Lactose Intolerance

Poor Leonard. He is always being teased due to his lactose intolerance. When he eats yogurts and ice-creams, he "produce copious amounts of methane" AKA farting, diarrhea, irregular bowel movements and cramping. These are symptoms of those suffering from lactose intolerance when they eat dairy products.

He is not the only one though. Real life chef Eva Kende shares her experience as a lactose intolerant individual living with 2 other family members with severe lactose intolerance. She has ran 35 years of a lactose free household and introduces solutions and alternative food to those with the same fate in her website: Eva's Kitchen.
Another lactose intolerant individual, Jamie Forrest, a columnist and cheese expert for "Serious Cheese" articles at seriouseats.com, recently discovered he had severe reactions to dairy products after eating gelato. Ironic isn't it? Read more of his misadventures here: Serious Cheese: What Happens When a Curd Nerd Becomes Lactose Intolerant?

So what is Lactose Intolerance? 
As you all know, lactose is a sugar found in milk and dairy products. Lactose intolerance is when the body is unable to digest and absorb lactose in the duodenum of the small intestine. This is because there is low levels or absence of lactase in the small intestine lining, the enzyme that hydrolyze lactose into galactose and glucose.

Since lactose is not broken into glucose and galactose, the small intestine is unable to absorb glucose and galactose in, and so the lactose is carried on to the colon. Bacteria dwelling in the colon then ferments the lactose, producing gas (thus the farts) which also cause pressure on the intestinal walls resulting in cramps and diarrhea. Usually this happens within 24 hours of consumption.

Let's take a closer look to the main character in this biochemical intolerance: 

LACTASE! (lactase-phlorizin hydrolase)

Lactase is a special type of [beta]-galactosidase on the apical surface of the enterocytes in the brush border villi, facing outwards with a pH optimum of about 6. It breaks lactose into D-glucose + [alpha]-galactosyl intermediate which is further hyfrolysed in D-galactose. It is found only in the small intestine in mammals.

It is a unique enzyme with 2 active sites within one polypeptide chain. One active site is responsible for hydrolysing lactose while the other is for hydrolysing phlorizin. It is also has other enzymatic activities which includes hydrolysing a range of beta-glycosides such as glycosyl, cellulose and aryl [beta]-ceramides.

Thus what happened in Leonard's body is that there is very low level or absence (for some people) of lactase enzyme. 

Plenty of researches have been done to pin-point the causes of this intolerance. With better understanding, correct diagnosis can be done and treatment can reduce or eliminate symptoms effectively. 

1) Causes

There are three types of causes. First is genetics, followed by diseases and recently, researchers find that improper protein structure is also responsible. 

Genetics

In our body, the gene that codes for lactase, called LCT, can exist as 2 forms. If one has the lactase-persistent type, he is able to digest lactose. However if this type is absent, then he cannot digest lactose effectively. As you get older, after age of 5, the LCT gene becomes imbalance and this leads to lower production of lactase. Thus leading to lactose intolerance. [3]

Diseases
Diseases that affects lactose intolerance are such as celiac disease, infectious enteritis, or Crohn’s disease, intestinal bacterial, viral or protozoan infections. These include rotavirus, the protozoan Giardia and gut trypanosomes. Endocrine control through sex and thyroid hormones and ageing, also may affect levels of lactase in the small intestine. When our body is under attack, our cells become stressed and this reduce the production of lactase, especially in gut infections.

Protein Structure
The lactase protein is sensitive to temperature and pH. If it is produced at 37 °C, it will become misfolded, enzymatically inactive and can be destroyed by trypsin. Absence of/inaccurate truncation and cleaving of pre-lactase to mature protein also affects the enzyme's function. Thus, it has to be produced at 20 °C to be functional. [2]

2) Diagnosis and Treatment

Have you ever been in this situation?

30 minutes after you had a bowl of cereal or ice cream your stomach is cramping, it felt bloated and you kept on going in and out of the toilet. Does this sound familiar? Or drink a glass of milk, and the next thing you know you are running towards the washroom. If this does sound like you, you could have lactose intolerance!

However, there isn't really anything to worry about. Studies have shown that up to 90% of South Asian may be lactose intolerant (http://www.pamf.org/southasian/risk/concerns/lactose.html). Lactose intolerance is not a deadly condition, it may however be very frustrating when you have to run to the toilet whenever you eat your favorite sundae. Another thing is that You can't cure lactose intolerance but you can make changes in what and how you eat to reduce its symptoms, such as:

•   Bloating

•   Cramps

•   Diarrhea

•   Painful gas

•   Nausea

Getting a diagnosis

Visit your doctor if you think that you may be lactose intolerant. Your doctor may ask you to keep a diary of what you eat and drink, any symptoms experienced, and prevent taking certain food to see if the symptoms disappear. Sometimes doctors may also suggests to avoid taking any lactose or dairy products for two weeks and see if it helps to relieve the symptoms. This will provide further evidence that you are lactose intolerant.

Further testing may be done to confirm the diagnosis:

Hydrogen breath test

The hydrogen breath test is a very simple and easy one as the air we breathe out have very little hydrogen. Thus if the body does not digest lactose properly, there will then be a build up of hydrogen in the intestine and eventually hydrogen is in the breath*. The test measures the amount of hydrogen(in ppm) in your breath after you drink lactase solution. After a few hours, if your breath contains a large amount of hydrogen (more than 20ppm above the amount of hydrogen in your breath before drinking the lactase solution), it is likely that you are lactose intolerant!

*Additional Info:

Bacteria release a wide range of substances. In low oxygen, bacterial metabolism of lactose and other carbohydrates produces gases and a range of small organic molecules. It is absorption of these that cause the symptoms of lactose intolerance. In order to make ATP, anaerobic bacteria use substrate level phosphorylation instead of oxidative phosphorylation. If the NADH from this is not re-oxidised to NAD, then glycolysis will shut down. In exercising muscle, we do this by generating L-lactate:

 [H+] + NADH + pyruvate ----> [NAD+] + L - lactate

Anaerobic bacteria have evolved several other ingenious pathways in order to remove the H from NADH, through 'fermentation'. Several gut bacteria generate D-lactate instead of L-lactate. Measurement of blood D-lactate can thus be a good indicator of bacterial activity, e.g. in stressed neonates. A major route for removing the H from NADH is through the generation of gases, the cause of flatus. The main gas is [H2] with some CH4 from the archaebacteria. Many bacteria contain an inducible formate hydrogenase, discovered by Marjory Stephenson in the 1930's, converting formate into CO2 and [H2]:

HCO2H -----> CO2 + H2

 The H2 can then act as substrate for the methanogenic archaebacteria:

4[H2] + CO2 ----> CH4 + 2H2O

 This explains why in some patients CH4 is a useful clinical indicator, when lactose ingestion results in little or no H2 in the breath. In this case, H2 has been converted to methane. H2 and CH4 are therefore the main gases in flatus, with some H2S from sulphurous bacteria. Absorption of these gases into the blood allows them to be detected in the breath.

Lactose Tolerance test

This is a blood test that measures the increase in the amount of glucose in your blood after drinking lactose solution. If you can recall, lactose is broken down by lactase to glucose and galactose. Thus, if you are lactose intolerant, in other words have low level of lactase enzyme, your blood glucose level will either rise very slowly or not at all because your body has not digested the lactose.

Stool Acidity Test

This test is for infants and children for lactose intolerance. The reason is because lactose tolerance test and hydrogen breath test requires large doses of lactose, which are dangerous for young children with lactose intolerance. This test measures the amount of acid in stool sample. If the child is lactose intolerant, high amount of fatty acid, such as acetate, is present. This is the result of the product of fermentation of undigested lactose by the bacteria in the colon.

Intestinal/Small Bowel Biopsy

This is the most direct test for lactose intolerance, by directly measuring lactase level in the intestinal lining using endoscope. Low level of lactase indicates lactose intolerance. It is very rare because this is an invasive surgical procedure.

Treatment

Common approach for patients with lactose intolerance are usually by excluding milk and dairy products from their diets. However, this method may affect the intake of calcium and vitamins by the body. Therefore, it is important to realize that not all patients with lactase deficit, only symptomatic ones, have to be treated. There are 2 ways to manage lactose intolerance: Non-pharmacological and pharmacological approach.

Non-pharmacological approach

Initially, milk and dairy products are temporarily avoided for 2-4 weeks to obtain remission of symptoms. Subsequently, a gradual re-introduction of low-lactose dairy products can be suggested, considering the individual threshold dose. (Most individual can tolerate up to 12g of lactose without significant symptoms.)Fermented milk and matured milk products in the diet, milk with pre-hydrolyzed lactose via treatment with lactase supplements, consumption of milk together with other food and distribute lactose intake over the day are several methods to overcome possible symptoms. Paolo Usai-Satta et al have mentioned an interesting approach to increase the threshold dose by increasing the lactose load gradually, giving the colon time to adapt. Since lactase from intestinal brush border is not an inducible enzyme, the reduction in symptoms may be explained by colonic adaptation.

Pharmacological approach

If the measure suggested here are not enough to alleviate symptoms, pharmacological methods can be taken. Enzyme replacement therapy with lactase from nonhuman sources to hydrolyze lactose is another important approach of prevention. There are multiple commercially available lactase supplements containing variable amounts of beta-galactosidase from a variety of sources[5,6,7]. Ingestion of probiotics, nonpathogenic and have lactase intracellularly, may aid in lactose digestion by the intolerant patients. These microorganisms such as lactobacillus and saccharomyces are added to food product or used as supplements [1,3]. Yoghurt containing live cultures providing endogenous beta galactosidase is an alternative source of calories and calcium, and is well tolerated by many lactose-intolerant patients. However, one must take precautions as traces of milk or its derivatives added after fermentations can cause symptoms. Daily supplements of calcium and vitamin D are also recommended to fulfill the dietary calcium recommendation of 1200-1500mg for adolescents. In adults, the amount varies according to gender and menopausal status. [3]Thus we can achieve the goal of treatment , which is to alleviate symptoms while maintaining adequate intake of calcium and vitamin thus preventing secondary bone diseases related to milk-restricted diets.

We hope that all 'Leonard's out there can benefit from these findings in our article to reduce their discomfort and prevent the social embarrassment in this video. 

CAUTION! - EXTREME CASE OF LACTOSE INTOLERANCE. DO NOT TRY THIS AT HOME IN PUBLIC.

REFERENCES:

1) P Usai-Satta, M Scarpa, F Oppia, F Cabras, June 6, 2012, Lactose malabsorption and intolerance: What  should be the best clinical management? [pdf] Available at:<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437438/>[Accessed 4 January 2013]

2) R Jacob, K Peters,H Y. Naim, December 18, 2001, The Prosequence of Human Lactase-Phlorizin Hydrolase Modulates the Folding of the Mature Enzyme* [pdf] Available at: <http://www.jbc.org/content/277/10/8217.full.pdf+html>[Accessed 4 January 2013]

3) R Mattar, D Ferraz de Campos, Mazo, F J Carrilho, July 4, 2012, Lactose intolerance: diagnosis, genetic, and clinical factors. [pdf] Available at: <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401057/>[Accessed 4 January 2013]

4) Campbell, A K. Waud, J P. Matthews, Stephanie B. 2005. The molecular basis of lactose intolerance. Available at: <http://www.freepatentsonline.com/article/Science-Progress/148319659.html> [Accessed on 4 January 2013]

5) Wilt TJ, Shaukat A, Shamliyan T, Taylor BC, MacDonald R, Tacklind J, Rutks I, Schwarzenberg SJ, Kane RL, Levitt M. 2010. Lactose intolerance and health. Rockville: Agency for Healthcare Research and Quality.

6) Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R, Gasbarrini A, Gasbarrini G. Management and treatment of lactose malabsorption. World J Gastroenterol. 2006;12:187–191. [PubMed]

7) Montalto M, Nucera G, Santoro L, Curigliano V, Vastola M, Covino M, Cuoco L, Manna R, Gasbarrini A, Gasbarrini G. Effect of exogenous beta-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study. Eur J Clin Nutr. 2005;59:489–493. [PubMed]

8)NHS,UK. 2011. Lactose Intolerance- Diagnosis. Available at: <http://www.nhs.uk/Conditions/lactose-intolerance/Pages/Diagnosis.aspx>
[Accessed on 12 January 2013]

9)WebMD, LLC. 2011. Digestives Disorders Health Centres. Available at: <http://www.webmd.com/digestive-disorders/diagnosing>
[Accessed on 12 January 2013]