Folic Acid Benefits For Men: Why You Should Eat Folate Rich Foods

Folate is one of the water soluble vitamins, vitamin B9, which your body cannot synthesize on its own; you must eat foods rich in folate if you don’t want to develop symptoms associated with its deficiency. Whereas folate is a natural product, folic acid is the synthetic form of it and has several benefits for men. It is an essential micronutrient required for the synthesis of both RNA and DNA, for cell division, growth and development.

When there is a deficiency of folic acid in your body, the cellular processes which require folate would be hampered. This may lead to several autoimmune and metabolic disorders.

 

Health Risks Associated With Folate Deficiency

Because folic acid plays vital roles in most cellular metabolism, it is therefore natural that its deficiency would forestall several health processes.

Some of the health implications of folic acid deficiency include cardiovascular diseases, memory loss, infertility, anemia, dizziness, depression and general weakness of the body. Folate deficiency has also been associated with carcinogenesis of several cancer cell lines.

 

 Folic Acid Benefits For Men

Folate is beneficial for men as well as for women. But because the folic acid benefits for men as well as for women are broad, we shall discuss each benefit in details.

 

 Folate reduces the risk of stroke

Cardiovascular disease is one of the risk factors for developing stroke, and sadly, it has grown in prevalence and continued to increase.

Cardiovascular diseases may be associated with coronary heart attacks and death.

Interestingly, folate seems to offer some ray of hope as some studies have shown that it reduces the risk of stroke in cardiovascular diseases patients.

These studies may also help non-cardiovascular disease patients in improving heart health and thus reduce the risk of cardiovascular diseases.

 

 Folate Enhances Man’s Fertility

The benefits of folate in men could be seen through the effect of its deficiency.

One of the major contributions of infertility among men include impaired spermatogenesis.

Folate deficiency can evidently reduce the gene expression levels of ESR1, CAV1 and ELAVL1, which are critical to spermatogenesis.

Another factor of infertility is low sperms counts or volume. Because folate regulates the expression of the gene responsible for production of sperms, it deficiency would hence affect the quality and volume of the sperm cells, and hence, reproduction.

Luckily, folate can be sourced from natural means like fruits and vegetables, and synthetic means like folic acid from pharmaceutical stores.

 

 Folic Acid Enhances Memory

Folic acid plays a role in the methylation of homocysteine providing the methyl group for the conversion of methionine to s-adenosyl methionine. An increase in homocysteine (Hcy) levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging.

Low folate intake increases plasma homocysteine, which damages the vascular endothelium and increases the risk of cardiovascular diseases.

Homocysteine is also neurotoxic and hyperhomocysteinemia has been associated prospectively with higher risk of Alzheimer’s disease.

Studies show that folate supplementation improves short- and long-term memory and motor coordination in adult male rats in a dose-dependent manner.

Read also (How zinc supplementation prevents Viral replication in covid-19 patients)

Read also (Benefits of Zinc in Sexual Functions)

 

 Folate Plays Major Roles In Central Nervous System

The importance of folate can also be seen in the central nervous system. It has fundamental roles in the functions of the central nervous system, and is an important factor for normal development and function of the CNS in all ages.

A study showed that the effect of folic acid supplementation is not restricted to the embryonic period but can also enhance growth, repair, and recovery in the injured CNS of adult rats. This study also supports claim of folic acid benefits in men.

 

Plays A Major Role In Bone Formation and Osteoporosis

Homocysteine has been pointed out as an independent risk factor for several health diseases such as liver, kidney and heart diseases. But it doesn’t stop at those diseases, as homocysteine has also been associated with osteoporosis.

A higher level of homocysteine concentration may lead to bone diseases, of which osteoporosis is one among them.

According studies, it is clearly evident that homocysteine directly activates osteoclast formation and activity, in vitro, via increased oxidative mechanism and mitochondrial MMP activation causing bone matrix degradation and alterations in the biomechanical properties of bone. Furthermore, it is evidenced that homocysteine decreases bone blood flow, as a consequence of decreased bioavailability of NO, affecting bone structure.

But with high level of folate in the plasma, homocysteine is reduced, thereby suppressing its adverse effects on the bone formation and bone resorption. Folate also suppresses homocysteinuria.

 

Folate And Vitamin E Enhance Fertility

Folic acid is not only beneficial to men; it is also beneficial to women’s fertility, as it prevents early pregnancy complications that might lead to miscarriages. Taking folic acid supplements can greatly increase your chances of becoming pregnant. Some studies suggest that a woman take folic acid supplements three months before scheduled time for conception.

Vitamin E plays a major role in the body as a strong antioxidant. It prevents free radicals from affecting the sperm DNA and spermatogenesis. Vitamin E improves sperm motility, thereby increasing rate of transport to and fertilization of the egg in fallopian tube. But that’s not all; vitamin E also improves sperm count, which is one of the risk factors affecting men’s fertility.

 

Folate Is Required For DNA Synthesis

The importance of Folate or folic acid is seen in the synthesis of RNA and DNA in gene transcription. Folate is used in the methylation of homocysteine to methionine, which is then used in the synthesis of s-adenosylmethionine (S-AdoMet), which is the universal methyl group donor for the methylation of RNA, cytosine bases in DNA, histones, and other small molecules.

 

Folate Deficiency May Result In Several Cancer Cell Growth

Folate deficiency can result in alterations in the nucleotide pool for DNA synthesis, leading to misincorporation of uracil into DNA, decondensed chromosomes, double stranded breaks, and translocations. Additionally, folate deficiency may reduce or alter DNA methylation, interfering with gene regulation and leading to carcinogenesis.

 

Do Not Take Folate Supplement If You have enlarged Prostate

Although folate plays great roles in cellular functions, it has a conflicting role in prostate cancer proliferation and invasion. Therefore, if you are taking treatment for prostate cancer, it is in your best interest to avoid folic acid supplementation.

 

Natural Sources of Folate

Although folic acid is synthetic and can be purchased off the pharmaceutical stores around you, there are several natural sources of folate for the metabolic and cellular functions of your body. Some of these natural sources shall be discussed briefly in this article.

 

Avocado Fruits and seeds

Avocado fruits are great sources of folate and vitamin E, making it a good source of folate and vitamin E. This also showed that regular consumption of avocado fruits and avocado seed tea will protect your body from the folate deficiency-associated diseases.

Also, consuming avocado fruits may improve your fertility level, since it is rich in both folate and vitamin E.

 

Black Sunflower Seeds

Another good source of folate and vitamin E is black sunflower seed. It is both nutritional, being packed with several vitamins and amino acids, including essential fatty acids. Black sunflower seeds improve your cholesterol levels by reducing total cholesterol, tr glycerides, and low density lipoproteins while increasing the plasma level of high density lipoproteins. It is also very good for improving heart health.

Other Sources of Folate may include

  • Banana
  • Egg
  • Meat
  • Groundnut and nuts
  • Fruits
  • Vegetables

 

Conclusion

Considering the health benefits of folic acid to men and women, it is proper that you start taking care of the foods you eat on daily basis, if they contain proper amount of folate or not. It may be the best option to buy folic acid from the pharmaceutical stores, at your doctor’s approval, and take them as food supplements.

The importance of folate and folic acid benefits to men cannot be overemphasized; neither can they be covered in one article. It is more hope, however, that you got values reading through.

However, for anyone with enlarged prostate gland, it would be a better idea to avoid folic acid supplementation, as doing so may increase the chances of developing prostate cancer proliferation and invasion.

 

References

Brocardo PS, Budni J, Kaster MP, Santos AR, Rodriques AL. Folic acid administration produces an antidepressant-like effect in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Neuropharmacology. 2008;54:464–473. [PubMed] [Google Scholar] [Ref list]

ca U. Low folate and the risk of cognitive and functional deficits in the very old: The monzino 80-plus study. J Am Coll Nutr .

Chen H, zhang SM, Schwarzschild MA, Hernan MA, Logroscino G, Willett WC, et al. Folate intake and risk of Parkinson’s disease. Am J Epidemiol. 2004;160:368–375.

Mattson MP, Kruman II, Duan W. Folic acid and homocysteine in age-related disease. Aging Res Rev. 2002;1:95–111. [PubMed] [Google Scholar] [Ref list]

Irani, M., Amirian, M., Sadeghi, R., Lez, J. L., & Latifnejad Roudsari, R. (2017). The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis. Urology Journal, 14(5), 4069-4078.

Iskandar BJ, Nelson A, Resnick D, Dkene JH, Gao P, Jnson C, et al. Folic acid supplementation enhances repair of the adult nervous system. Ann Neurol . 2004;56:221–227.

Reynold E. Vitamin B12 folic acid, and the nervous system. Lancet Neurol. 2006;5:949–960.

Yuan, H. F., Zhao, K., Zang, Y., Liu, C. Y., Hu, Z. Y., Wei, J. J., Zhou, T., Li, Y., & Zhang, H. P. (2017). Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis. Oncotarget, 8(15), 24130–24141. https://doi.org/10.18632/oncotarget.15731

Wang, Y., Jin, Y., Wang, Y., Li, L., Liao, Y., Zhang, Y., & Yu, D. (2019). The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis. Medicine, 98(37), e17095. https://doi.org/10.1097/MD.0000000000017095

Pravst, I., Lavriša, Ž., Hribar, M., Hristov, H., Kvarantan, N., Seljak, B. K., Gregorič, M., Blaznik, U., Gregorič, N., Zaletel, K., Oblak, A., Osredkar, J., Žmitek, K., & Kušar, A. (2021). Dietary Intake of Folate and Assessment of the Folate Deficiency Prevalence in Slovenia Using Serum Biomarkers. Nutrients13(11), 3860. https://doi.org/10.3390/nu13113860

Figueiredo, J. C., Grau, M. V., Haile, R. W., Sandler, R. S., Summers, R. W., Bresalier, R. S., Burke, C. A., McKeown-Eyssen, G. E., & Baron, J. A. (2009). Folic acid and risk of prostate cancer: results from a randomized clinical trial. Journal of the National Cancer Institute101(6), 432–435. https://doi.org/10.1093/jnci/djp019

Stover PJ, Field MS. Trafficking of intracellular folates. Adv Nutr. 2011; 2:325–31

Blount BC, Ames BN. Analysis of uracil in DNA by gas chromatography-mass spectrometry. Anal Biochem. 1994; 219:195–200.

Krumdiek C, Howard-Peebles P. On the nature of folic acid-sensitive fragile sites in human chromosome: an hypothesis. American Journal of Medical Genetics. 1983; 16:23–28.

P. van Wijngaarden, E. L. Doets, A. Szczecińska, O. W. Souverein, M. E. Duffy, C. Dullemeijer, A. E. J. M. Cavelaars, B. Pietruszka, P. van’t Veer, A. Brzozowska, R. A. M. Dhonukshe-Rutten, C. P. G. M. de Groot, “Vitamin B12, Folate, Homocysteine, and Bone Health in Adults and Elderly People: A Systematic Review with Meta-Analyses”, Journal of Nutrition and Metabolism, vol. 2013, Article ID 486186, 19 pages, 2013. https://doi.org/10.1155/2013/486186

 

 

 

Effect of Black Seed Thymoquinone on Rheumatoid Arthritis

Thymoquinone (2-isoprpyl-5-methyl-1,4-benzoquinone) is the most active component of Black cumin (Nigella sativa) seed oil. It is widely used in traditional medicine to treat a wide range of illnesses.

According to various research findings, thymoquinone exert important health-beneficial effects including antioxidant, anti-inflammatory and anti-cancer effects. As an antioxidant agent, thymoquinone normalizes glutathione levels and increases the activity of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase.

 

Black Cumin Tea Contains Thymoquinone

Black cumin seed is made into a tea and served as an antioxidant agent. Since it contains thymoquinone and other biologically active phytochemicals, black cumin seed tea should be recommended for patients who suffer rheumatoid arthritis. It can also be served to cancer patients who are undergoing chemotherapy.

How To Prepare Black Cumin Seed Tea

  • To prepare black cumin seed tea, assemble 2 cups of water, 2 tea spoonful of raw black cumin seeds and honey. Then follow the steps as follows:
  • Add the 2 cups of water and black cumin seeds in a pot and heat till it boils.
  • Remove from heat once it boiled.
  • Cover the pot and allow it to steep for about 10 minutes.
  • Strain the water into a cup using a mesh. You may add the seed to enjoy the whole benefits if you so wish.
  • Add two spoonful of honey and stir
  • Serve and enjoy your tea

 

Benefits of Thymoquinone and Black Cumin Seed Tea in Treatment of Rheumatoid Arthritis

The uncontrolled inflammation associated with rheumatoid arthritis arises as a result of the uncontrolled production and activity of various inflammatory cytokines, TNFα, IL-1, IL-17, IL-6 and the resulting inflammation is responsible for the pain, tenderness, swelling, redness and stiffness of joints.

Black cumin seeds and especially thymoquinone has been shown to be beneficial against rheumatoid arthritis and autoimmune diseases.

 

Thymoquinone Inhibits NF-kB Signaling In Rheumatoid Arthritis

NF-kB regulates the expression of many genes, enzymes, cytokines, cell cycle regulatory molecules as well as angiogenic factors. It induces inflammation by influencing the expression several pro-inflammatory cytokines, chemokines , acute phase proteins and growth factors.

Thymoquinone inhibits NF-kB induced inflammatory response in rheumatoid arthritis patients by inhibiting its translocation into the nucleus. Thymoquinone also inhibits NF-kB activities by suppressing TNF-induced-NF-kB activation. This is done by inhibiting TNF-induced IKBα phosphorylation and degradation as well as p65 phosphorylation and nuclear translocation.

 

Thymoquinone Inhibits Prostaglandins and COX-2 in Rheumatoid Arthritis

Prostaglandins (PGs) are arachidonic acid metabolites. They are found at elevated levels in synovial fluid and also in synovial membrane, where they function in the development of vasodilation, fluid extravasation and pain in synovial tissues. Aside these functions, Prostaglandin E2 (PGE2) and COX are upregulated in synovial tissues in rheumatoid arthritis patients, where PGE2 synergizes with IL-23 to stimulate Th17 cell proliferation.

Th17 in turn stimulates the release of pro-inflammatory cytokines and promotes bone resorption. PGE2 also mediates complex interactions that lead to the development of articular cartilage erosions and juxta-articular bone.

Cyclooxygenase enzymes (COX), especially COX-2 are involved in inflammatory responses. COX-2 is induced by pro-inflammatory cytokines, mainly IL-1.

Thymoquinone suppresses the expression of COX-2 protein by inhibiting NF-kB signaling pathway activation and induces the expression of cytoprotective enzymes.

Effect of Thymoquinone on PI3k/Akt Signaling Pathway

Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway is an intracellular regulatory signal transduction pathway that is activated by toxic substances or cellular stimuli that regulate many cellular processes including cell growth, survival and apoptosis.

When abnormally activated, PI3K/Akt signaling pathway is involved in the pathogenesis of many diseases including diabetes mellitus, cancer, and rheumatoid arthritis. In RA, PI3K/Akt signaling pathway play important role through the expression of different types of pro-inflammatory mediators that degrade IKβ and activate NF-kB signaling pathway.

Thymoquinone induces apoptosis by blocking PI3K/Akt signaling pathway in DU-145 cell line. It also deactivate PI3K/Akt and NF-kB signaling pathway and regulate various gene products such as p65 and COX-2.

 

REFERENCES

J.K. Kundu, L. Liu, J.-W. Shin, Y.-J. Surh., Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo Biochem. Biophys. Res. Commun., 438 (4) (2013), pp. 721-727

 

Umar, J. Zargan, K. Umar, S. Ahmad, C.K. Katiyar, H.A. Khan Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats Chem. Biol. Interact., 197 (1) (2012), pp. 40-46

 

Vaillancourt, P. Silva, Q. Shi, H. Fahmi, J.C. Fernandes, M. Benderdour

Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis J. Cell. Biochem., 112 (1) (2011), pp. 107-117

 

Thymoquinone inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by suppressing NF-κB and MAPKs signaling pathway Inflammation, 38 (6) (2015), pp. 2235-2241

 

Khan, A. Sureda, T. Belwal, S. Çetinkaya, İ. Süntar, S. Tejada, H.P. Devkota, H. Ullah, M. Aschner. Polyphenols in the treatment of autoimmune diseases. Autoimmun. Rev., 18 (7) (2019), pp. 647-657

 

Stańczyk J, Kowalski ML. Rola cyklooksygenaz oraz prostaglandyn w patogenezie reumatoidalnego zapalenia stawów [The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis]. Pol Merkur Lekarski. 2001 Nov;11(65):438-43.

 

Benefits of Zinc in Sexual Functions

What is Zinc?

Zinc, though beneficial for men’s sexual health, is a chemical element with an atomic number 30 and represented by the symbol, Zn. It is slightly brittle at room temperature and has a silvery-grayish appearance when oxidation is removed.

In the periodic table, zinc is the first element in the 12th group and in the 4th period. It possesses similar characteristic with magnesium; both elements exhibit one normal oxidation state, only (+2) and are similar in size.

It should be noted that Zinc is the 24th most abundant element in Earth’s crust and has five stable isotopes. The common Zinc ore being Sphalerite, a zinc sulfide mineral. Despite being the 24th most abundant element, Zinc is still a trace element in our body. meaning that our body require only a small amount of it in our circulatory systems.

What Are The Sources Of Zinc?

Zinc can be sourced from several foods such as meats, fishes, fruits, seeds, vegetables, nuts and some times, from the leaves and roots of certain herbal plants. Some of the plant sources of Zinc includes:

Meats and Fishes

meats are excellent sources of zinc. But red meat are in particular, great sources of Zinc. An ample amount of zinc can be found, however, several other kinds of meat and fishes, most especially from sea foods.

Legumes

Legumes like groundnut, cowpea, pigeon pea, beans, and several others, are great source of zinc. When you eats meat, fish or legumes, you are sue going to enrich your body with increased amount of zinc.

Eggs

Eggs are another great source of zinc, Though they contain moderate amount of zinc, they sure would help you meet your daily zinc requirements. When you consume one egg, you are supplied with 5% f your daily dietary value of zinc.

Fruits and Seeds

Most plant fruits and seed such as Avocado peer, black sunflower seeds, apple, star apple, garden eggs and several others possess ample amount of zinc which your body would need to maintain daily functions. when you think of the added antioxidants in fruits and seeds, and consider the benefits they and zinc offer sexually, you would want to eat fruits every passing day for a good health and reproductive functions.

What  Are The Benefits Of Zinc, Sexually?

According to studies, male infertility is responsible for approximately 30-55% of infertility cases. The commonest cause of male infertility is sperm dysfunction. And this may be due to some risk factors like

  • Varicocele
  • Obstructive lesions
  • Cryptorchidism
  • Cystic fibrosis
  • Trauma
  • Genitourinary infections
  • Environmental factors and
  • Nutritional deficiency of trace elements, especially zinc, selenium, and vitamins.

During ejaculation, the sexual accessory glands secrete serminal plasma which contains some elements that protect spermatozoa. Some of the serminal contents include,

  • Acid phosphatase
  • Alanine transaminase
  • Alkaline phosphatase
  • Aspartate transaminase
  • Lipids and

Zinc plays important role in male fertility by enhancing germinal cell proliferation, cell division, immune system and gene expression. And a dietary zinc deficiency is a risk factor low quality of sperm and idiopathic male infertility.

Zinc Enhances Testosterone Production

Low sperm zinc levels have a negative effect on serum testosterone concentration. It also affects the normal function of the hypothalamus-pituitary-gonadal axis. Zinc helps the body maintain proper thyroid function by producing hormones called thyroid-releasing hormones in the brain.

Thyroid hormones have several important roles in the body including metabolism, development and even body temperature. Whenever men are low in Zn, they
may fail to produce enough of these hormones. That can also affect testosterone levels.

According to a clinical study, adult males who denied themselves Zinc supplementation showed a disorder of testosterone synthesis in the Leydig cell. This is because zinc has a main role in the 5α reductase enzyme that is necessary for the transformation of testosterone into biologically active form, 5α dihydro testosterone.

How Does Zinc Enhances Testosterone production?

Zinc boosts male fertility via enhancing testosterone production by modulating the balance between testosterone and 5α dihydro testosterone (DHT). This is done by regulating the activity of 5α-reductase, which converts testosterone to DHT. It is important for the Leydig cells and play important role in the physiology of spermatozoa.

Benefits of Zinc Sexually in Sperm Count and Motility

During initiation of spermatogenesis, zinc participates in the ribonuclease activity as well as involves in spermatozoa maturation, maintains germinal epithelium and seminiferous tubule. It also enhances sperm motility and concentration during ejaculation.

Several studies have demonstrated that oral Zinc supplementation improves sperm motility in subfertile men with idiopathic asthenozoospermia and/oroligozoospermia. The negative correlation between seminal plasma Zn and sperm viability is a good sign of the importance of Zn in spermatogenesis.

Zn therapy improves sperm quality with increases in sperm density, progressive motility and improved conception and pregnancy outcome. Zn plays an important role in membrane-stabilizing and antioxidant activity and maintains sperm viability by inhibiting DNases.

Zinc Antibacterial Activities Enhances Sperm Health

One of the risk factors of sperm dysfunction is genitourinary infection. The antibacterial activity of zinc improves sperm health and sperm count by clearing bacterial infections. The oxide of zinc, ZnO has antimicrobial activities against both gram negative and gram positive bacteria as well as against spores. But the mechanism of action of ZnO against antimicrobial activity is yet to be elucidated.

Zinc Is Beneficial For Men’s Prostate Function

Apart from the Being Beneficial men’s sexual health, zinc also helps the prostate. It has been found that zinc inhibits the growth and invasion of prostate cancer cells. One of the ways zinc suppresses prostate cancer growth is through the suppressing the activity of mitochondrial aconitase and inhibition of the terminal oxidation in the electron transport chain. But that’s not all there is about Zinc; it also imposes apoptogenic effect and suppresses progression while protecting DNA integrity in the prostate cell.

 

REFERENCES

Aditya, A., Chattopadhyay, S., Jha, D., Gautam, H. K., Maiti, S., and Ganguli, M. (2018). Zinc oxide nanoparticles dispersed in ionic liquids show high antimicrobial efficacy to skin-specific bacteria. ACS Appl. Mater. Interfaces 10, 15401–15411. doi: 10.1021/acsami.8b01463.

Ali H, Ahmed M, Baig M, Ali M. Relationship of zinc concentrations in blood and seminal plasma with various semen parameters in infertile subjects. Pak J Med Sci. 2007;23(1):111-4.

Akinloye O, Abbiyesuku FM, Oguntibeju OO, Arowojolu AO, Truter EJ. The impact of blood and seminal plasma zinc and copper concentrations on spermogram and hormonal changes in infertile Nigerian men. Reprod Biol. 2011;11(2):83-98.

Brown, A. N., Smith, K., Samuels, T. A., Lu, J., Obare, S. O., and Scott, M. E. (2012). Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureusAppl. Environ. Microbiol. 78, 2768–2774. doi: 10.1128/AEM.06513-11

Henkel R, Bittner J, Weber R, Hüther F, Miska W. Relevance of zinc in human sperm flagella and its relation to motility. Fertil Steril. 1999;71(6):1138-43.

Ho, E., & Song, Y. (2009). Zinc and prostatic cancer. Current opinion in clinical nutrition and metabolic care12(6), 640–645. https://doi.org/10.1097/MCO.0b013e32833106ee

Hunt CD, Johnson PE, Herbel J, Mullen LK. Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men. Am J Clin Nutr. 1992;56(1):148-57.

Khosronezhad N, Hosseinzadeh Colagar A, Mortazavi SM. The Nsun7 (A11337)-deletion mutation, causes reduction of its protein rate and associated with sperm motility defect in infertile men. J Assist Reprod Genet. 2015;32(5):807–15.

Omu A, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA, Mathew TC. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract. 2008;17(2):108-16.

Yuyan L, Junqing W, Wei Y, Weijin Z, Ersheng G. Are serum zinc and copper levels related to semen quality? Fertil Steril. 2008;89(4):1008–11.

Khan MS, Zaman S, Sajjad M, Shoaib M, Gilani G. Assessment of the level of trace element zinc in seminal plasma of males and evaluation of its role in male infertility. Int J Appl Basic Med Res. 2011;1 (2):93–6.

The Functions of Zinc in Immune System

Zinc is an essential macronutrient, which play a crucial role in multiple cellular functions, including immune cell signaling. In zinc dyshomeostasis, which includes zinc deficiency, there are impairments in several cellular and organ function including overall immune function and increased susceptibility to infection. This shows that zinc cannot be overlooked in immune system and other cellular processes.

Some of the problems associated with zinc deficiency are growth retardation, neurological disorder, immune dysfunction and Acrodermatitis enteropathica, a metabolic disorder.

 

Zinc Transporters

Zinc coordinates its signaling through two families of zinc transporters and metallothiones. The two families of zinc transporters are:

The Solute-linked carrier 39 (SLC39A or ZIP) family of zinc transporters, which transport zinc into the cytosol and out of the intracellular organelles and,

The Solute-liked carrier 30 (SLC30A or ZnT) family of zinc transporters, which transport zinc out of the cytosol and into the intracellular organelles.

Both ZIP and ZnT transporters are expressed in a cell- or tissue-specific manner.

Metallothione (MT)

Metallothione is a zinc-binding protein that functions as a reservoir of intracellular zinc. It has the ability to bind up to seven zinc ions per MT molecule. It also plays a crucial role in the distribution, transport and maintenance of intracellular zinc ions.

The Function of Zinc in Pathogen Invasion

Zinc regulates complex signaling pathways in immune cells. As a result, when an invasion by a pathogen occurs, the pathogen creates a conflict in which Zn becomes a shared resource.

In this battle-like state, the pathogen strives to utilize Zn for its biological functions at the expense o the host, while the host cells seek to reserve Zn and render it inaccessible for pathogen uptake. This strategy of the host cell curtails the growth of some pathogens, but there are some pathogen which resist this cellular mechanism by possessing strong Zn acquisition machineries that effectively compete with the host for Zn.

Excess zinc however, can exert toxic effects on microbial survival. And the immune cells have taken advantage of this to localize and fuel excessive Zn concentrations that intoxicate the pathogen without impacting host cells.

 

Zinc Signals in Monocytes and Macrophages.

The immune system provides two layers of defense against pathogens; they are innate and adaptive immunity. Innate immunity, which is the frontier of host defense, involves the recognition of pathogen-associated molecular patterns (PAMPs), conserved structures of invading pathogens, and the immediate initiation of immune responses.

During invasion, mononuclear phagocytes of innate immunity immediately recognize invading pathogens through the sensing of PAMPs by pathogen-recognition receptors (PRR), including Toll-like receptors (TLRs). Upon PAMP engagement, individual TLRs differentially recruit adaptor molecules such as MyD88, TRIF, TIRAP-dependent NF-kB, MARK, PI3K, and the TRIF/TRAM-dependent IRF3 pathway, and elicits a variety of monocyte and macrophage effectors’ functions.

 

TRIF/TRAM-dependent pathway

Signaling through TRIF activates several transcription factors, including NF-kB, IRF3, and AP-1. This leads to the production of cytokines and type-1 IFN, as well as maturation of myeloid dendric cells. Biological responses from TRIF-dependent signaling depends on both the type of cell responding and the particular TLR that is activated.

In TLR4 signaling, the TLR4 TIR domain use TRAM to recruit TRIF to the signaling complex, either by operating from the plasma membrane or from the endosomes. Localization of TRAM to the endosomes is necessary for IRF3 activation in the TRIF-dependent pathway.

When a lipopolysaccharide binds to TLR4, it leads to rapid zinc influx into the cytoplasm of monocytes and macrophages, which triggers zinc-mediated regulation of major signaling pathways, including TRIF/TRAM pathway.

 

MyD88/TIRAP-dependent NF-kB pathway.

The NF-kB transcription factor is a central regulator of proinflammatory gene induction and functions in a variety of immune responses. It influences the expression of proinflammatory cytokines, Chemokines, acute phase proteins, matrix metalloproteinase, adhesion molecules, growth factors, and other factors involved in inflammatory responses.

Zinc regulates the NF-kB activity by suppressing LPS-induced activation of IKKB. This is through a mechanism that is initiated by the inhibition of cyclic nucleotide phosphodiesterase (PDE), and subsequent elevation of cGMP, cross-activation of protein kinase A (PKA), and inhibitory phosphorylation of protein kinase Raf-1.

Another mechanism which involves direct inhibition of IKK upstream of NF-kB is mediated by ZIP8, which increase intracellular zinc, and involves a direct binding of Zn to IKKB.

 

 

Zinc (Zn)

Zinc (Zn) is a chemical element, which is an essential macronutrient for basic cell activities such as cell growth, cell differentiation and survival. It is found in high concentration in the red blood cells as an essential part of the enzyme, carbonic anhydrase, which promotes many reactions relating to carbon dioxide metabolism. In the pancreas, Zn aid in the production, secretion and storage of insulin.

The cellular functions of zinc can be found in the regulation, activation and expression of biological molecules such as transcription factors, enzymes, adapters, channels and growth factors, along with their receptors. When Zn is deficient or excessively absorbed, it disrupts Zn homeostasis and growth, morphogenesis and immune response, as well as neurosensory and endocrine functions.

Biological functions of Zinc

  • Zinc is required for the functions of many proteins, including enzymes and transcription factors.
  • It acts as a neuromodulator in synaptic transmissions.
  • Zinc behaves as a signal transducer to regulate cellular functions in which Zn transporters are involved.
  • Zinc is pivotal for mammalian oogenesis.
  • In plants and rats, Zn is essential for growth and development.
  • Zinc influences insulin production and secretion, and thereby influences blood glucose transport into cells and reduces hyperglycemia.
  • In diabetic patients, Zn supplementation lowers oxidative stress.

 

Zinc transporters

Zinc transporters are transmembrane proteins that control the movement of zinc across cellular membrane, distribution and storage. They belong to two major gene families, namely, The ZnT proteins (Solute-linked carrier 30, SLC30) and the ZIP ( Zrt/Irt-linked solute-linked carrier 39, SLC39).

ZIP Proteins

The ZIP proteins transport Zn into the cell through the plasma membrane or out of the subcellular organelles when cytosolic zinc is low or depleted. In mammals, there are fourteen members o the ZIP family. They have eight predicted transmembrane domains (TMDs) with an extracytosolic N- and C- terminals. Between TMD3 and TMD4, a long histidine-rich loop region is located.

ZIP family is expressed in a wide range of tissues and cells, and their proteins are located at distinct cellular compartments.

ZnT Proteins

Unlike ZIP, ZnT proteins transport Zn out of the cell through the plasma membrane or into the subcellular organelles when Zn cytosolic concentrations are high. They have a topology of six predicted transmembrane domains and a histidine-rich loop region between TMD4 and TMD5 with their N- and C- terminals located on the cytosolic side of the membrane. They are also expressed in a wide range of tissues and cells, and have distinct subcellular locations.

 

Zinc, Zn transporters, and Cell signaling

The process of cell signaling is complex and the role of Zn and Zinc transporters in cellular signaling is less defined.

Zinc mimics the actions of hormones, growth factors, and cytokines. It is actually taking precedence as a leading cell signaling molecule analogous to Calcium.

Modes of Zinc (Zn) signaling

There are two modes of Zn signaling, which are “early zinc signaling” (EZS) and “later Zinc signaling” (LZS).

Early Zinc Signaling: EZS involves a rapid change in intracellular levels of free Zn that occurs in minutes due to an extracellular stimulus that is transcription dependent. This rapid change in the intracellular free Zn is called “Zinc wave” and is dependent on both Calcium and MEK signaling.

Late Zinc Signaling: LZS is also triggered by an extracellular signal and involves transcription-dependent changes in expression of proteins involved in Zn homeostasis, such as storage proteins or transporters.

 

Role of Zinc (Zn) in Insulin Regulation

Zinc plays an integral role in the processing, storage and secretion of insulin by the pancreas, which subsequently increases glucose absorption. Whenever the plasma level of Zinc becomes low, it adversely affects the ability of the beta islet cells to produce and secrete insulin. By increasing the secretion of insulin, Zn promotes the phosphorylation of Akt (Also known as protein kinase B) and Glycogen synthase kinase 3B (GSK3B), which increase glucose uptake and reduces hyperglycemia.

Zinc deficiency and malabsorption has been linked to diabetes mellitus. This shows that Zn enhances insulin secretion and glucose uptake, thereby decreasing hyperglycemia, cellular apoptosis and excess glucose in kidney.

 

Zinc (Zn) Supplementation in Decreases Oxidative Stress

Hyperglycemia increases oxidative stress in diabetes mellitus. By decreasing blood glucose level, Zn reduces oxidative stress and protects the cells from oxidative injury. When combined with Chromium, Zn decreases thiobarbituric acid reactive substances’ (TBARS) levels. Zinc supplementation also increases glutathione levels, whereas lipid peroxidation is decreased.

 

 

Amino Acids

Amino acids are the building blocks of proteins. They are essential for the running and maintenance of normal body systems. Proteins are polymers of amino acids, with each amino acid residue joined to its neighbor by a specific type of covalent bond.

General Properties of Amino Acids

Each of the amino acids used in protein synthesis has the same structure. They contain a carboxylate acid group, an amino group attached to the Alpha-carbon in an L-configuration, a hydrogen atom and a chemical group called the side chain. The side chain is different in each amino acid compound.

In a solution and at physiological pH, the free amino acids exist as Zwitterions: that is ions in which the amino group is positively charged and the carboxylate group is negatively charged.

Classification of Amino Acids

Amino acids are classified based on the properties of their side chains. The side chains determine the types of bonds and interactions each biomolecule in a polypeptide chain can make with other molecules. Thus, amino acids can be grouped into five main classes based on the properties of their R-group, where R-group means the side chains.

  • Nonpolar, Aliphatic R-Group

    In this group, the R-groups are nonpolar and hydrophobic. Examples of amino acids in this group are Alanine, Valine, Leucine, and Isoleucine. They cluster together within proteins, stabilizing protein structure by means of hydrophobic interactions. Glycine is the smallest member of this group with its R-group being a hydrogen atom.

  • Nonpolar Aromatic R-Group

    Members of this group are hydrophobic. Phenylalanine, Tyrosine, and Tryptophan are members of this group. The hydroxyl group of tyrosine can form hydrogen bonds, which makes it an important functional group in some enzymes. Tryptophan and phenylalanine absorb ultraviolet light. This accounts for the strong absorbance of light by most proteins at a wavelength of 280nm, and this properties are exploited by scientists in protein characterization.

  • Polar, Uncharged R-Group

    The R-group of members of this family are hydrophilic, because they contain functional group that form hydrogen bonds with water. Members of this group include Serine, threonine, Cysteine, Asparagine and Glutamine.

  • Positively Charged (Basic) R-Group

    Members of this group include Lysine, Arginine, and Histidine. At the physiologic pH, the R-group of Lysine and Arginine are fully ionized and positively charged. Histidine is however weakly basic and the free amino acid is largely uncharged at physiologic pH. When Histidine is incorporated into a protein, its R-group can be either positively charged or neutral, depending on the ionic environment provided by the protein.

  • Negatively charged (Acidic) R-Group

    At physiologic pH, members of this group are fully ionized, containing a negatively charged carboxylate group (-Coo). Aspartic and Glutamic acids are the two members of this group, and therefore, are called Aspartate and Glutamate respectively, to emphasize that the members of this are negatively charged at physiologic pH.

 

Optical Properties of Amino Acids

The α-carbon of Amino acids is said to be a chiral or optically active carbon atom. This is because the α-carbon atom is attached to four different chemical groups. An exception however, is glycine, which is attached to two hydrogen atoms.

Amino acid with an asymmetric center at the α-carbon can exist in two forms, which are designated D and L, and are mirror images of each other. The two forms in each pair are called stereoisomers, optical isomers, or enantiomers.

Amino acids found in proteins are of L configuration. D-amino acids are however found in some antibiotics and in bacteria cell walls.

Inborn errors of metabolism

Inborn errors of metabolism are caused by specific changes in certain enzymatic reactions, in which the synthesis of certain amino acids are hampered by the changes in the enzyme’s structural-functional activity. Inborn errors in metabolism attack about 1 in every 5000 newborns. Some examples of inborn errors of metabolism include Alkaptonuria, Phenylketonuria, maple syrup urinary disease, etc.

Importance of Amino acids

  • Gamma amino butyric acid (GABA) is a derivative of glutamic acid and dopamine. It is a neurotransmitter. Gabapentin, which is an analog of GABA can pass through blood brain barrier and form GABA in brain. It is clinically used to relieve pain.
  • Histidine is the mediator of allergic reactions.
  • Thyroxine is an important thyroid hormone

Amino Acid Biosynthesis

The biosynthesis of each Amino acid is carried out in a unique pathway from that of another. This is because each of the amino acid, especially the 20 common amino acids, has a distinct structure. However, some generalities do apply to both the synthesis and the degradation of all amino acids.

Essential and nonessential amino acids

The 20 amino acids found in human body can be classified into essential and nonessential amino acids.

Essential amino acids are those that must be present in a diet, and which the body cannot synthesize. They include:

  • Arginine
  • Histidine
  • Isoleaucine
  • Leucine
  • Lycine
  • Methionine
  • Threonine
  • Phenylalaine
  • Tryptophan
  • Valine

The pathway for the synthesis of essential amino acids are found in plants and in bacteria, but not in animals.

Nonessential amino acids need not be present in the diet. They are basically synthesized by the human body. These amino acids are

  • Alanine
  • Asparagine
  • Aspartate
  • Cysteine
  • Glutamate
  • Glutamine
  • Glycine
  • Hydroxyproline
  • Hydroxylysine
  • Proline
  • Serine
  • Tyrosine

Important coenzymes in amino acids synthesis

Pyridoxal phosphate  Pyridoxal phosphate is derived from vitamin B6. It is involved in the removal of amino groups through transamination reactions and in donation of amino groups for various amino acid biosynthetic pathways. It is also required for certain reactions that involve the carbon skeleton.

Tetrahydrofolate (FH4) is a coenzyme that is involved in the transfer of one-carbon group at various oxidation states. FH4 is used in both amino acid degradation (e.g. Serine and Histidine) and biosynthesis (e.g. Glycine).

Tetrahydrobiopterin (BH4) BH4is a cofactor that is required or ring hydroxylation reactions (e.g. Phenylalanine to Tyrosine)

Biosynthesis of Amino Acids

 

Glutamate The amino acid biosynthesis of glutamate catalyzed by the transfer of an amino group to the α-ketoglutarate by glutamate dehydrogenase, a mitochondrial enzyme, in what is termed reductive amination reaction. The reaction strongly favors glutamate formation, which lowers the concentration of cytotoxic ammonium ion.

Alanine and Aspartate Transamination of pyruvate forms alanine while transamination of oxaloacetate forms aspartate. The amino donor may be glutamate or aspartate, and the reaction is catalyzed by the enzyme, aminotransferase.

Asparagine The conversion of aspartate to asparagine is catalyzed by asparagine synthase. It resembles the glutamine synthase reaction; however, glutamine rather than ammonium ion provides the nitrogen. In bacteria, asparagine synthase can also use ammonium ion.

Serine synthesis involves the oxidation of the α-hydroxyl group of 3-phosphoglycerate. The reaction is catalyzed by 3-phosphoglycerate dehydrogenase, which converts 3-phosphoglycerate to 3-phosphohydroxypyruvate. Transamination and subsequent dephosphorylation then forms serine. The hydrolytic removal of the phosphoryl group is catalyzed by phosphoserine hydrolase.

Glycine aminotransferases can catalyze the synthesis of glycine from glyoxylate and glutamate or alanine. Other important routes for glycine formation are from choline and from serine.

Proline The initial reaction converts ϒ-carboxyl group of glutamate to the mixed acid anhydride of glutamate ϒ-phosphate, which is subsequently reduced to glutamate ϒ-semialdehyde, and after cyclization reaction, it is reduced to L-proline.

Cysteine is formed by conversion of methionine to homocysteine. Homocysteine and serine form cystathionine, whose hydrolysis forms cysteine and homoserine. Cystathionine formation is catalyzed by cystathionine β-synthase.

Tyrosine The conversion of phenylalanine to tyrosine involves two distinct enzymatic activities. In the first activity, O2 is reduced to H2O and phenylalanine to tyrosine while in the second activity, dihydrobiopterin is reduced by NADPH.

 

What is the Mechanism of Action of Corticosteroid?

 

Corticosteroid is synthetic drug that mimic the adrenal hormone, cortisol, used in the management of many inflammatory and autoimmune health conditions. They modify the functions of epidermal and dermal cells and of leukocytes involved in proliferative and inflammatory diseases of the skin.

Corticosteroids can be used in treating several health conditions, such as:

  • Asthma
  • Allergies
  • Eczema
  • Hives
  • Psoriasis
  • Chronic obstructive pulmonary disease
  • Gout
  • Lupus
  • Multiple sclerosis
  • Autoimmune diseases

Types of corticosteroids

Corticosteroids come in different forms. Some of the corticosteroids used in treating inflammations include cortisone, prednisone and methylprednisolone. Prednisone is the most commonly used type of steroids used in treating certain rheumatoid diseases like rheumatoid arthritis or lupus.

 

How to administer corticosteroid

Corticosteroid comes in different forms based on their ease of administration. They can be localized of systemic.

Localized steroids target a specific part of the body and can be applied through:

  • Eye drops
  • Ear drops
  • Skin cream and ointments
  • Inhalers

Systemic steroids circulate through the blood. They can be applied by oral, intravenous or subcutaneous injection.

 

Mechanism of action of Corticosteroids

In its mechanism of action, corticosteroid react with receptor proteins in the cytoplasm to form a steroid-receptor complex. The complex thus formed moves into the nucleus, where it binds to DNA. By binding to the DNA and changing the transcription of mRNA, corticosteroid stimulates the production of glycoprotein called Lipocortin. Lipocortin inhibits the activity of phospholipase A2, which releases arachidonic acid, the precusor of prostanoid and leukoctrienes, from phospholipids. Corticosteroid also inhibits the transcription of mRNA responsible for interleukine-1 formation. Thus, by inhibiting arachidonic acid metabolism and interleukin-1 formation, steroids produce anti-inflammatory, immunosuppressive and anti-mytogenic effects.

Adverse effects of corticosteroids

Corticosteroid in its mechanism of action, especially glucocorticosteroid, has been shown to stimulate osteoclastic activity in the first 6-12 months of therapy, followed by a decrease in bone formation and life span. It promotes the apoptosis of osteolasts and osteocytes. It can also cause adrenal suppression in patients that are been treated with it.  Other side effects of steroids include cushingoid appearance and weight gain, hyperglycemia and diabetes, cataracts and glaucoma.

 

Antabuse may help revive vision in progressive blinding disorder

Antabuse (Disulfiram) is an inhibitor of aldehyde dehydrogenase, which is directly relevant to its role in curbing alcohol consumption. It is previously used in treating patients addicted to alcohol and/or cocaine consumption. Antabuse undermines dopamine transmission and dampen the euphoric and stimulant effect of cocaine.

 

Researchers at the University of California, Berkeley, have however discovered that Antabuse helps to improve sight in mice with retinal degeneration.

The drug may revive sight in humans with the inherited disease retinitis pigmentosa (RP), and perhaps in other vision disorders, including age-related macular degeneration.

A group of scientists led by Richard Kramer, UC Berkeley professor of molecular and cell biology, had previously shown that retinoic acid is produced when light-sensing cells in the retina, called rods and cones, gradually die off. This chemical causes hyperactivity in retinal ganglion cells, which ordinarily send visual information to the brain. The hyperactivity interferes with their encoding and transfer of information, obscuring vision.

However, he realised that Antabuse inhibits not only enzymes involved in the body’s ability to degrade alcohol, but also enzymes that make retinoic acid. In new experiments, Kramer and collaborator Michael Goard, who directs a lab at UC Santa Barbara (UCSB), discovered that treatment with disulfiram decreased the production of retinoic acid and made nearly-blind mice much better at detecting images displayed on a computer screen.

In 2019, Kramer and his team laid out the mechanism behind hyperactivity caused by degeneration. They found that retinoic acid, which is well-known as a signal for growth and development in embryos, floods the retina when photoreceptors — the rods, sensitive to dim light, and the cones, needed for color vision — die. That’s because photoreceptors are packed with light-sensitive proteins called rhodopsin, which contain retinaldehyde. When the retinaldehyde can no longer be absorbed by rods and cones, it is converted to retinoic acid by an enzyme called retinaldehyde dehydrogenase.

The retinoic acid, in turn, stimulates the retinal ganglion cells by adhering to retinoic acid receptors. It’s these receptors that make ganglion cells hyperactive, creating a constant buzz of activity that submerges the visual scene and prevents the brain from picking out the signal from noise. Drug developers may seek to prevent this by developing chemicals that would stop the production of retinoic acid by retinaldehyde dehydrogenase, or chemicals that interfere with the retinoic acid receptor.

The researchers are planning to partner with ophthalmologists to conduct a clinical trial of disulfiram on patients with RP. The trial would be carried out on a small set of people with advanced, but not yet complete, retinal degeneration.