombosis and pulmonary embolus. In terms of risk however for atherosclerotic arterial disease Homocysteine is only a “weak” risk and so the more conventional players need to be addressed as we have multiple trials worldwide showing that even if you reduce Homocysteine levels with Vitamin B12; B6 and Folate you do NOT reduce the risk of progressive vascular atherosclerosis or reduce cardiac event rates.

        Regards Cardiologydoc

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