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Heart disease? Then take an indigestion pill

Reading time: 7 minutes

Histamine may have more to do with cardiovascular disease than cholesterol or saturated fats—and an over-the-counter antihistamine could do you more good than a statin, says Bryan Hubbard

As it’s said about history, the theory of cardiovascular disease (CVD)—what causes it and how to treat it—is a story that’s told by the winners. To demonstrate the point, let’s imagine you have worrying signs of heart disease: your doctor offers you a cholesterol-lowering statin or Pepcid, an over-the-counter remedy for indigestion and heartburn. Which one do you choose?

If you reach for the statin, you’ve bought into the story told by the winners. The diet/heart theory maintains that eating saturated fats from dairy and red meat increases levels of LDL (low-density lipoprotein) cholesterol, characterized as the bad cholesterol that clogs arteries and causes atherosclerosis and CVD. The story goes that heart disease can be prevented, or at least controlled, by eating a low-fat diet and taking statins.

If in the extremely unlikely event you instead take the Pepcid—and who in their right mind would choose an indigestion remedy for heart disease?—you’ve just taken the losing side. It’s a broad church that embraces many theories differing in their understanding of CVD, but they all agree that saturated fats and cholesterol have little to do with the disease.

Its pioneers include British nutritionist John Yudkin, whose research projects were defunded because of his claims that sugar—and not saturated fat—was a primary cause of CVD. He clashed with Ancel Keys, the American physiologist who pushed the saturated fats theory harder than anyone else.

Then there’s Theodore “Ted” Hollis, a biologist at Pennsylvania State University who in the 1980s researched the idea that histamine was a driver of heart disease—and that’s where Pepcid comes into the story.

Not just a rash

When we think about histamine, we imagine allergic reactions such as hay fever or perhaps a rash or itchiness if we eat the wrong food. But histamine produces much more than an annoying allergic response; that’s just one of four types of histamine.

Histamines are messenger chemicals that the immune system releases to regulate bodily functions and fight infections and inflammation. Two types (H1 and H2) play a big part in heart functions.

Hollis’s discovery wasn’t new. For over a century, scientists have known that histamine can cause arrythmia, or irregular heartbeat, and that heart patients have more mast cells, white blood cells responsible for the inflammatory response and histamine storage, in their hearts.

So, the pieces that pointed at histamine and inflammation as a driver of CVD were all there long before LDL cholesterol was even a twinkle in the eye of the cardiologist, but nobody had put them together.

Hollis’s research was bought by a drug company that promptly buried it, but other researchers have picked up the trail, including a research team at the National Cardiovascular Center in Suita, Japan. They discovered that Pepcid (famotidine) reduces the severity of heart failure.1

The discovery seems almost paradoxical. People hesitate to take an antihistamine because the drug is often linked to heart problems, but it’s the decongestant element of the remedy that causes cardiovascular complications.

Pepcid is a “histamine H2 receptor antagonist,” which means it blocks the buildup of histamine, especially H2, in the stomach—and also in the heart. Building on Hollis’s discoveries, the Japanese researchers knew that damaged heart cells release histamines, and specifically to H2 receptors, which regulate the heart.

The histamine that binds

The way histamine reacts depends on the receptors it binds to. For Hollis, H1 and H2 receptors were the interesting ones as they are responsible for expanding blood vessels and regulating hypotension (low blood pressure), heart rate and vascular permeability (the ease with which molecules flow through the artery walls). Although all four types of histamine receptors are in the heart, only H1 and H2 are found in heart muscle cells, which are responsible for heart contractions.

As we know when we have a severe allergic reaction—which is the histamines in overdrive—we can have too much of a good thing. Hollis surmised that it was histamine overproduction, and not LDL cholesterol, that caused plaques in the arteries, leading to atherosclerosis.

The Japanese researchers had similar suspicions. They theorized that heart patients who were taking Pepcid for indigestion would also have less severe CVD symptoms, and a trawl of the data suggested they were onto something. Heart patients who were taking Pepcid fared better than others who were taking a different type of stomach medication.

From there, they enlisted 50 heart patients who suffered from indigestion: 25 were given Pepcid, and the others were handed a different remedy that didn’t block histamine activity. The results replicated the outcomes they had seen in their data trawl: the Pepcid group had milder CVD symptoms and were less likely to suffer heart failure. An independent examination by cardiologists showed there was less damage to the heart in the Pepcid group.

Other researchers have also witnessed the heart-protecting qualities of Pepcid. In one 10-year study, healthy patients were less likely to develop heart problems if they were taking an H2 blocker, such as Pepcid,2 while patients with life-threatening pulmonary hypertension—when blood pressure is dangerously high in the lungs—were less likely to die if they were taking the medication.3

It’s the inflammation, stupid

Heart disease has nothing to do with cholesterol and fats but everything to do with inflammation, and that was where Hollis started his research more than 40 years ago. The “winning” diet/heart theory is, in fact, the meshing of two theories: that LDL cholesterol causes atherosclerosis, or thickening of the arteries, and that LDL buildup is caused by eating a diet rich in saturated fats.

The idea that LDL cholesterol plays a part in heart disease has been mooted by scientists for more than a hundred years, but it was only in the 1980s that Ancel Keys won over the scientific community with his theory that our diets play a major role in the disease’s development. The winning combination gave birth to the low-fat foods industry and statins.

But recent studies have questioned one, and sometimes both, parts of the theory. One study of 1,062 patients who had survived a heart attack discovered that they all had healthy levels of LDL cholesterol. “The average cholesterol levels in this group of individuals were quite average,” said researcher Dr Michael Miedema from the Minneapolis Heart Institute.4

A large-scale review of the evidence came to the same conclusion: LDL cholesterol is not linked to CVD and, in fact, is inversely related to all-cause mortality. In other words, the less LDL cholesterol in your system, the more likely you are to suffer a life-threatening chronic disease.5

Undeserving of being demonized as the “bad cholesterol” whose levels must be reduced, LDL cholesterol is essential for healthy cognitive functioning as we get older. People whose cholesterol levels have risen since middle age are 32 percent less likely to suffer from dementia, Alzheimer’s disease and memory loss.

Researchers from Icahn School of Medicine studied 1,897 people aged 75–94 years and discovered the protective qualities of cholesterol became especially significant around age 85. Participants with the highest cholesterol levels weren’t taking statins.6

Angiographs of postmenopausal women with heart disease showed that the progress of atherosclerosis was slower in those whose diets were rich in saturated fats. However, those eating more carbohydrates—or sugars—and polyunsaturated fats were seeing their atherosclerosis develop faster.7

But if you still contend that LDL cholesterol influences heart disease, a diet of saturated fats from meat and dairy products isn’t raising LDL levels. Even people who have a genetic disposition don’t see their levels rise from eating saturated fats, researchers from the University of East Finland have concluded.

They studied 1,032 middle-aged men in Finland, a third of whom had inherited the ApoE4 gene, which affects the way they process cholesterol. But despite eating a high-cholesterol diet—some were consuming around 520 mg of the fats every day—the men’s LDL levels didn’t rise.8

Other studies have confirmed that saturated fats don’t raise levels of LDL cholesterol and don’t contribute to coronary heart disease (CHD), ischemic stroke (caused by a blood clot in the brain) or even type 2 diabetes, often seen as a forerunner to heart disease.9

Instead, it is as Hollis, Yudkin and many others on the losing side have surmised: CVD is a disease of inflammation. A study of more than a thousand heart attack survivors found that those who reduced their levels of inflammation were up to 17 percent less likely to suffer a second attack. Usually, heart attack patients face a 20 percent risk of a second attack within five years.10

Another key is sugar: as Yudkin said all those years back, it’s sugar, and not saturated fats, that drives CVD. Ironically, many low-fat foods are processed and are high in artificial sugars, so people eating them because they think it’s helping their heart are, in fact, doing the very reverse.

If sugar is the catalyst, then insulin resistance also plays a part in CVD, as do environmental stress factors such as childhood trauma. Chronic stress prevents the body from downregulating inflammation, argues cardiologist Aseem Malhotra and his colleagues.11

The Mediterranean diet is a healthy way to reduce inflammation and insulin resistance. Ironically, it was the same diet that Keys was advocating to reduce LDL cholesterol—so he was right for all the wrong reasons.

Despite the years we’ve been taking statins and eating a low-fat diet, CVD obstinately remains the West’s number one killer, but perhaps that’s because we have been following the winning theory of heart disease. It’s time to turn to the losers and recognize that sugars and inflammation are the real culprits and that LDL cholesterol and histamine are the body’s emergency responders.

5 ways to lower insulin levels

  • Eat a Mediterranean diet that comprises 40% fat
  • Drink 4 tablespoons of extra virgin olive oil a day
  • Eat a handful of nuts a day
  • Take a brisk walk for around 20 minutes a day
  • Do some moderate activity for 30 minutes a day

5 ways to lower histamine levels

  • Use essential oils, such as chamomile and lavender, in a diffuser or add a few drops to your bath
  • Aim for at least seven hours of sleep every night
  • Meditate or practice yoga to lower your stress levels
  • Stay hydrated by drinking around eight glasses of water a day
  • Do moderate exercise every day for 30 minutes

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References
  1. J Am Coll Cardiol, 2006; 48(7): 1378–84
  2. Ann Am Thorac Soc, 2014; 11(9): 1379–86
  3. Am J Respir Crit Care Med, 2018; 197(12): 1638–41
  4. J Am Heart Assoc, 2017; doi: 10.1161/JAHA.116.005333
  5. BMJ Open, 2016; 6(6): e010401
  6. Alzheimers Dement, 2018; 14(7): 952–60
  7. Am J Clin Nutr, 2004; 80(5): 1175–84
  8. Am J Clin Nutr, 2016; 103(3): 895–901
  9. BMJ, 2015; 351: h3978
  10. New Engl J Med, 2017; 377(12): 1119–31
  11. Br J Sports Med, 2017; 51(15): 1111–12
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