In our previous issue we briefly mentioned that the date fruit facilitates delivery and can be eaten to help prevent infertility. This article will continue to examine their manyfold health benefits with a specific focus on their protective features against many diseases.

All essential amino acids

Dates contain 18 of the 20 amino acids found in living creatures. We may sort the quantity of amino acids found in dates from highest to lowest as: Glutamic acid, Aspartic acid, Leucine, Proline, Arginine, Phenylalanine, Valine, Alanine, Serine, Glycine, Iso-leucine (800 times more than an apple), Lisin (2000 times more than an apple and banana), Threonine, Histidine, Tyrosine, Methionine, Cysteine and Tryptophan.

Dates contain all of the 8 essential amino acids that should never be neglected in nutrition and are not made in the body. Additionally, the fact that dates offer 10 non-essential substances that can be made in the body means that all the necessary materials for the synthesis of these proteins, which serve as the basic building blocks of the human body, are present in dates. In this sense, date is a very unique fruit, and this is why a human being could survive on only dates and water for years. V. H. W. Dowson, one of the renowned experts on this subject, says that a date and a glass of milk will be enough to meet a person’s daily nutritional needs.

Other fruits are generally poor in protein while dates provide protection of the body against diseases and infections by providing amino acids, proteins, a renewal of cells, and a balance of body fluid. Meat is also useful for the body, but it may not be as useful as dates, especially during pregnancy. As a matter of fact, excessive consumption of meat in such a period may cause poisoning in the body. A diet consisting of light vegetables and fruits, such as dates, is more suitable.

A store of elements and amino acids

Dates contain more than 10 elements that are vital for keeping the human body healthy and fit. A hundred grams of dates contains 65 mg calcium, 521 mg potassium, 20 mg magnesium, 72 mg phosphorus, 2.69 mg iron, 0.06 mg sodium, 0.05 mg copper, 0.06 mg zinc, 0.07 mg manganese, sulfur, chlorine, and selenium as well as other elements that are very important for metabolic processes in the human body. Some studies have reported that the amount of minerals found in dates is three to five times higher than those found in apples, bananas, oranges, and grapes. Sodium and chlorine are effective in the activity of the muscular and nervous systems, in adjusting appetite, and protecting the body from gaining weight. They also take part in regulating the pH level in our blood and the water in the body. Sulfur is part of the amino acids cystine and methionine and is involved in the synthesis of many proteins.

In addition, potassium helps transport oxygen to the brain as a result of which we have clarity of thought. Moreover, it provides alkaline (basic) features that are suitable for body fluids. It stimulates the kidneys to remove toxic body waste, and additionally helps to lower high blood pressure and ensure the formation of healthy skin. Calcium and phosphate are essential minerals for muscles and healthy bone development, whereas magnesium is required for the kidneys and energy metabolism. Iron is necessary for the production of hemoglobin in the red blood cells. A person can meet the need for magnesium by eating 2-3 dates a day, and iron by eating 15 dates a day. These amounts will also prevent anemia.

Having been wisely created as a host of so many substances, dates surely have healing features. Numerous studies have been carried out on its feature of terminating harmful “free radical” molecules as well as its antioxidant, antimutagenic, anti-microbial, anti-inflammatory, antihyperlipidemic (anti-greasing) effects. Many studies have been done on the protective immune stimulating effects of dates against the stomach, liver, kidney diseases, and cancer. There are also other studies on the benefits of the seeds, pollen, leaves, and syrups of dates.

Antioxidant activity

In studies of its antioxidant effects, the date fruit has been shown to reduce oxidative stress that damages cells. The protective effect of high levels of vitamin C, A, E, and phenolic substances acts as a powerful antioxidant by accelerating the activity of enzymes such as catalase, glutathione reductase and glutathione S-transferase [1].

Anticancer effect

The components of a date have been found to initiate an antitumor activity. Research found that date juice stops the melanoma cell that causes epithelial colorectal adenocarcinoma, which is a type of intestinal cancer and a type of skin cancer [2].

Effects on diabetes, raising of glucose and fat in blood

The glycemic indices of the sugars in dates are as follows: Maltose (105), Glucose (100), Sucrose (68), Lactose (46), and Fructose (23). Their absorption rate by the body is also different. Glucose is absorbed fastest while fructose is absorbed later. These absorption and glycemic index differences show that dates do not raise blood sugar fast and provide an increased feeling of fullness and are a food that can be used easily for diabetics. They do not raise blood sugar rapidly thanks to the fact that the total glycemic index of a date is 39. This may be due to its minerals, phenolic, and phytoestrogen components. Magnesium plays an important role in regulating and secreting the effect of insulin. Zinc, on the other hand, stimulates the production and release of insulin while strengthening the effect of chromium insulin. Selenium has also been shown to promote glucose uptake.

Phenolic compounds delay the absorption of carbohydrates, preventing the rapid rise of sugar in blood. In scientific literature, the antidiabetic effect of dates have been proven. Lab studies have shown that a-glucosidase and a-amylase were suppressed, thereby delaying digestion and absorption of carbohydrates and normalizing glucose levels in plasma. The effect of date leaves, hydro-alcoholic extract and aqueous solution of seeds are also shown. In another study,[3] scientists treated diabetic rats by giving each rat 10 ml of reconstituted date seed powder per day. It was then observed that the serum glucose, cholesterol and triacylglycerol levels of rats returned to normal values.

Anti-inflammatory activity

There is a great deal of research on the anti-inflammatory effects of dates, expediting wound healing processes, and protecting the heart. Al-Qarawi et al. found that the juice obtained from dates is effective in improving the severity of gastric ulceration and reducing histamine and gastrin concentrations. According to the authors, the anti-inflammatory properties of date extract can be explained by its antioxidant effect [4]. In another study conducted on dates grown in Algeria, it was shown that the extract given orally produced a significant reduction in wound edema in Swiss albino mice. Presumably, this effect is due to the suppression of inflammatory cytokine enzymes that can interfere with prostaglandin synthesis of some active substances in date sap.

Antimicrobial activity

There are a lot of studies about cold pressed date juice. A study found that the juice decreased the reproduction of Streptococcus causing febrile disease by 88.5%. Another study found that sap extracts dissolved in water and ethanol have a strong antibacterial activity against Escherichia coli, Salmonella enterica, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella abec and Enterococ. This germicidal effect is thought to be caused by tannic acid, gallic acid, itaconic acid and ferulic acids that are present in dates [5]. In another study, different degrees of influence were observed between different types of dates. It has been reported to be more efficient against Gram-negative bacteria due to the presence of an outer membrane in Gram-positive bacteria. This effect against microbes is due to phenolic compounds that enable the production of hydrogen peroxide, which stops the growth of bacteria.

Antitoxic activities

There are many studies about the protective effects of dates on the liver, kidney, and nervous system in neutralizing the oxidative stress and poisonous compounds that are obtained from food. It has been shown that p-Sitosterol, a bioactive compound often found in dates, is beneficial for liver injury when date seed powder is added to drinking water [6]. Another study showed the anti-damage effect of the succulent extract of dates on damaged liver cells related to oxidative stress [7].

Kidney-protective role

It is known that toxic substances that enter our body from the environment in various ways can cause great damage to us, especially to our kidneys. An extract prepared from date seeds has been shown to provide significant protection in the kidneys and remove harmful free radicals. This is thought to be due to the proanthocyanidin it contains. Another study showed improvements in mice with impaired renal function.

Scientists concluded that dates show significant improvements in the damage done to the kidneys by aflatoxin, a dangerous fungus that reproduces in foods, which can also be attributed to its antioxidant properties. Scientists believe that the effect here is due to the common effect of melatonin, vitamin E, and ascorbic acid in the extract [8].

Its influence against nerve poisoning

Free radicals have been extensively proven to cause aging and a multitude of age-associated diseases such as Alzheimer’s, Parkinson’s and dementia due to circulatory system failure [9]. Antioxidants obtained from plants have long been used to help prevent neurons from weakening and dying [10]. Studies are concentrated on the effectiveness of joint protection by polyphenolic compounds (resembling flavonoids and plant sterols) and the ascorbic acid that is found in date extract.

Its effect on the cardiovascular system

Dates have been used against high blood pressure for centuries. In one study, an enzyme in dates has been shown to suppress a specific blood pressure hormone called angiotensin [11]. High sodium and low potassium intakes increase blood pressure, whereas dates help maintain electrolyte balances and keep blood pressure in control. Magnesium and calcium in dates play a key role in this control [12]. It has been reported that cholesterol absorption and metabolism can be regulated by the suppression of cholesterol production in the liver due to the fermentation of phytoestrogens in dates [13].

In another study, a Pakistani date variety has been shown to be very effective in lowering compounds such as preprandial blood sugar, cholesterol, triacylglycerol, LDL, and VLDL. In another study, some chemical components such as P-sitosterol, proanthocyanidin, catechin, quercetin, anthocyanins, and selenium have been shown to both protect the heart and lower blood fats [14].

Each and every day, scientific studies are teaching us more about dates and how they have been equipped with more features than any other fruit as we strive to unveil the wisdom and mercy among the bounties offered to us in the shape of food.

References

1. Biglari, F., Al Karkhi A.F.M., Easa, A.M. (2008): Antioxidant activity and phenolic content of various date palm (Phoenix dactylifera) fruits from Iran. Food Chem 2008; 107(4): 1636-41.
2. Eid, N., Enani, S., Walton G., Corona G., Costabile, A., Gibson, G., Rowland, I., Spencer, J.P.E. (2014): The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation. J Nutr Sci 3: e46.
3. Hasan, M., Mohieldein, A. (2016): In Vivo Evaluation of anti-diabetic, hypolipidemic, antioxidative activities of saudi date seed extract on streptozotocin induced diabetic rats. J. Clin. Diagn Res. 10(3): FF06-12.
4. Al-Qarawi A.A., Abdel-Rahman H., Ali B.H., Mousa H.M., El-Mougy S.A. (2005): The ameliorative effect of dates (Phoenix dactylifera L.) on ethanol-induced gastric ulcer in rats. J Ethnopharmacol. 98(3): 313-7.
5. El Sohaimy S., Abdelwahab A., Brennan C., Aboul-enein A. (2015): Phenolic content, antioxidant and antimicrobial activities of Egyptian date palm (Phoenix dactylifera L.) fruits. Aust. J. Basic Appl. Sci. 9(1): 141-7.T
6. Al-Qarawi A.A., Mousa H.M., Ali B.H., Abdel-Rahman H., El-Mougy S.A.(2004): Protective effect of extracts from dates (Phoenix dactylifera L.) on carbon tetrachloride-induced hepatotoxicity in rats. Int. J. Appl. Res. Vet. Med. 2(3): 176-80.
7. Saafi E.B., Louedi M., Elfeki A., Zakhama A., Najjar M.F., Hammami M., Achour L. (2011): Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver. Exp. Toxicol. Pathol. 63(5): 433-41.
8. Al-Qarawi A.A., Abdel-Rahman H., Mousa H.M., Ali B.H., El-Mougy S.A.(2008): Nephroprotective Action of Phoenix dactylifera. in Gentamicin-Induced Nephrotoxicity. Pharm. Biol. 46(4): 22730.
9. Uttara, B.; Singh, A.; Zamboni, P.; Mahajan, R.(2009): Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr. Neuropharmacol. 7(1): 65-74.
10. Pujari R.R., Vyawahare N.S., Kagathara V.G. (2011): Evaluation of antioxidant and neuroprotective effect of date palm (Phoenix dactylifera L.) against bilateral common carotid artery occlusion in rats. Indian J. Exp. Biol. 49(8): 627-33.
11. Braga F.C., Serra C.P., Junior N.S.V., Oliveira A.B., Cortes S.F., Lombardi J.A.(2007): Angiotensin-converting enzyme inhibition by Brazilian plants. Fitoterapia 78(5): 353-8.
12. Tang Z-X, Shi L-E, Aleid S.M. (2013): Date fruit: chemical composition, nutritional and medicinal values, products. J. Sci. Food Agric. 93(10): 2351-61.
13. Alsaif M.A., Khan L.K., Alhamdan A.A.H., Alorf S.M., Harfi S.H., Al- Othman A.M., Arif Z.(2007): Effect of dates and gahwa (Arabian coffee) supplementation on lipids in hypercholesterolemic hamsters. Int. J. Pharmacol. 3(2): 123-9.
14. Auger C., Teissedre P.-L,. Gerain P., Lequeux N., Bornet A., Serisier S., Besancon P., Caporiccio B., Cristol J.-P., Rouanet J.-M.(2005): Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J. Agric. Food Chem. 53(6): 2015-21.

Despite that, there are more than 100 types of amino acids found in nature; only 20 of them are employed for protein synthesis. Among these 20 amino acids, excepting glycine, which does not display chirality, only the L-form of the 19 is used for protein synthesis. This is because ribosomes, where protein synthesis occurs, do not feature the utilization of D-form amino acids. As nothing in the universe exists in vain but with multiple tasks, D-amino acids have a job in the maintenance of life after protein synthesis in very different fashions. The way D-amino acids are employed in the execution and control of physiological preferences amazes scientists.

Up until recent times, D-amino acids were believed to be synthesized mostly by bacteria and plants, unlike mammals, and were considered dysfunctional as they passed, via consumption of nutrients, from bacteria and plants. However when D-amino acids were noticed for having roles as important as L-amino acids during the 1990s, the field gained significance. It was demonstrated that D-amino acids were found widely in invertebrates, vertebrates, and humans as free forms or inside proteins, undertaking critical functions in the nervous and endocrine systems. The most interesting point is the conversion of amino acids from the L-form into the D-form after the protein synthesis occurs in the peptides that are present in the venomous secretions of various animals. This conversion leads to the alteration of the peptide identity and function. Racemase and isomerase (epimerase) enzymes are utilized as they are created for this task. Usually, one or two amino acids of the D-form peptides are in D-form.

When chemist Gunther Kreil of the Austrian Academy of Sciences learned about the use of South American poisonous tree frogs (Phyllomedusa sauvagei ) during Shamanic hunting ceremonies by local Peruvian tribe (Matses), he studied this poison in detail. Participants of the ceremony first caused a burn on their chest region, then applied the poison they obtained from the frog skin over it. Diarrhea and tachycardia started within a minute, followed by a brief faintness. Once they recovered after a few minutes, they were to find themselves in a much more vigorous and exhilarated state of mind. The poison they were applying to their chest contained the dermorphin peptide, which has psychoactive, hallucinogenic effects and a D-amino acid. This peptide is a pain killer 30-40 times more effective than morphine. Among the 7 amino acids found in this peptide (heptapeptide), all are in L-form, except for one. Only the alanine, as the second in the peptide sequence, is in D-form and is produced via the isomerase enzyme from the L-alanine after the protein synthesis. G. Kreil discovered this D-form synthesizing enzyme in 2005. When this peptide was synthesized artificially in the laboratory, it did not display any biological activity or hallucinogenic effect. After a careful investigation of the case, it was found that frog skin based peptide had a D-form alanine second in its sequence; however, the one produced in laboratory had an L-form alanine. It was the presence of only one D-amino acid that made the difference in discovering the identity and function to the natural peptide in the poison.

In recent years dermorphin has started to be used as an illegal performance enhancer during horse races because of its pain killer feature. Horses on dermorphin can run longer and faster since they cannot feel the pain related to foot fatigue.

P. Kuchel of Sydney University also showed a D-amino acid presence in the peptide structured of the poison in the Platypus, a semiaquatic egg-laying mammal. Males use this poison as a weapon to fend off competitors. In 2009, Matthew Waldor and his friends at Harvard University discovered that the sugar-protein mix (matrix) called peptidoglycan found in the composition of bacterial cell walls is structured in a way to contain primarily D-alanine, D-methionine, and D-leucine. More interestingly, D-amino acids of the peptidoglycan structure were able to play a stimulatory role in coordinating the activities of other bacteria in the colony. For example, they acted as light houses in the use of florescence and helped in the formation of thin layers (bio-films) on various surfaces in bacteria. Once we understand the way D-amino acids help in communication between bacteria, it will be possible to use them as a drug. It’s possible they can be used to disintegrate bacteria that forms on teeth, in the lungs of cystic fibrosis patients, on clogs in fuel lines and water tanks, and in medical devices such as catheters.

D-amino acid containing peptides found in lobsters help maintain salinity levels and facilitate courtship in mating seasons. In recent years, D-amino acid containing antimicrobial peptides were discovered (bombinines) in the secretion glands of fire-bellied toad skins (Bombina sp). In this peptide, the second amino acid was in the D-form (D-allo-isoleucine). Two different peptides were found containing D-amino acids in the second position of the amino acid sequence of the poison secreted by Platypus males.

One of the reasons for D-amino acids to exist in animal poisons is that peptides containing D-Amino acids can not be easily degraded by the proteases (peptide bond breaking enzyme) of the host or opponents. Even though proteases can quickly and easily digest proteins composed of L-form amino acids, they struggle to do so with peptide bonds between D and L form amino acids. Pharmaceutical companies are trying to add D-amino acids to the peptide-structured drugs to prevent the quick degradation of peptides and proteins used for treatments when ingested. However, the addition of a D-form amino acid brings the high possibility of a situation that changes the function of a peptide or protein, or causes the loss of a protein. Nonetheless, specialists in this field point out that at least some amount of the D-amino acids that are produced by trillions of bacteria found on the skin, in the digestive track, and among other parts of the body can still be utilized for human health and convenience.

The D-serine of the mammalian nerve systems (glial cells and neurons), the D-aspartate of the neuro-endcorine, endocrine tissues, and testicles, and the D-alanine and D-aspartate amino acids of aquatic animals are abundant. D-Serine in the brain is synthesized by the conversion of L-serine into D-serine by the serine racemase enzyme. D-aspartate is in charge of hormone synthesis and secretion, and the regulation of spermatogenesis, and is produced by aspartate racemase and degraded by D-aspartate oxidase. It is also predicted to play role in the synthesis of hormones such as melatonin and testosterone.

As of now, four enzymes have been detected to be in charge of D-amino acid metabolism in mammals. How these are controlled is still unknown.

Publications pertaining to the association of epilepsy, schizophrenia, and bipolar disorders with enzymes in charge of D-amino acid synthesis and break down have increased in recent years. From this point of view, serine racemase and D-amino oxidase can be used to develop new potential drugs regarding the treatment of similar NMDA receptor associated diseases.

The first data demonstrating the use of D-amino acids in saliva in organs outside of the human brain was obtained by Y. Nagata and his team at the University of Nihon, Tokyo. A team led by Kenji Hamase of the Kyushu University discovered high levels of D-alanine storage in the beta cells of the rat pancreas. Kuchel, who discovered the enzymes converting the L-amino acids in to D forms in duck-billed Platypus poison, also found similar enzymes in the hearts of mice and humans. According to Kuchel, the physiological roles of those in humans remain to be unknown.

As a result, the common feature of toxins and antimicrobial peptides that are produced and secreted by animals is to contain D-amino acid. These peptides can be the source of a potential drug in the treatment of diseases such as cystic fibrosis, schizophrenia, and macular degeneration of the eye.

These prove that, especially in biology, exceptions are common; life is enriched via examples of extraordinary lives, processes, and mechanisms in unexpected places by unpredictable molecules or interesting reactions that can’t be predicted. Such discoveries help deepen our wonder at the intricacy and wisdom of creation.