In a previous post I talked about the importance of stomach acid and how most stomach acid problems tend to be due to a lack of it rather than an excess (excess acid, it would appear, tends to be a rare thing). One of the causative factors of excess stomach access is the bacteria helicobacter pylori, but rather bizarrely H. pylori is also linked to low stomach acid, too. So, what exactly is going on? Before I get to that let’s take closer look at the bacteria itself. In the first of two posts I’ll be taking a look at the bacteria, how it can cause stomach cancer and more importantly, to my mind, how it affects stomach acid and the dietary implications of this.
A Silent Pandemic?
Current data suggests that 50% of the global population are ‘infected’ with H. pylori. The quotation marks are there because a number of sources now claim that the presence of H. pylori in the stomach may have some benefits. I’ll get round to addressing those in part 2. Prevalence ranges from around 40% in developed countries to around 70% in developing countries (1)
With half of all people on the planet being affected you may think there would be public outcry, but as the vast majority of H. pylori positive people remain asymptomatic, that is, they don’t notice anything is wrong, it doesn’t take a great leap of imagination to see how H. pylori flies below the radar. Acute infection tends to occur in childhood and seems to be rarely recognized (2). It can be easily passed to others through a number of different routes, not just through a fecal-oral route as you might think, but commonly through oral-oral or mouth to mouth transmission (3) though some sources dispute this. It also seems that H. pylori possesses an amazing arsenal of biochemical skills that allow it to survive in a number of hostile environments, which may increase the number of routes of infection (4).
Of course you may say to yourself, with 50% of the world population infected and most people not noticing anything then what’s all the fuss about?
In 1994 H. pylori was classified as a type 1 carcinogen by the International Agency for Research on Cancer, meaning it is a definite cause of cancer. Indeed, it seems that gastric cancer amongst people without H. pylori is very uncommon. According to a 2011 Japanese study of more than 3,100 stomach cancer cases only 21 cases tested negative for H. pylori (5).
Does this mean that if you have H. pylori that you will develop stomach cancer? Not necessarily. According to a 2010 review entitled Helicobacter Pylori and Gastric Cancer: Factors that Modulate Disease Risk long-term carriers have around a 10% chance of developing peptic ulcer, 1-3% chance of gastric adenocarcinoma and less than 0.1% chance of developing mucosa-associated lymphoid tissue lymphoma (commonly referred to as MALT)(6).
The development of gastric cancer involves many different factors which is why only a fraction of people carrying H. pylori go on to develop the condition. Even if you don’t read it through, I suggest you click on the link (6) and scroll down just to get an idea of all the different factors that come into play.
Like all bacteria, the species H. pylori is actually made up of different strains that have slightly different genes and genomes. A 2009 paper mentions a figure of 370 strains split into 7 different population groupings (7). Not only do the genes vary between strains -different versions of the same gene are called alleles- but also the number of genes varies. The same paper gives a figures of anywhere from 1,111 to 1531 genes depending on the strain.
So when we talk about 50% of the global population carrying H. pylori we should also bear in mind that there is a huge variation in the type that they carry and that some types may be more harmful than others.
One of the biggest differences between strains is something called the cytotoxin gene A pathogenicity island (cag PAI). This stretch of DNA encodes a protein, CagA, and what’s known as a type IV secretion apparatus that allows H. pylori to secrete proteins into host cells i.e. the cells that line your stomach. In the US and Europe around 60-70% of H. pylori have the cagA PAI whereas in areas like East Asia nearly all strains possess the cagA PAI (6). Strains with the cagA PAI are associated with a higher risk of ulcers and gastric cancer than strains that lack this particular stretch of DNA.
The CagA protein also varies between strains, too, with some types carrying a greater risk of developing cancer than others. There are other proteins, too, like vacuolating cytotoxin A (vacA) which is present in nearly all strains, but different alleles of the vacA gene result in slightly different proteins with differing levels of toxicity (8,9).
Gastric Acid Secretion, Gastritis and Chronic Gastric Atrophy
Something I find far more insidious than the increased risk of gastric cancer is how H. pylori affects the production of stomach acid. Just like most bacteria, H. pylori, doesn’t like acidic environments and so it has evolved a number of ways of blocking or reducing acidity.
In the first instance an acute infection, i.e. defined as a short term infection, causes hypochlorhydria (low stomach acid). It does this by promoting proinflammatory cytokine IL-1β (cytokines are a type of messenger molecule, this one is part of the immune response) which acts on the acid producing parietal cells. Acid production is also blocked by inhibiting H+K+ ATPase α-subunits on the host cell surface. There are multiple other ways in which the bacteria can block the production of acid, vacA is another guilty party.
The term ‘acute infection’ may be a little misleading in the case of H. pylori, for while an acute infection can bring about abdominal pain, nausea and perhaps even fever, though it can also be completely asymptomatic, it also suggests that once these symptoms disappear then the bacteria has disappeared, too. However, in the majority of cases the infection ‘evolves’ to a chronic state (13). Gastritis is the technical word for the inflammation of the stomach lining that H. pylori causes, so the above would actually be acute gastritis and chronic gastritis. Without antibiotic intervention H. pylori induced chronic gastritis tends to persist for life (11, 12).
There are three different types of gastritis; pangastritis (covering the whole of the stomach), corpus predominant (which affects the corpus or body – the middle) and antrum predominant (which affects the lower part of the stomach).
Pangastritis and corpus predominant gastritis can, over time, lead to hypochlorhydria or even achlorhydria (a complete lack of acid production). These two tend to comprise around 88% of chronic gastritis cases. The remaining 12% is made up of antral predominant gastritis which actually causes hyperchlorhydria (excess stomach acid) and is often what causes stomach ulcers (6). If left for long enough a state known as atrophic gastritis develops in which acid producing cells die and are replaced with other types of tissue. For an informative summary of atrophic gastritis I recommend the Medscape write-up found here (sign up required). Perhaps one of the most worrying aspects is that it’s entirely possible to have this condition and be completely unaware, with minimal if any symptoms almost right up until the point of cancer. Which is one reason why getting hard statistical figures is so difficult, but as the above link notes, with a global infection rate of 50% chronic gastritis is ‘extremely common’. Of course it can quite easily present in some very nasty ways, too, which are also listed on the above link.
Reading through the literature also seems to suggest that hypochlorhydria/achlorhydria are only associated with atrophic gastritis, but H. pylori induced acid reduction can be seen before atrophic gastritis occurs (11)
Disease progression from inflammation to cancer involves many different factors which are excellently summarized in Figure 1 of reference 6 link to expanded version. Progress is in a stepwise fashion; Normal Gastric Mucosa>Superficial Gastritis>Chronic Inflammation>Atrophic Gastritis>Intestinal Metaplasia>Dysplasia>Carcinoma.
Whilst many people talk of eliminating H. pylori to reduce the risk of stomach cancer the fact that chronic infection can lead to low or no stomach acid is, to my mind, much more worrying. Yet, most people who are aware of H. pylori aren’t aware of its tendency to block acid. Here in Japan the high prevalence of H. pylori and its risk of stomach cancer are well known but nearly all people I spoke to are unaware of its acid blocking tendency.
I’ve already written about the importance of stomach acid. Quite simply, if you don’t have stomach acid then you can’t absorb nutrients properly and an inability to absorb nutrients has implications way beyond the small 1-3% chance of developing stomach cancer often later in life.
Studies have shown that people infected with H. pylori have lower levels of several micronutrients; β-carotene, folate, total carotenoids, and retinol (14). H. Pylori is also associated with iron deficiency anemia and lower vitamin C levels (11). Through destruction of parietal cells infection can also lead to pernicious anemia, a disease with a range of symptoms, due to the inability to absorb vitamin B12.
The case of vitamin C is interesting in that it is secreted into the stomach and plays a role in iron absorption but also because it scavenges reactive oxygen species (free radicals) and reduces the formation of N-nitroso compounds, which are thought to play a part in the formation of stomach cancer. Above a pH of 4 vitamin C is irreversibly denatured and can no longer perform this function. Hypochlorhydria is defined as having a gastric pH above 4(15).
A comprehensive review entitled Helicobacter pylori infection and extragastric disorders in children: A critical update discusses several mechanisms, including hypochlorhydria by which H. pylori can retard or stunt growth in children(11). Though it has to be stated that much more research is needed in this particular area.
In part 2 I’ll take a look at some of the claims that H. pylori is a necessary part of our gut microflora, its possible benefits with regards to asthma, allergies and its role in GERD.