Understanding lactose intolerance requires a brief history of the agricultural revolution- the period of human adaptation of crop and livestock cultivation. Early archeological evidence suggests that the agricultural revolution originated in Egypt approximately 9,000 years ago and spread to the Middle East no later than 7,700 years ago during the Neolithic period.
The advancements made during this period led to drastic changes in human society. The addition of new cultivated plants and animal products led to diversity in the types and amounts of foods that were consumed. Crop and livestock cultivation also phased out foraging and led to increased settlements and sedentarism. Crop and livestock cultivation meant that foods could be stored, food variety increased, and food could be available at all times. The cultivation of staple crops of wheat, barely, and rye in this geographic area and the beginning of large-scale animal farming for food production shaped how and what we eat today (1-3).
The Food and Agriculture Organization of the United Nations states that, "today, 75% of the world’s food is generated from only 12 plants and 5 animal species. Of the 250,000 to 300,000 known edible plant species, only 150 to 200 are used by humans. Only 3 – rice, maize, and wheat – contribute nearly 60% of calories and proteins obtained by humans from plants” (4). In addition, people now worldwide consume wheat, dairy, and animal meat products as part of their regular diet. Consumption of these products has also shaped the human genome and has contributed to our genetic evolution.
Milk and Lactose
During infancy, breast milk is essential for infant nutrition and fatal if not digestable. The key carbohydrate nutrient derived from milk is called lactose. Lactose is a disaccharide that is made up of the subunits glucose and galactose, it is a key source of nutrition in all mammals except the sea lion (5). Lactose is absorbed in the intestines by the enzyme, lactaste-phylorizin hydrolase (lactase). As babies are weaned from breast-feeding and new foods are introduced into the diet, lactase activity beings to decrease. However humans are the only mammals that continue to consume milk after infancy. This is largely due to the proliferation of livestock farming and persistent consumption of milk and dairy products in the human diet. Because of this, the human genome changed and the trait that gives humans the ability to digest lactose, the lactase persistence trait, developed. The lactase persistence trait is a dominant Mendelian trait that is most prevalent in people from northern Europe populations including most of the Scandinavian countries and Holland (2). Trait prevalence is lower in people of southern Europe and Middle Eastern descent. It is estimated to occur in about 50% of people in Spain, Italy, and pastoral populations of the modern regions of Turkey, Syria, and Iran. Humans with the lowest prevalence of the lactase persistence trait are largely from most Asian and African populations except societies that were large pastoralist populations such as the Tutsi in Rwanda and Burundi and the Fulani who are widely dispersed in Western African countries including Mali and Nigeria (3).
The lactase persistence trait is a great example of human genetic evolution. The physiologic ability of an adult human to be able to digest lactose from the milk of other mammals meant that people were able to benefit from the nutrition of the milk carbohydrate for fuel. Moreover, it provided additional nutritional components of milk including fat, protein, calcium, and other vitamins. In climates where water was scarce, milk also became an important source of water. If a person was intolerant and unable to digest lactose, diarrhea and subsequent water loss from diarrhea might be considered an evolutionary disadvantage. But is lactase persistence an evolutionary advantage or does it just characterize a moment in time that marks the agricultural revolution in humans?
Lactose Intolerance
In our modern time, lactose intolerance is poorly understood. It is commonly used as a generalized term that refers to a constellation of gastrointestinal symptoms that a person can experience after consuming milk and/or other dairy products. However one can experience gastrointestinal (GI) symptoms regardless of whether they have the lactase persistence gene and moreover, there are many genetic variants of the gene.
Why does GI distress occur when some people drink milk or eat dairy?
The most common symptoms of GI distress after consuming milk or dairy are gas, bloating, and diarrhea. When a person is unable to digest lactose, the undigested lactose is subject to fermentation by the microflora of the large intestine. The malodorous gasses that are produced when a person has difficulty digesting lactose are due to fermentation by the microflora.
The symptoms and severity of GI symptoms from consumption of milk and dairy are related to a variety of factors including the regularity of lactose intake, the type of milk or dairy product consumed, the additional components that are consumed with the milk or dairy product, age, and the microbiome. It has also been shown that symptoms of lactose intolerance often do not occur until there is less than approximately 50% lactase activity. It has also been shown that people lacking the lactase persistence gene may tolerate small amounts of lactose (about 12-15 grams which is equivalent to one cup), especially if the milk or dairy product is combined with other foods and if consumption is spread throughout the day (5, 7, 8). Various GI diseases such as small intestinal bowel overgrowth (SIBO) and other inflammatory diseases of the GI tract, metabolic conditions, and nutrient-drug interactions are additional factors that may contribute to GI distress following the consumption of milk or dairy.
From a clinical perspective, the terms related to lactose intolerance and absorption are the following:
- Lactase deficiency is defined as reduced lactase activity in the small intestines that leads to lactose malabsorption
- Lactose malabsorption occurs if there is a substantial amount of lactose that is not absorbed in the small intestine
- Lactose intolerance characterizes the constellation of GI symptoms related to lactose malabsorption such as gas, bloating, abdominal pain, and diarrhea
From a clinical perspective, it is difficult to test for lactose malabsorption and intolerance and one of the most helpful interventions is a dietary elimination protocol for milk and dairy products. Clinical procedures and tests include small intestine biopsies and genetic tests however these tests do not quantify symptoms and genetic tests may be difficult to interpret. Patients can also be highly symptomatic or have no symptoms regardless of positive biopsy or genetic findings (1, 5, 6). Finally, lactose intolerance is an example of the increased prevalence of food allergies and sensitivities in humans. There are many questions that need to be studied with regard to links between environmental changes, genetic variants, and the increasing prevalence and risk of developing food allergies and sensitivities.
Summary
The lactase persistence trait and its variants are a strong example of genetic changes in humans that occurred likely due to broad changes in human civilization. Lactose intolerance is the clinical term that is commonly used to describe the symptoms related the malabsorption of lactose, the main carbohydrate found in milk and dairy products. Symptoms of lactose intolerance commonly include gas, bloating, abdominal pain, and diarrhea and the presence and severity of symptoms can also be confounded by preexisting conditions and other factors. Lactose intolerance is related to lactase deficiency that may or may not be due to the presence or absence of the lactase persistence genetic trait. The example of lactose intolerance brings to light common questions and areas of future study. Some of these include the impact of environment on our genes and the increased prevalence of human food allergies.
References
1. Tishkoff SA et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007 Jan;39(1):31-40.
2. Swallow DM. Genetics of lactase persistence and lactose intolerance. Annu. Rev. Genet. 2003; 37:197–219.
3. Blanchard C. A history into genetic and epigenetic evolution of food tolerance: how humanity rapidly evolved by drinking milk and eating wheat. Curr Opin Allergy Clin Immunol. 2017 Dec;17(6):460-464.
4. Food and Agriculture Organization of the United Nations (FAO). 1999b. Women: users, preservers and managers of agrobiodiversity (available at www.fao.org/FOCUS/E/Women/Biodiv-e.htm).
5. Deng Y et al. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.
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6. Misselwitz, B et al. Lactose malabsorption and intolerance: Pathogenesis, diagnosis and treatment. United Eur. Gastroenterol. J. 2013, 1, 151–159
7. Shaukat, A et al. Systematic review: Effective management strategies for lactose intolerance. Ann. Intern. Med. 2010, 152, 797–803.
8. Lomer, M.C.; Parkes, G.C.; Sanderson, J.D. Review article: Lactose intolerance in clinical practice—Myths and realities. Aliment. Pharmacol. Ther. 2008, 27, 93–103.