NUTRITION AND GENE

(AHD 2113)

Title:

Islamic Perspective on Nutrigenomic intervention in

Postmenopausal Osteoporosis (PMO)

Members:

Aneeesah Binti Abd Rashid (1219540)

Jamilah Binti Ghazali (1215274)

Alhafizah A. Ramos (1215382)

Khairun Nabila Binti Rosli (1213338)

Ainul Hanani Binti Mohd. Yusoff (1210168)

Lecturer:

Dr. Muhammad Bin Ibrahim

Date Submitted:

29 October 2013

1. INTRODUCTION

Bismillahirrahmanirrahim

Nutrigenomics is the study of the effects of foods and food constituents on gene

expression. It is about how our DNA is transcribed into mRNA and then to proteins and

provides a basis for understanding the biological activity of food components. The boundary

between health and disease is often defined by a complex equilibrium between two elements,

genetics and lifestyle. The aim of nutrigenomics is to personalize nutrition and its effects on

health by tailoring food to the individual genotype.

The purpose of this review is to present the interaction between a genetic polymorphisms

disorder which is Post-Menopausal Osteoporosis (PMO) and diet. Poor nutrition can be risk

factor for diseases. Common dietary chemicals can act on the human genome, either directly or

indirectly to alter gene expression or gene structure. The degree to which diet influences the

balance between health and disease depends on an individual‟s genetic makeup.

Osteoporosis is characterize by weaken of bone due to decreasing bone density mass as it

become more porous and less packed. This will increase the risk of bone fracture. After the age

of 35, the bone density starts decreasing and become more rapid in women for several years

following the menopause due to decreasing of hormone estrogen. Many factors, including age,

physical activity, diet, and pharmacologic treatments, influence the risk of PMO, but one of the

most clinically important risk factors is a family history of the disorder. As in other polygenic

disorders, alterations in numerous genes each make small contributions to susceptibility to

osteoporosis.

According to a study, at least 56 genes involved in osteoporosis and fracture risk had

been identified. Currently, several nutrition related issues benefit from genetic research. A

number of conditions like bone loss in post-menopausal women shows the influence of genetic

variation on nutrition advice. In this topic, we aim to identify some gene variations that have a

greater influence on the development of bone problems and we can then make recommendations

which may reduce or eliminate these problems.

Nutrigenomic is an exciting promising field with numerous benefits to explore. Smallest

unit in the body like DNA can make a big contribution to the body. This proves the greatness of

Allah. Off course, human can theorize all they want, and debate everything they want, yet still

we have to admit that only God knows the real truth as He is the ultimate Creator of all.

2. PROBLEM STATEMENT

The prevalence of PMO has been increased nowadays. It is estimated that 50% of women

suffer a fracture after the age of 50 years. Since the human genome had been discovered and

mapped, scientist found that there is actually a strong relation between genes in human body and

food consumption among individuals. It is called nutrigenomics. The variation in gene that make

human a bit different with the other is call polymorphism. Even the susceptibility of an

individual to PMO is somehow affected by gene. Thus, in this paperwork we would like to

discuss on how the nutrigenomic can improve the PMO diet intervention and how far it can be

beneficial to the patient.

3. NUTRITION, GENETICS AND POLYMORPHISM

3.1 Definition Of Nutrigenomics

The term "-genomics" represents the mapping of genes. Nutrigenomics is the study of

food and nutrition focused mainly on the interactions with diseases and human-specific genes. It

is a study of the effects of foods and food constituents on gene expression. Nutrigenomics is

about how our DNA is transcribed into mRNA and then to proteins and provides a basis for

understanding the biological activity of food components.

Nutrigenomics has also been described by the influence of genetic variation

on nutrition by correlating gene expression or single-nucleotide polymorphisms with a

nutrient‟s absorption, metabolism, elimination or biological effects.

Nutrigenomics aims to develop rational means to optimise nutrition, with respect to

the subject‟s genotype. It tries to explain what is the effect of some nutrients have, on a person

and helps to understand which food to choose for a long, healthy and vital life. By taking this

approach we can achieve optimum nutrition and satisfy the individual needs of each one of us.

3.2 What Is Polymorphism?

Polymorphism is a natural variation in a gene, DNA sequence, or chromosomes that have

no adverse effects on the individual and occur with fairly high frequency in the general

population. Genetic variations occurring in more than 1% of a population would be considered

useful polymorphisms for genetic linkage analysis.

Polymorphism involves one of two or more variants of a particular DNA sequence. The

most common type of polymorphism involves variation at a single base pair. Polymorphisms can

also be much larger in size and involve long stretches of DNA. Called a single nucleotide

polymorphism, or SNP (pronounced "snip"), scientists are studying how SNPs in the human

genome correlate with disease, drug response, and other phenotypes. Postmenopausal

osteoporosis (PMO) is one of the examples of polygenic disorder due to the polymorphism

that affect both bone formation and bone resorption.

Allah swt had mentioned in Surah Fussilat, verse 53:

“We will show them Our signs in the horizons and within themselves until it becomes clear to

them that it is the truth. But is it not sufficient concerning your Lord that He is, over all things, a

Witness?”

Based on this verse, it has been proven that, in our creation, there were many signs that Allah

wants us to discover and study to make us more nearer to Him.

4. POST-MENOPAUSAL OSTEOPOROSIS AND GENES RELATED

4.1 What is Post-Menopausal Osteoporosis

Osteoporosis is characterize by weaken of bone due to decreasing bone density mass as it

become more porous and less packed. This will increase the risk of bone fracture especially in

the wrist, hip, and backbone. Other part of the body can also affect if self-care are ignore. Bone

density mineral especially the density of calcium in the bone keep increasing until mid-20s. After

that the growth of bone and bone density keep plateau until the age of 35 before it starts losing. It

became more rapid in women for several years following the menopause and can lead to

osteoporosis. This is call as post-menopausal osteoporosis (PMO).

PMO has the fastest onset, with as much as 20-30% cancellous and 5-10% cortical bone

lost immediately after menopause, due to the sudden drop in ovarian hormones. It is estimated

that 50% of women suffer a fracture after the age of 50 years. Of particular concern is the fact

that 18% of hip fracture patients are dead after 3 months. Having osteoporosis does not

automatically mean that the bones will break, it just means that the affected people have a

„greater risk of fracture‟. Thin, fragile bones in themselves are not painful but the broken bones

that can result, can cause pain and other problems. Osteoporosis does not generally slow or stop

the healing process. Bones that break because of osteoporosis will still heal in the same way as

they do in people who do not have osteoporosis, which is usually about six to eight weeks.

Fractures from osteoporosis are more common than heart attack, stroke and breast cancer

combined. Many factors, including age, menopausal status, smoking, physical activity, diet,

coexisting diseases, and pharmacologic treatments, influence the risk of PMO, but one of the

most clinically important risk factors is a family history of the disorder. As in other polygenic

disorders, alterations in numerous genes each make small contributions to susceptibility to PMO.

4.2 Genes That Responsible For the Susceptibility of PMO

There were numerous studies had been carried out to determine the gene that responsible

to the susceptibility of PMO. In 2012, a research team led by Dr. Seung Hoon Lee took part in a

multinational genome research project identified at least 56 genes involved in osteoporosis and

fracture risk. The journal was published on April 16th in Nature Genetics. One of the genes

identified is WNT1, an important ligand in the regulation of bone mass. WNT signaling is

essential for normal skeletal development and homeostasis. It induces osteoblast differentiation

and bone formation. Mutation in this gene can cause early onset of PMO and increase chance of

bone fracture due to abnormal bone formation.

Other important gene involve in bone formation is Collagen 1, alpha 1 (COL1A1). It is

the primary protein matrix used for bone synthesis. Polymorphisms of the COL1A1 gene can

lead to reduced collagen formation, which in turn can lead to reduced bone mineral density

(BMD) and thus an increased risk of PMO in later years. Vitamin D receptor (VDR) gene is also

another gene that found out to be very crucial in strengthening the bone. It increases the action of

the vitamin D receptors for efficient absorption of calcium from the gut. If the VDR gene

encounters polymorphism, it can reduce the action of the vitamin D receptors, which will

compromise the absorption. There is an association between VDR gene allelic variation and

BMD. Low BMD suggests an increased tendency toward PMO.

All these genetic variation occur in genes that responsible in bone formation and

maintenance can be identified in an individual by genetic risk assessment test. A simple genetic

test using a blood sample could identify women at elevated risk for developing PMO

comparatively early in the course of the disease. This allows the women and their physicians to

pursue risk reduction practices and would enable nutritional or therapeutic intervention at an

early stage, so that bone loss and fractures are minimized or prevented.

5. DIET INTERVENTION FOR POST-MENOPAUSAL OSTEOPOROSIS

ACCORDING TO A FEW GENE POLYMORPHISM

5.1 COL1A1 gene

Polymorphism of the COL1A1 gene can lead to reduced collagen formation, which in

turn can lead to reduced bone mineral density (BMD) and thus an increased risk of osteoporotic

fracture in later years. However, based on one study, it have been found that such T/T individual

(homozygous T alleles of COL1A1 genes) with a low calcium intake had low bone mass density

In short, having polymorphism in COL1A1 plus with diet that low in calcium can abruptly

increase the risk of low BMD. Thus, it is suggested patient with variation in COL1A1 gene

should increase the intake of calcium above RNI of normal people.

We are familiar with this verse “O ye who believe! Eat of the good things that We have

provided for you, and be grateful to Allah, if it is Him ye worship” (al-Baqarah: 172) that warn

us to eat „good‟ things. In this cases, good can be precise in term of nutrients – specifically

calcium. As we know, calcium is the cornerstone of strong bones. The pop star of calcium is

undoubtedly milk and dairy product. However, many people dislike consuming milk and the

dairy product due to its taste. It is seems related to Quranic verse from surah Al-Baqarah verse

216, “…perhaps you hate a thing and it is good for you, and perhaps you love a thing and it is

bad for you. And Allah knows, while you know not”. Calcium is very important to increase the

BMD during growth period (born-20 years). A single 8 ounce cup of milk whether skim, low fat

or whole has 300 mg of calcium. A cup of yoghurts has at least as much calcium as 8 ounce cup

of milk. Even if lactose intolerance, choose lactose-reduced or lactose free dairy product as

removing lactose has no effect on the calcium contents.

However, if patient keen to avoid dairy products, there are another solution such as

consume fish with edible bones such as tinned sardines. All those little fish bones have just what

patient need to build mass in his/her body. Eating 3 ounces of canned sardines delivers a little

more calcium than a cup of milk. Besides that, broccoli and dark leafy greens vegetable like kale

and turnip green has plenty of calcium too. One cup of chopped, cooked turnip greens has about

200 mg of calcium. If patient resist eating, they can try calcium fortified foods, which the

product do not naturally contain calcium but have been enhance with calcium. Fortified orange

juice has up to 240 mg of calcium and fortified cereals deliver calcium up to 1000 mg per cup.

Next is soy food, half of a cup-enriched tofu contains as much as 861 mg of calcium.

Plus, soy products also come with isoflavins, the chemical that claim to give benefit to

postmenopausal women since it is estrogen-like. Besides that, nuts and seed also can booster

bone health in several ways. Walnut and flaxseed, rich in omega 3 fatty acids. Peanut and

almond contain potassium, which protect again calcium loss in urine. Nuts also contain protein

and other nutrient that play a supportive role in building strong bones. However, if patient is

really lack of calcium, the last resort is given calcium supplementation namely calcium

hydroxyapatite, as this include type one collagen protein and has been shown to help prevent

PMO. Supplement is easy way to boost calcium intake but not taken it overdose, as it will lead to

kidney stones.

5.2 VDR gene

Polymorphism of VDR gene, homozygous for vitamin D3 receptor polymorphism

reduces the action of vitamin D receptor, which compromise absorption of calcium from gut. So,

sometimes dietitian will come out with supplementation above the reference nutrient intake

(RNI) to prevent impaired of calcium absorption due to VDR polymorphism. Other steps are to

reduce or avoid foods which can impaired calcium absorption and increase calcium excretion

such as caffeine, because caffeine leaches calcium from bones, sapping their strength. In fact,

roughly 6 milligrams of calcium is lost for every 100 milligrams of caffeine we ingest. While,

cola and soda drinks contain phosphoric acid, a food additive that appears to weaken the

intestines and the absorption of calcium.

Besides that, patients need to observe the bean they wish to include in their diet. Pinto

beans, navy beans, and peas are high in substances called phytates. Phytates can interfere with

the body‟s ability to absorb the calcium that‟s also found in the beans. But that does not mean

that they must exclude bean in the diet. Beans are rich in magnesium, fiber, and other nutrients,

consuming them are still good for osteoporosis prevention. They can simply reduce the phytate

level by soaking beans in water for a few hours and then cooking them in fresh water.

Moreover rich green raw spinach and Swiss chard contain bone-healthy calcium and

many other vitamins and minerals. However, they contain substances called oxalates, which can

bind up the calcium and make it unavailable to the body. To enjoy the other health benefits of

these vegetables such as the vitamin and mineral without compromising the calcium absorption,

patient must balance these veggies with other foods that contain calcium that readily absorbed by

the body. Try to relate with this verse, “O children of Adam! attend to your embellishments at

every time of prayer, and eat and drink and be not extravagant; surely he does not love the

extravagant” (al-a‟raf : 31), we should eat to the extent of the food can give optimal benefit to

use, do not over consumption until the food can be harm instead provide good nutrition and fill

our stomach.

In addition, the more salty foods we eat, such as processed foods and condiments, the

more bone-strengthening calcium we lose. It is because salt is known to cause excessive calcium

excretion through the kidneys. So, limit the salt intake and use tasty herbs and spices instead.

Furthermore, patient needs to improve blood sugar control by adopting a low-glycemic index

way of eating. Excess sugar inhibits calcium absorption and depletes phosphorus, another

mineral important in facilitating the absorption of calcium. Last but not least, alcohol chronic and

heavy alcohol consumption is known to contribute to low bone mass, decreased bone formation,

and increased incidence of fractures, and delayed fracture healing. As muslim, we already given

the answer regarding this issue in surah Al-Baqarah verse 219 “They ask you about wine and

gambling. Say, "In them is great sin and [yet, some] benefit for people. But their sin is greater

than their benefit." And they ask you what they should spend. Say, "The excess [beyond needs]."

Thus Allah makes clear to you the verses [of revelation] that you might give thought." Allah

knew that alcohol is very harmful to our body so He prohibits it to us.

The diet intervention is very critical in disease prevention or management. Based on our

knowledge on the gene polymorphism and it relation to bone development and maintenance, we

are able to improve and tailored the diet planning as to obtain better PMO treatment. However,

there are still big uncertainties in this way of diet intervention because Allah‟s knowledge is

unlimited and ultimately huge. Thus we need to continuously make effort, and seek the

knowledge, but after all, back to Allah as stated in surah at-Talaq verse 3 “And will provide for

him from where he does not expect. And whoever relies upon Allah - then He is sufficient for

him. Indeed, Allah will accomplish His purpose. Allah has already set for everything a [decreed]

extent.”

6. HOW NUTRIGENOMICS BENEFITS THE PMO PATIENT?

Poor dietary choice within a sedentary lifestyle is contributing to chronic ill health. The

“one-size-fits-all” strategies in public health have not always been delivered consistently, which

may be why they do not appear to be working and changing people‟s dietary habits. However,

personalising nutrition may be more effective in achieving the desired long-term change.

Nutrigenomics can benefit for the individual with the risk of PMO as a preventive health effects.

As an individual undergo the genetic screening, we can determine whether she has the risk of

getting PMO. When the specific markers have been identified, a personalized diet can be

suggested to prevent PMO. The risky individual will be advice to increase the calcium intake by

fish with edible bone (tinned sardine), dark leafy greens, broccoli and seeds as a preventive

action.

In addition, nutrigenomics will provide opportunities for the development of food

products or dietary advice tailored to the nutritional needs of specific groups of consumers, or

even individuals who were in the risk of PMO. The specific food products will occupy the

necessity dietary intake of PMO risk group. Industry needs strong examples with clear benefits

to put nutrigenomics products on supermarket shelves. Lifestyle products such as organic and

free-range demonstrate consumers‟ desire for personalised products that suit their ethical

consciousness as well as their perceived dietary needs such as high calcium with restricted

amount of wheatgerm for PMO risk group. Phenotypic products (calcium hydroxyappatite),

which are clinically proven to different extents, are targeted those consumers that know they are

at risk of PMO due to the fact that they have PMO in family history or they have a less than ideal

lifestyle.

On the other hand, discovering genetic susceptibilities can be a strong motivator for

making dietary and lifestyle changes. It is not only a motivator for the screened person, but also

to other people. As someone know that she has the risk of PMO, she will be more concern and

aware of her dietary intake. She will also change her lifestyle for good. These behavioural

changes may lead to extended life span.

Besides, with nutrigenomic studies, unnecessary vitamins and other dietary supplements

can be avoided. Many of us tend to take dietary supplements unnecessarily without knowing

what is the actual amount needed by our body. Not only it can waste our money, excess intake of

supplements can also cause toxicity to us. Therefore, nutrigenomic is vital for us to know the

specific supplement which is necessary according to our gene mapping.

Moreover, nutrigenomics can let people whose health is relatively unaffected by diet can

continue to eat foods that they enjoy. For example, a person that already confirm has silent PMO

risk genes, they can enjoy eating foods without certain restriction such as caffeine intake which

can increase calcium excretion.

There were a lot of benefits that we can gain through nutrigenomics study. However, our

knowledge in this field was still limited and need further discovery and researches. As Allah said

in Surah Al-Baqarah, verse 30, “I know that which you do not know.”

7. CONCLUSION

Nutrigenomics is a discovery science which aims at understanding how nutrition

influences metabolic pathway and homeostatic control and how this regulation is disturbed in the

early phase of a diet-related disease. Nutrigenomics contribute many benefits to human. It is one

of the new science fields that have emerged and able improve public health. This field is needed

to be discovered, explore and do more research as it give many advantages to human health.

Post-menopausal osteoporosis (PMO) is a polygenic disorder, occurs due to the reduction

of bone mass in an individual. Research has shown that poor nutrition and lifestyle add to the

risk of bone problems in people carrying specific variants of genes related to osteoporosis. By

incorporating good diet and lifestyle recommendations, individuals can improve their bone

health at any stage in their life.

Nutrigenomic can benefits for the individual with the risk of PMO as a preventive health

effects. In order to prevent PMO, a personalized diet can be recommended if the specific markers

have been identified. The risky PMO individual is advices to increase calcium intake as a

preventive action because prevention is better than cure. Besides that, discovering genetic

susceptibility can be a good motivator for making dietary and lifestyle changes. This behavioral

change may lead to extended lifestyle. We will be more concern and aware of our dietary intake.

PMO risky individual needs to change their dietary intake and lifestyle to stay in a healthy

condition status.

In the late century, scientist did not found yet that diet and environment can influence the

gene expression. Now, they know that thousands of substances in foods impact the genes either

promoting or suppressing specific gene expression. In chapter al-Alaq verse 1-5, Allah asks us to

seek knowledge in this life. “Recite in the name of your Lord who created. Created man from a

clinging substance. Recite, and your Lord is the most Generous. Who taught by the pen. Taught

man that which he knew not”. Muslims need to be knowledgeable community and be more

proactive in acquiring knowledge as it is the commandment of Allah SWT. We need to be an

extraordinary Muslim to show that Muslims are at the number one in education level.

The great challenge of the 21st century will be to integrate the scientific understanding

and provide diet, lifestyle and drug recommendations to the individual to maintain health and

prevent diseases rather than simply develop diagnostics and drugs to identify and attempt to cure

them once they have emerged. Nutrigenomic is still in its infancy stage. There are still many

uncertainties revolve around and there are still many hypothesis that did not come out yet with

conclusion. “Say: if the sea were to become ink to record the Words of my Lord, indeed the sea

would be all used up before the Words of my Lord are exhausted, and it would be the same even

if We were to bring an equal amount of ink” (al-Kahfi:109). This verse shows that knowledge is

infinite and unlimited.

Today with the advance of technology, it changes people life either to be better person or

vice versa. It is depends on how we receive and implement the knowledge that we get. The

important thing is the expanded knowledge can provide a reminder and reflection to human in

believing that everything comes from the Mega-Power. He gives strength to people to think,

work and create something. Only individuals who are thinking will be able to recognize and

understand and accept with sincere hearts. Everything may not happen because of chance,

natural or natural phenomena but it comes from the Great Power who is Allah.

REFERENCES

Fernando Rivadeneira, pp 491-501. Retrived October 27,2013 from

http://www.nature.com/ng/journal/v44/n5/full/ng.2249.html

Osteoporosis Facts & Statistics. Retrieved October 27, 2013 from

http://www.osteoporosis.ca/osteoporosis-and-you/osteoporosis-facts-and-statistics/

J. N. Hirschhorn, G. Luigi ,N E. J Med. 2008. 2403-2405. Bona Fide Genetic Associations with

Bone Mineral Density. Retrieved October 27, 2013 from

http://www.nejm.org/doi/full/10.1056/NEJMe0803046

What is osteoporosis? National Osteoporosis Society. Retrieved October 27, 2013 from

http://www.nos.org.uk/page.aspx?pid=247

BMJ, 1996;313:960.3 Genetic test for osteoporosis,

Retrieved October 27, 2013 from http://www.bmj.com/content/313/7063/960.3