Séminaire MARRAKECH -PROFESSIONNELS DE SANTÉ - OCTOBRE 2020

Even though people live longer lives, there have been more and more food products and degenerative diseases also called civilization diseases (cardiovascular diseases, diabetes and cancers…) in the last fifty years.

Diseases have long been defined by only one factor (a disease, a cause, a remedy).

Nutritional and functional medicine is different because it considers the complexe interaction of genetic and environmental factors in the etiopathogenesis of the disease.

It respects the person and the diversity of metabolisms. It is perfectly in harmony with Hippocate medicine precepts, in other words « food is the only medicine » and this is a medical breakthrough according to which our food is linked to our health.

 

TOPIC

We often talk about younger and younger people who are more and more addicted to sugar.

With an addiction that can be compared to drugs, sugar consumption has constantly increased. Indeed, a person used to consume 6 to 8 kilograms a year a century later, a person now consumes 35 kilograms a year.

Consequently, diseases such as diabetes, obesity and cardiovascular diseases have become epidemics.

Sugar is responsible for 35 million casualties a year. It could be compared to a serial killer !

So where does this addiction to sugar come from and how can we handle it ?

The intestinal system is based on synergic interactions between the immune system, microbiota and the mucous intestinal membrane.

Therefore, if one of these systems is unbalanced, the intestinal ecosystem will be disturbed. 

The microbiota is colonized with billions of bacteria and has an symbiotic relationship with it and has an essential role in maintaining its homeostasis. We will see how the intestinal ecosystem imbalance can lead to dysbiosis and low grade inflammation linked to eating disorders especially sugar craving.

We will also analyse the subtle mechanisms of sugary food addiction by activating the reward circuits. Finally, the role of micronutrition will be analysed.

DYSBIOSIS

 

1.    ORIGIN OF DYSBIOSIS

Dysbiosis is linked to the qualitative and functional alteration of the microbiota and is caracterized by the depletion of some bacteria (lost of diversity) and the rise of some others.

Dysbiosis come from genetic and environnemtal factors especially the diet, drugs and toxins (1).

Among the main environnmental factors involved in dysbiosis , let’s quote : 

• The industrial products which are poor in micronutrients.

• Overconsumption of high glycemic index food with the systematic addition of hidden carbohydrates in industrial food.

• The lack of vegetables : vegetables are needed for the development of good bacteria and for the butyrate synthesis : a short chain fatty acids made by the good bacteria whose role is to feed the colonic cells (2)  and to maintain the intestinal barrier function.

• The use of pesticids and pollutants which are mutagenic agents and disturb the microbiota.

• Overconsumption of saturated fat is responsible for the increase of inflammatory bacteria which leads to the metabolic endotoxemia (3) (4).

• The antibiotherapy : the prolonged use of antibiotics namely during childhood can be linked to the decrease of good bacteria and an increase of bad bacteria with negative effects on the intestine (5) (6).

• The hormonotherapy

• The lack of chewing

• Stress

2.  DYBIOSIS AND LOW GRADE INFLAMMATION 

Dysbiosis and food intolerance

The immune system depends on our microbiota and its balance is essential for perfect immunity.

Besides, 80 % of the immune system is located in the gut.

Its role is not only to defend our bodies but also to be tolerant towards the food we eat.

Dysbiosis will lead a lack of immune tolerance towards some food products. This mechanism is also called food intolerance which brings about immunoglobulins G. 

The symptoms of the food intolerance are first digestive and then provoke a low grade inflammation but also extradigestive symptoms like sugar craving at the end of the day.

As a consequence, they can be linked to :

·       A lack of bacteria diversity that is dysbiosis

·       Genetics

·       A lack of digestive enzymes

·       The early introduction of food for babies even if the immune system is not mature enough to tolerate it.

·       A lack of food diversity and the fact that food products have been altered by industrialisation (cooking..).

The food intolerance are also going to create dysbiosis and the other way round. 

Dybiosis and low grade inflammation

The intestinal mucous forms a barrier which separates the host of their outside environnment.

The microbiota protects the intestinal epithelium in particular on the thickness of intestinal mucous, the size of the intestinal villi and mucus production.

It therefore has a trophic role.

Dysbiosis and food intolerance added to a lack of chewing will make the intestinal membrane more fragile which is going to become more leaky and permeable.

This is what we call « leaky gut syndrom ».

If this membane is damaged, it will open the door to toxins and will lead to a bacterial translocation and thus a metabolic endotoxemia.

The inflammation is the immune response  when the barrier breaks and is going to bring about sugar craving as we will see in this second part.

 

THE ORIGINS OF SUGAR ADDICTION

Microbiota, gut, brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the vagal nerve.

There are between 500 to 600 millions neurons in the human enteric nervous system connected with microbiota.

Indeed, microbiota can produce all the neurotransmitters which can influence brain chemistry and food habits.

Disturbance of this system has been involved in eating disorders.

Understanding how dysbiosis affects brain chemistry is a key to understanding sugar craving because bacterial metabolites from the gut influence the regulation of the gut brain axis.

 

1.    DECREASE OF SEROTONIN AND SUGAR ADDICTION

The gut microbiota contributes to the regulation of food habits by influencing tryptophan metabolism. Tryptophan is an essential diet derived amino acid and is required for serotonin synthesis.

Serotonin is a monoamine neurotransmitter that regulates appetite, mood, sleep and sugar intake. Approximately 90 % of the human body’s total serotonin is located in the gastro intestinal tract. His synthesis starts around 4 pm till the evening.

 

A.     Lack of micronutrients and low serotonin synthesis

Micronutrients like tryptophan amino acid , vitamin B3, vitamin B6, iron and copper are needed for the serotonin production. Consequently, a lack of these micronutrients in somebody’s diet or a bad absorption due to leaky gut syndrom will decrease the serotonin synthesis.

B.     Decrease of serotonin and inflammation : kynurenine pathway

Once absorbed from the gut, tryptophan crosses the BBB (blood-brain-barrier) and participates in serotonin synthesis.

Dysbiosis, food intolerance, leaky gut but also stress will make the tryptophan divert towards the kynurenine pathway.

Consequently, serotonin will decrease.

Stress and low grade inflammation activate the tryptophan 2,3 dioxygenase enzyme TDO and the indolamine 2-3, dioxygenase IDO and favour the kynurenine pathway depriving the 5 HT pathway of tryptophan and reducing serotonin synthesis (7).

The neurotoxic metabolites of the kynurenine pathway will influence brain function and lead to sugar craving.

 C. Decrease of serotonin and competition with neutral amino acids

The serotonin synthesis is influenced by the tryptophan availability.

It is not plasma tryptophan alone which determines the amount of tryptophan available to the brain conversion to serotonin but rather the ratio of plasma tryptophan to the other neutral amino acids.

Tryptophan and the neutral amino acids compete for attachment to the same transporter (BHC) across the blood-brain barrier.

A carbohydrates intake will lead to insuline production and increase free tryptophan (not bound to albumin). This will increase its crossing through the BBB (blood-brain-barrier). 

The result will be an increase of brain tryptophan after a rich carbohydrates meal and an increase of serotonin synthesis (8) (9) (10).

Consequently, a decrease of serotonin due to a poor micronutrients diet, low grade inflammation, dysbiosis  and proteins-rich dinner can explain the sugar craving in the evening and also at night.

The other signs of this serotonin lack are the following :

People can feel blue, be withdrawn, be depressed, they can find it hard to go to sleep or they may wake up during the night. We have noticed that sugar craving linked to a decrease in serotonin can be even stronger in premenstrual syndrom.

One of the solutions to tackle this problem of sugar addiction will be to regulate the serotonin rate.

2.    CANDIDA ALBICANS AND SUGAR ADDICTION

Dysbiosis is going to lead to a development of candida albicans.

Candida albicans is a normal host of our gut. It is present in small quantities and is not detrimental to our health when it is maintain by good bacteria.

Many factors may explain the development of the candida to its abnormal (hyphae form) form, such as stress, dysbiosis, sugar consumption, food intolerance and a lack of chewing.

Candida needs carbohydrates for its development and it is going to create a form of sugar addiction linked to exorphins liberation which can cross the BBB and stimulate some areas of the hypothalamus involved in somebody’s appetite. The others symptoms are bloating, tiredness, digestive disorders and mood variations.

Candida albicans concerns about 40 % of the population. However, quite paradoxically it is not well known.

3.     . SUGAR ADDICTION VIA ACTIVATION OF REWARD CIRCUIT 

Scientists have shown that sugar can have an impact of somebody’s brain exactly like a hard drug.

Serge Ahmed, neurobiologist and researcher and director of the CNRS of Bordeaux university has proved that rats had a stronger craving for sugar than for cocaine.

The experiment has been done with laboratory rats in a cage. They had to choose between a dose of intravenous dose of cocaine on the one hand and sugary drink with saccharose on the other hand.

Among the one hundred rats that have done the experiment, 90 % have prefered the sugary taste than the drug effect. That may be explained by the fact that sugar even when it is hidden (in some industrial products for example) activates the reward and motivation circuit of the brain exactly like a drug.

When saccharose metabolised in fructose and glucose is eaten, it is supposed to activate the dopaminergic neurons thus influencing our sensory preferences (11), (12).

Decrease reward sensitivity

The more we eat sugar, the more we crave for sugar.

Overconsumption of sugar induces a dysfunctioning of reward circuit similarly to those observed in drug addicts but also a decrease of reward sensitivity. (13) (14). 

4.    LEPTIN RESISTANCE

Leptin is an hormone that helps manage appetite. Its produced by the fat cells and helps to control metabolism and hunger. Multiple factors such low grade inflammation and stress contribute to leptin resistance (15). The leptin resistance is defined by the reduced ability of leptin to suppress appetite. This will increase the food intake including sugar.

5.    INSULIN RESISTANCE

Low grade inflammation will lead to an insulin resistance and so insulin can not play its role.

Due to hyperinsulinism, the reserves are not accessible, which can lead to an increase in carbohydrates intake due to a lack of energy.

 TACKLING THE ISSUE VIA MICRONUTRITION

Based on the rebalancing of the microbiota, one of the strategy will consist in modulating the inflammation and improve the patient’s nutritional and micronutritional environment.

1.    MICRONUTRITION

A.    REBALANCE THE INTESTINAL  ECOSYSTEM WITH PROBIOTICS

Many therapeutics strategies are used to restore intestinal eubiosis but the most adopted therapeutic strategy consists in the administration of probiotics.

The probiotics are « live microorganisms that, when administered in adequate amounts, confer a health benefit on the host » (international scientific association for probiotics and prebiotics).

The role of probiotics consists in : 

Restoring the microbiota with a sufficient amount of good bacteria from known strains and eradicating the pathogens including candida proliferation (16).

The benefits of probiotics on health of the host can only be attributed to specific strains that have been the object of studies and cannot be extrapolated to other strain that have not been studied.

The ideal qualities of a probiotic is to be resistant to gastric environment (bile and pancreatic), adhering to the entherocytes, optimizing the host’s immunity, producing bacteriocins, should belong to species that form normal components of our gut microbiota and be safe.

Lactobacillus acidophilus NCFM strain has proved particularly effective and has a good adhesion to the entherocytes (17)(18) (19) (20) (21) (22).

It has been shown that lactobacillus acidophilus NCFM improve symptoms of bloating and preserve insulin sensitivity (23) (24).

Moreover, the Lactobacillus acidophilus NCFM could limit the increase of the candida albicans and modulates mu-opioids receptor expression and activity and thus could modulate the pain sensation (25).

Somes probiotics like bifidobacterium HN019 enhances the immunity and could be effective to rebalance the microbiota (26).

Combine saccharomyces boulardii with probiotics

Saccharomyces boulardii is a nonpathogenic yeast which can be effective against candida albicans development (27), (28), (29). 

B.    OPTIMIZING THE TIGHT JUNCTIONS

The second strategy will be to repair the tight junctions of the intestinal barrier.

L glutamin and zinc intake : “RÉGÉNÉRATION INTESTIN” COMPLEX

When a patient suffers from metabolic stress, glutamin is used in immune system and this brings about a depletion of its concentration on the intestinal cells thus disturbing the integrity of the intestinal barrier.

Glutamin is used as a fuel for intestinal cells so as to regenerate them.

It will be needed for repairing tight junctions of the gut (30). 

The lack of zinc will contribute to the leaky gut syndrom and it is proven that zinc improves the intestinal barrier and will therefore prove useful. (31) (32).

Vitamin D and vitamin A

Vitamin D is a key hormon for our health.

It is going to play an important role with vitamin A in maintaining gut barrier function by regulating the expression of tight junction proteins on intestinal cells (33).

Quercetin

Quercetin enhances intestinal barrier function and restore tight junctions (34).

C.    OPTIMIZE THE MEMBRANES FLUIDITY AND MODULATE INFLAMMATION,

 Vitamine D

Vitamine D has a suppressive role on autoimmunity and antiinflammatory effect.

It has been shown that a deficiency of vitamin D could predispose to more intestinal injury.

Indeed, Vitamine D induces regulatory T cell differenciation in the mucosal tissues and reduces inflammatory cytokines secretion.

Vitamine D supplemention will be used for its protective role on mucosal barrier homeostasis and for its immunomodulating property (35) (36) (37) (38).

 Curcumin

Curcumine prevents nuclear factor KB activation which is largely involved in inflammation process.

Moreover, curcumin decreased level of pro inflammatory cytokines and protein kinases.

Thus, Curcumin will be used for its anti-inflammatory properties (39).

n-3 polyunsaturated fatty acids (PUFAs) SUPPLEMENTATION

Neurones are rich in n-3 polyunsaturated fatty acids (PUFAs) which are involved in the structure of most lipids including those in the nervous system.

n-3 polyunsaturated fatty acids (PUFAs) are highly abundant in brain tissue and mitochondria and participate in the membrane fluidity. This is an important point for a good neurotransmission. 

n-3 polyunsaturated fatty acids (PUFAs) supplementation or n-3 rich diet will improve the tryptophan crossing through the brain (40) , the insulin and leptin sensitivity.

As we have shown, low grade inflammation induces resistance to leptin.

The Leptin receptors are located in the hypothalamus. 

A good membrane fluidity will be needed for the crossing of leptin through the brain and thus its fixation on its receptors.

Insulin resistance is linked to inflammatory pathways and a good mitochondrial membrane integrity is required for insulin signalling. n-3 polyunsaturated fatty acids through their anti inflammatory effects will improve insulin sentivity (41) (42) (43) (44).

D.    5HTP AND GRIFFONIA SIMPLICIFOLIA SUPPLEMENTATION 

Griffonia simplicifolia

The seeds of the plant Griffonia simplicolia are used as a herbal supplement for their 5 hydroxytryptophan (5HTP) content. It has been shown that the 5HTP present in griffonia extract increases the feeling of satiety and decreases the BMI (body mass index) in overweight women (45).

Moreover 5HTP leads to a reduction of meal size.

Another study brings out a significant weigh loss in 5HTP treated patients and a reduction in carbohydrate intake as well as a consistent presence of early satiety  (46) (47).

Rhodiola rosea extract

Rhodiola rosea plant has anti-inflammatory properties and can strenghten normal physiological functions such immunity. Moreover, it can prevent chronic stress (48).

Thus, rhodiola rosea extract could improve sugar craving management when combined with griffonia extract.

E.     IMPROVE THE NUTRITIONAL STATUS OF THE PATIENT

Control and correct micronutrient deficiencies, including those necessary for the synthesis of serotonin: tryptophan, iron, copper, B3 and B6 vitamins.

F.   IMPROVE THE DETOXIFICATION PROCESS by adding N-acetyl cysteine, artichoke, B vitamins, radish, glycine supplements.

G.    OPTIMIZE MITOCHONDRIAL FUNCTION and provide nutrients that protect mitochondria from oxidative stress such as CoQ10, vitamin E,C, n-3, alpha-lipoic acid, B vitamins, L carnitin.

2.    DIET

A.     AVOID FOOD INTOLERANCE

Food intolerance can cause inflammation and can be detected either by the principle of suppression/reintroduction of certain foods over a given period, or by a blood test of food intolerance.

B.     CANDIDA DIET

Avoiding certain foods that increase the development of candida, such as yeast, chocolate, sugar, vinegar, alcohol.

C.     IMPROVE TRYPTOPHAN AVAILABILITY 

Consuming a carbohydrate rich and protein poor meal increases brain levels of tryptophan and serotonin.

Thus, the ratio tryptophan/ neutral amino acids must be higher in dinner than at noon.

Avoiding protein-rich meals in the evening and promoting a small amount of good carbohydrates may be a good strategy to improve the availability of tryptophan and serotonin synthesis (49) (50).

In addition, it can be improved by a fruit consumption in the late afternoon.

D.    MEDIATE INFLAMMATION THROUGH DIET

 omega 3 rich diet : eat sardines, mackerel, nuts

Arachidonic acid derived eicosanoids modulate the expression of proinflammatory and immune cytokines.

Overproduction of these cytokines is associated with chronic inflammation.

It has been proven that n-3 polyunsaturated fatty acids (PUFAs) EPA (eicosapentaenoic acid) and DHA ( docosahexaenoic acid) found in fish oils suppress the production of arachidonic acid.  Thus, an n-3 polyunsaturated fatty acids rich diet can alter pro inflammatory cytokines production.

AA/EPA Ratio : The ratio acid arachidonic/n-3 is correlated to the inflammation response and n-3 turn out to be an effective strategy to tackle the arachidonic acid effect dealing with inflammation.

Prebiotics (fructo oligosaccharides)

Prebiotics are needed for a balanced microbiota.

Adding prebiotics to the diet as high fiber foods, fruits, vegetables, whole grains is essential for the synthesis of short chains fatty acids which will inhibit the growth of bad bacteria and promote eubiosis. 

Besides, it has been proved that a rich prebiotic diet may increase the leptin sensitivity and so regulate the satiety mechanisms (51).

The importance of chewing : a lack in chewing can lead to a bad digestion and a low grade inflammation.

It will be recommended to chew food enough.

It would be advised to limit the consumption of red meat to use antibiotics only when it is necessary, to avoid anti acids and pesticids, and to not eating big food quantities.

 

CONCLUSION

 Studying the intestinal ecosystem and nutritional status of a patient is an essential prerequisite for understanding the sugar addiction mechanisms and how to deal with this issue.

More and more evidence prove the hypothesis according to which our food habits are influenced by microbiota and reveal its real psychobiotic effects (52).

Microbiota can be considered to be a real organ that communicate with brain via the vagal nerve and its regulation constitutes a key step in tackling the issue of sugar addiction.

Indeed, dysbiosis can create sugar addiction and altering tryptophan which is the precurseur of serotonin.

Besides, there are more and more products with high glycemic index which may be the link of an irrational behavior with sugar via the activation of neurons of reward and pleasure.

The eubiosis and dysbiosis condition of the gut influences our healthy and disease status and a balanced microbiota is a necessary first step for being healthy.

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