Thursday, June 22, 2023

Is Milk Intolerance Genetical? A Question was Asked by a Reader. Can We Solve this Nutritional Problem?

 

 

A question was asked in the comment column under this article:

“Why Most People Cannot Tolerate Drinking Milk” in this link:

https://scientificlogic.blogspot.com/2023/

It reads:

“Very interesting explanation. My eldest brother who is 41 years old, 15 years older than me, can tolerate drinking milk, but not myself. He has been drinking milk regularly since he was young without problem, but not myself. I get severe diarrhea if I do.  We are both from the same parents. So, there should not be any genetic difference. Why then is this difference in tolerance and health problems?  Maybe you have the answer?

Sussie Chan”

……………………………………………………….

My answer to Sussie:

Thank you, Suzzie for your comment and question in my article “Why Most People Cannot Tolerate Drinking Milk”?

Before answering your question, let me explain just a little bit about genetics, and environmental influence on genes. Just a bit will do together with other ‘irrelevant’ information if you don’t mind so that we can understand nutrition better. Nutrition is far, far more than just what food to take, what food to avoid or what foods are health-protective, others disease causing. 

The study of nutrition is a hectic formal 4-year degree course involving almost the entire spectrum of biological, biomedical sciences,   chemistry, biochemistry, chemical analysis of foods statistical analysis, sociology, agriculture and food production, soil science, behavioural science, clinical medicine, especially in the diagnosis and recognition of nutrition and nutrition-related diseases, These were subjects in our formal intensive training during our postgraduate study at least at the University of London. But I have little idea about other universities what they were taught there?  The study of nutrition is done from bachelor’s to master’s levels, onwards to doctoral and well past doctoral levels. So, what I shall explain here is only a teeny-teeny tiny glimpse of it so that we can answer your question better.  

Although there is genetic similarity between you and your brother, bear in mind genes do influence social behaviour besides the types of proteins it expresses. Each cell expresses, or turns on, only a fraction of its genes at any given time. The rest of the genes are repressed or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, as examples. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood.

Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is passed to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine when and how much protein product is made by a gene.

Lactase deficiency is believed to be genetically programmed to produce this protein enzyme lactase that breaks down milk sugar lactose into lactic acid and other products.  Its ability to do this is age-related as the LCT gene responsible for the production of lactase becomes progressively latent with time. According to some studies LCT genes remain active between the ages of 5-20 years.

It was once thought that genes do not change. But recent research in the field of epigenetic showed that genes do change in response to the environment, and they are capable of changing their cellular behaviour including the social behaviour of the individual.  It is the case of nature vs nurture. In fact, it is their ability to change especially to the environment as a stimulus that is the very reason how all living organisms begin to adapt for the better. This is not something new as we think.

As far back as in 1864 Herbert Spencer in his “The Principles of Biology” looked at Darwin’s evolution as “Function, Adaptation and Variation” of the various species of life where he introduced the expression 'survival of the fittest', in the sense of 'the most appropriate to its environment'. Scientists have only recognized this behaviour and adaptive changes only recently, and they gave it the name of this new study called ‘epigenetics’.

Epigenetics is the study of the environment and its impact on behaviour, and how the changing environment affects the way the genes are going to express themselves. Gene expression means the process by which the information encoded in a gene is turned into a function. This mostly occurs via the transcription of RNA molecules that code for proteins or non-coding RNA molecules that serve other functions.

Unlike genetic changes, epigenetic changes are reversible and do not change the DNA sequence, but they can change how the body reads a DNA sequence.

Another way of explaining this is, the environment influences the behaviour of our genes and how they work for us, even though the environment does not change the DNA sequence, but they can change how the body reads a DNA sequence to change the way we behave and react.

For example, a pair of identical twins born from birth but brought up separately in different environments and social influences may have entirely different social characteristics and behaviour though their physical features remain identical.

In the same way we may explain why two identical twins or as in your brother case, and yourself as a sister, your brother is drinking milk persistently till age of 41, and he becomes milk tolerant, whereas with yourself who does not, becomes intolerable to milk and lactose. This may be due to adaptation when your brother is constantly exposed to the same dietary environment that induces the LCT gene that produces lactase to remain active lifelong, whereas for others like yourself where milk was switched off in favour of other foods, has caused the lactase-producing genes to switch off when no longer stimulated or needed.

Hence, it is not surprising to me that your eldest brother, though has genes similar to yours, has adapted for the better by stimulating his genes to adapt to milk drinking since a baby till he is now 41 years, whereas your similar parental genes have not. I suppose your parents may have traditionally been feeding him milk since a baby 15 years earlier than yourself since social behaviour does change over just one generation from past traditions to recent trends, and that could have affected the genes to continue to express the enzyme lactase to break down the lactose in milk.

This is precisely what I mentioned earlier in my article on milk intolerance that milk (milk sugar lactose) affects mainly the Asians, predominately the Chinese whose mothers took off their babies from milk far too early after one year instead of allowing them to continue with milk as a supplementary food after weaning them to other foods. The problem about nutrition is, it is such a complex mixture of scientific-medical-social-economic-behavioral-anthropological field of study that we know so little about their interactions, such as what food is exactly right for us, or when to switch over from milk to other foods. We must bear in mind milk like eggs for a developing chicken that is still incubating inside the eggs for 21 days is the only food for the chick, as with milk as the only complete food for all mammalian babies including human babies.  

In fact, nutritionists recommend that a baby should be given other foods as early as 6 months, although they did not actually suggest that milk should not be given after 6 months. In other words, the nursing period of 6 months does not necessarily mean that milk should not be drunk after that, bearing in mind milk is still the complete food rich in all nutrients that could support the growth of a body till even well past one year, not just for 6 months as nutritionists recommend. I have seen children drinking milk even at 5 years old and they look very healthy and active. Perhaps milk may not have sufficient calories to support the energy requirements of a growing child. Milk is so good and complete in nutrients that calves that are much heavier and stronger than human babies feed on them from mother cows till it becomes almost an adult cow, buffalo or a bull. These animals, as with all other mammals that feed their young till they can thrive on their own food, have no problem with milk or lactose intolerance, only humans. I suppose our busy commercial and economic lifestyles are such that we have no patience in breastfeeding or to continue to bottle-feed our babies as long as they want the milk.

Human milk contains 3%--5% fat, 0.8%--0.9% protein, 6.9%--7.2% carbohydrate calculated as lactose, and 0.2% mineral constituents expressed as ash. Its energy content is 60--75 kcal/100 ml.

The energy requirement of a child from 1 - 5-year-old is generally 100cal/kg/day between 1 to 3 years old, 80 kcal/kg/day, between 4 to 5 years, and 70 kcal/kg/day, 6 to 8 years needs 60 to 65 kcal/kg/day from 6 to 8 years, and for 9+ years he / she needs between 35 to 45 kcal/kg/day. Our problem is that food is like medicine. We know a lot of things in medicine, but surprisingly a lot of information on nutrition remains unknown to us. So, milk alone may not be sufficient in quantity to support accelerated growth in a child, and other foods need to be supplemented after 6 months of weaning.

In medicine, drugs are used, and we know a tremendous lot how they react in the body (pharmacodynamics) and how the body deals with them (pharmacokinetics) because all drugs are just pure organic compounds, mostly synthetic, and we can easily trace their pathways in the body – how they are metabolized and excreted from the body. But with food as a medicine, especially plant-based, they contain tens of thousands if not millions of phytochemicals and medicinal values, not just nutritional values in them. 

Furthermore, if they are eaten in a wide variety, how are nutritionists and nutritional scientists going to know how they are going to react in the body, let alone their phytochemicals reacting and cross-acting with each other on ingestion?  It is almost impossible to know or to trace their metabolic pathways.  That is the reason we often receive all kinds of unsubstantiated health, often contradictory health-protective, or health-damaging claims about foods in videos, WhatsApp, advertisements, health magazines, newspapers and in social media. Everyone is taking advantage of our ignorance.  

Nutritionists now call foods that have other nutritive or medicinal functions as “functional foods” defined as foods that contain, in addition to nutrients, other components that may be beneficial to health or have a potentially positive effect on health or their medicinal therapeutic values beyond basic nutrition.

Traditional standard food composition tables give us the nutritive valves of the major food chemical components – carbohydrates, proteins, fats, vitamins, and minerals. Some food tables provide us values of trace minerals as well. But none of the food composition tables tell us anything about “non-nutritive” substances, yet health-protective principles in them – the tens of thousands of naturally-occurring phytochemicals and their protective or medical properties bestowed by Nature for us as medicines as well. It is almost impossible for any analytical food scientist to analyse them all, let alone for nutritionists to study their health impacts on the body.

The National Institutes of Health (NIH) is the largest funder on health issues, with nutrition research investments estimated at $1.9 billion annually (5% of total NIH funding) for fiscal year 2019. Approximately 25% of this funding (1.3% of total NIH funding) focuses on diet for the prevention or treatment of disease in humans, and yet we know so little about how food can affect the body and health. This is only in America. World-wide nutrition research takes precedence over all other medical research. World-wide it is estimated the annual expenditure spent on nutrition research exceeds US 100 billion dollars resulting in an avalanche of research papers published with a bit of inroads made on how food affects our health and on  latency of diseases yet to come, yet we still know only a little. Nutrition for health is probably the most favourite and popular subject ever written very often in women and man magazines, and widely  discussed in all print and electronic media including on television and on radio, including messages and information circulated in WhatsApp chat groups.  

Only cancer research at US$2.9 billion in 2020 exceeded that of nutrition research. Previously it was nutrition and nutrition research that occupied the central stage in health care. These are the only two areas, cancer and nutrition research that are given the highest priorities in medical research and yet we cannot completely solve problems on disease under these two fields. Let’s take just these two examples: nutrition and medicine.    

In medicine for instance, we know the dosage of the drug to give. We can titrate the dose to the patient’s needs. We can adjust it to a person's body weight up to the maximum dose allowed according to the drug manufacturer’s instructions.

But with food it is so complicated that we only have some idea how much nutrient intake to recommend, but not give to an average person. Nutritionists call this as “Recommended Daily Allowances (RDA).  We can only recommend a certain plus and minus allowance because we do not know exactly how much intake is needed for each nutrient for optimal health. It varies so much for individuals according to their age, sex, physical activities, childbearing or not, genetic make-up (ethnicities), body size and weight and even their health status.

Even for health we cannot give any specific or single definition.  W.H.O. in its Constitution gave a very broad holistic definition of health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” That definition does not even tell us or explain what then “optimal health” is?   

Thus, the recommended daily allowance for food intake is based on numerous studies done on as huge a population who are in apparently good health, and the average taken based on so many influencing factors such as age, sex, morbidity and mortality, food consumption, types of foods and quantities consumed, metabolic activities, active and sedentary lifestyles, disease patterns, and so on. These recommendations are not even fixed. In most countries they are revised every 5 years by a huge committee of highly powered medical and nutrition experts because nobody knows the precise “dosage” for nutrient requirements, unlike we do for drugs.   

The RDA is the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in a particular life-stage and gender group. The RDA is the goal for usual intake by an individual.

The RDA depends not only on age, gender, physical activities, but also on environment temperatures, food availability, social, cultural, personal, psychological, economic factors, let alone state of health, beliefs, food taboos among others. It is a highly, highly complicated problem so unlike in medicine where problems on disease, drugs indicated, and dosages are so clear cut to us.

Coming back to the nutritional problem, what strategy can we implement to solve, if not reverse lactose and milk intolerance.  Perhaps one answer is, we can use lactose-breaking bacteria found in the colon (beneficial human microbiota – the colonic microbiome) that has endogenous lactase activity,

These bacteria can break down lactose (milk sugar) into lactic acid. Some of these lactose-bacteria called Lactobacillus and Bifidobacterium, especially Lactobacillus bulgaricus and Streptococcus thermophilus are also found in yoghurt. They possess beta-galactosidase activity (bacterial lactase) that allows them to digest and utilize lactose. These bacteria hydrolyse the lactose to glucose and galactose and subsequently ferment them to lactate, short-chain fatty acids (SCFAs), and gases, such as H2, CO2, and CH4 Although Bifidobacterium bifidum expresses lactase activity, no clinical trials have determined its impact on lactose-intolerant subjects.  

Unfortunately, in normolactasia (normal lactate), when intestinal lactase is high, only a small percentage of ingested lactose reaches the colon.

Lactose cannot be directly absorbed in the intestinal tract and must, instead, be broken down into its two smaller component sugars by an enzyme called lactase and hence they cause intestinal disturbances if they stay there unbroken down and unabsorbed.  Normally, the activity of the LCT gene that produces lactase, LCT, declines after infancy. Recent evidence suggests that a decline occurs not because the genetic code is changed, but because the DNA is chemically modified so that the lactase gene is switched off due to shut down of dietary influence. The epigenetic modification that turns off the lactase gene does not happen in lactose-tolerant individuals like your brother who constantly drinks milk. This observation is crucial in understanding how lactose intolerance develops with age.

Recent studies have shown that the symptoms of lactose intolerance can be alleviated in some people by changing the population of their intestinal microbiome by transferring lactose-digesting bacteria such as yogurt in them. The adaptation of the intestinal microbiome may explain why some ancient pastoral populations with no genetic evidence of lactase persistence tolerated milk and dairy products.

We think that giving lactic acid bacteria such as yogurt and fermented products regularly as a probiotic can ease the symptoms of lactose intolerance, because these bacteria may not persist in the colon. One promising new strategy is to give the lactic acid bacteria a complex sugar that they can digest but humans cannot for them to remain in the colon. But this needs to be studied.

Another way I can think of, is to use faecal microbiota transplantation (FMT) where a solution of faecal matter from a milk-tolerant donor is introduced into the intestinal tract of a non-milk tolerant recipient in order to directly change the recipient’s gut microbial composition to confer a health benefit to someone who is milk intolerant. That may be another good nutritional strategy we can work on.  

In summary, lactase deficiency is thought to be genetically programmed and age-related as the gene that is responsible for the production of lactase (LCT gene), becomes dormant progressively with time. It tends to appear between the ages of 5-20 years and may be prevented through epigenetic influence by regularly drinking milk.

As a last note, let me tell you that I too am milk intolerant if milk is drunk more than 500 ml in one sitting. Perhaps my ICT gene is still active by putting milk regularly in smaller quantities into my tea, coffee, and cocoa-based beverages, though slowed down and the lactase expressed is insufficient to deal with more than 25 g of lactose in 500 ml of pure milk if drunk in one go.     

I hope I have explained to you Sussie Chan

(A 3,297 worded answer in 10 pages)

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