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What is the Real Cause of Gout? Biochemistry Links Obesity, Cardiovascular Disease and Gout

Posted by nikh

Gout is a disease caused by increased uric acid in the blood. This article highlights possibly the real cause of gout, and this is explained with biochemistry.

Wikipedia describes gout as “a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected (approximately 50% of cases). However, it may also present as

  •  tophi (urate crystals deposited in cartilage and bones causing destruction to the tissues),
  • kidney stones, or
  • urate nephropathy (kidney function damage caused by high uric acid levels).

All of which are related to gout and is caused by elevated levels of uric acid in the blood. The uric acid crystallizes, and the crystals deposit in joints, tendons, and surrounding tissues.”

We know that Gout is caused by increased uric acid content in the blood — somehow the body produces too much uric acid and these crystals end up in parts of the body (like joints), causing painful inflammation.

What is Uric Acid?

Uric acid is a by-product of purine metabolism. In excess, uric acid becomes a waste product that causes tissue inflammation.

Purines are a group of compounds called nucleotides. These compounds are essential for life. They make up the genetic material (DNA and RNA),  as an energy carrier as Adenosine triphosphate (ATP), its pre-cursor ADP, and as co-enzyme NAD / NADP .

 

The Function of Purines

Purines are essential for the function of all living cells in the body:

  • As part of DNA and RNA genetic coding. This is the basis of  all living cells and even viruses.
  • Are important biochemical molecules such as ATPGTPcyclic AMPNADH, and coenzyme A.
  • are contained in neurotransmitters for brain and nerve function.

Healthy human body uses and converts one form of purine to another depending on requirement of the cells. Excess purines are converted to uric acid for active removal from the body via kidneys. This regulatory process is balanced.

purine metabolism

Sorry about the above diagram. You do not need to study this, just note where urate (uric acid) is derived from.

uric acid formation from Adenosine

Adenosine and it’s derivatives are most common of the purine types in metabolic and biochemical pathways.

You can read more about adenosine in wikipedia : http://en.wikipedia.org/wiki/Adenosine, but it isn’t necessary. Basically:

  • Adenosine, when phosphorylated becomes ATP which is used for energy when ATP –> ADP. ( Read also: What does it Really Mean to Burn Calories?)
  • ATP dephosphorylates to release energy to become ADP and the AMP.
  • AMP dephosphorylates to Adenosine, and Adenine.
  • Adenine is converted to uric acid and removed from the body.

Gout is  an unhealthy situation. It happens because of an overload of uric acid.  Could it be derived from an overload in Adenine production?

If so how? from where?  Read on, please… and don’t mind the biochemistry. It’s the only way to explain this.

Gout is Linked to Obesity

Obese people are 4 times more likely to suffer gout. There is also links between gout and metabolic diseases like type II diabetes, cardiovascular disease, hypertension.

obesity gout risk

http://www.ncbi.nlm.nih.gov/pubmed/15824292

You can find many scientific articles that link gout to obesity — and not only obesity but other metabolic diseases.

Obesity is a marker for metabolic diseases. This means that obesity is a sign that a person is most likely to suffer or will suffer metabolic disease. It does not mean that every obese person will suffer metabolic diseases. It also does not mean that non-obese persons are free from metabolic disease risk.

In fact, naturally thin people (ectomorphs) are at greater risk of developing metabolic diseases than others at lower BMI.

Read also: Why Thin People Should Be More Careful About Diet and Exercise

We all risk metabolic syndrome when we consume too much refined carbohydrates (especially fructose) and alcohol — and if we do not have enough physical activity to utilize the excess energy from those nutrients.

The Obesity – Gout Link — biochemistry

Scientist have linked the onset of gout with obesity and metabolic disorder. They have also linked abnormally high levels of homocysteine in the blood ( hyperhomocysteinemia) with patients of metabolic disorder (in particular heart disease) and gout.

Elevated serum homocysteine levels for gouty patients

http://link.springer.com/article/10.1007/s10067-004-0978-4

 

Homocysteine is not derived from diet. It is biochemically generated in our body.

Why, if this compound has harmful effects, does our body suddenly produce too much of it?

We should take a look at how homocysteine is generated — > sorry, biochemistry again!

Homocysteine – Methionine Cycle

Homocysteine is a by-product of methionine. Methionine is an amino acid, that is derived from protein. Methionine converts to homocysteine and back to methionine in a reaction called the Homocysteine-Methionine cycle.

This is how it looks.

homocysteine - methionine

http://en.wikipedia.org/wiki/Methionine

In healthy body, the cycle goes in a way that homocysteine will never be in excess — this is because it converts back to methionine.

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Interesting points to note with this pathway:

1. Accumulation of homocysteine

If homocysteine is abnormally high in blood (as in unhealthy individuals),  this only means that the reaction is driven excessively in 1 direction faster (1 — > 2 –> 3) and slower in reaction 4. (see figure above).

2. Accumulation of Adenine

If the homocysteine production is elevated, more adenine is also produced.

Remember that Adenine (in excess) –> Uric acid

3. What is X?

There is a purpose for methionine –>homocysteine  path : to attach a methyl  (-ch3) group to some compounds that need methylation.

X –> X-CH3

Could it be that there is an abnormally big demand for methylating X that caused the reaction to go faster in one direction? Could it be that there is unusually big demand to produce X-CH3 molecule?

What could X-CH3 be?

Phosphatidylcholine (or lecithin).

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Note : Some scientists are sure that homocysteine levels are linked to substrates like X that need methylation as with this article http://www.nature.com/hr/journal/v34/n12/full/hr2011133a.html.  However, like doctors, they jump to the conclusion that the compound, X, comes directly from food or the environment.

When we try to sort out causes of metabolic disorder, it is better to look at lifestyle, and see what causes the body to generate/accumulate these markers rather than to assume direct origin from food.

The Liver Generates Phosphatidylcholine to Cope with Fat

Phosphatidylcholine (also known as lecithin) is a very important component of cell membranes. We get it in our diet when we consume good fats like egg yolk. The liver also produces phsophatidylcholine. http://en.wikipedia.org/wiki/Phosphatidylcholine

In individuals who consume excessively refined carbohydrates, fructose sugar and alcohol, much of the excess enters the liver. The liver cells metabolises these to fat.

Problem with fat is, that it cannot stay in the liver. Fat has to be removed from the liver and transported to fat cells — failing this leads to a condition of fatty liver. http://en.wikipedia.org/wiki/Fatty_liver

In order to remove fat from liver, fatty acids are packaged into lipoprotein complex called VLDL (very low density lipoprotein).  VLDL moves out of the liver via the blood stream and transports the fat in it to fat cells.

Guess what is needed to make VLDL?

Phosphatidylcholine!

Phosphatidylcholine Production Leads to Accumulation of Homocysteine and Adenosine

Read all about phosphatidylcholine here: http://lipidlibrary.aocs.org/lipids/pc/index.htm

 

Phosphatidylcholine - vldl

http://lipidlibrary.aocs.org/lipids/pc/index.htm

This reaction happens in the liver, especially if phosphatidylcholine is deficient: Phosphatidylethanolamine gets converted to phosphatidylcholine through 3-step methylation process. This process is helped along by methionine – homocysteine cycle.

As I’m writing this, I notice that there requires 3 rounds of methylation to produce 1 molecule of phosphatidylcholine. This means 3 x homocysteine and 3 x adenine produced in the process.

 

From this, perhaps we can say that in the liver:

Fat production requires –> VLDL to transport fat out of liver –> increased production of VLDL –> needing more Phosphatidylcholine –> build up of homocysteine and adenine (uric acid)

Looks like it

So, What Really Contributes to Gout?

Diet.

refined carbs

excerpt from Forever Young Forever Fit

The liver converts excess energy from nutrients to fat. VLDL is produced to remove fat from the liver. VLDL is built on phosphatidlycholine and it’s production could be a cause of increased uric acid in the body.

Excess food intake is the cause of liver producing fat. However not all food nutrients contribute to liver fat synthesis equally.

Fructose  is a component of table sugar, fruits and naturally sweet foods like honey. All fructose consumed in the diet has to be processed in the liver, since other cells in the body cannot use fructose. Consumption of sweet foods in excess is a cause of gout.  The problem with fructose laden foods is that we consume them with abandon: in soft drinks, desserts, sauces, candy, confeectionery, etc.

Alcohol has the same effect as fructose. Most of the alcohol we consume has to be processed in the liver. Overconsumption of alcohol is known to be reason for gout.

Refined carbohydrates consumed releases free glucose into the blood. These foods are easy to eat and we eat lots of it. Most of us consume more calories of refined carbs than we can burn with activity. Excess glucose ends up in the liver and some are converted to fat.

The key to eliminating uric acid in the blood is to take refined carbs, alcohol and fructose out of the diet.

Why Protein, Fat and Purines in Diet are Unlikely Cause of Gout

Fat in diet  –> fatty acids transported to the blood as chylomicrons. Most of it enters the blood stream and into other tissues of the body without entering the liver.

Protein in diet –> breaks down into amino acids. Most of it is used for building body proteins, and the rest is excreted in the urine as urea. That which turns to fat is small percentage.

Most of us consume far more refined carbohydrates, sugar and alcohol than fat and protein.

Why do Doctors think protein or purines are to blame?

If we simply look at the biochemical pathway in pieces, it might seem that because uric acid is the cause of gout, and uric acid is by-product of purine, purine in food is the cause. Fact is that the body can regulate purines pretty well in a healthy body. In the case of gout sufferers, the liver has to ‘save itself’ by producing VLDL to cope with the excess fat it has to synthesize.

Excess sugar and excess alcohol in liver –> fat production –> VLDL production + Adenosine + Homocysteine –> uric acid

Doctors may think proteins are blame because they confuse uric acid with urea. They are both very different compounds from different pathways and different sources.

Treatment of Gout

The best treatment for disease like gout is a change in lifestyle. No medication / supplement in the world will help in the long term as effectively as a change in diet.  Most drugs for gout are painkillers and these work by reducing inflammation. This is a double edged sword, because inflammation helps the body heal itself. Many painkillers, espcially steroids bring bad side effects.

“No disease that can be treated by diet should be treated with any means.”  Maimonides

Consider Diet Change

Change your diet first.  You may find the recommendation below different from some articles circulating the net. The advice given below is based on the theory I have put forth here.

Consider cutting out all refined carbohydrates in your diet. Consume no sugar containing foods, and drink no alcohol.

Consume less carbohydrate loaded foods like starchy vegetables (e.g. potato), cut out all grains (rice, wheat, oats, corn) and limit very sweet fruits like banana.

Eat whole foods that are non-starchy.

Eat protein from meats and meat products including eggs and cheese.

Eat fats like olive oil, butter, coconut oil.

Consume lots of fresh vegetables (especially leafy ones), nuts and seeds, avocado and coconut.

 

It may be worthwhile to consider foods rich in lecithin (egg yolk) because this may alleviate the homocysteine cycle.

If you have liver issues…

If your liver is weak (which is common with people with gout), you may need to lower protein intake but eat more fat and vegetables.

Feed your body with whole foods…

You need to eat whole foods. Fresh meats, eggs, vegetables, nuts, seeds and cheese are rich in essential fatty acids, lecithin, vitamins (esp B vitamins) and minerals that will help your liver recover good function.

Exercise can help because it depletes your glycogen stores and reduces the amount of fat your liver will make from carbs. However, this has limited use if your diet is sugar and alcohol rich… sorry.

Exercise anyway! You need mobility and muscles for health!

If this theory is right…

My inspiration to do this research came from discussion I have had with friends who suffer gout. Many are puzzled by doctors advice on diet, and many of the drugs administered for gout only works to relieve pain (plus some scary side effects).

I have not found (at this time of writing) any blog post that has put these pathways together. I have scoured blogs, looked at pathways more closely, and put this information together. I think it makes sense, but it is up to you to decide.

If this theory is right, then it proves that this is a problem related to many problems. It is a problem caused by a certain type of diet which many people adopt — high carb high sugar diet.

 

 

 

Other interesting reads:

Choline – Linus Pauling Institute

Nucleotide metabolism

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