The Mederi Blog

Why Zinc Is So Important (And Why You Might Be Deficient)

Originally posted at http://www.donnieyance.com/why-zinc-is-so-important-and-why-you-might-be-deficient/

I believe zinc deficiency might be the number one overlooked health concern facing our aging population. Zinc is an essential trace element found in every cell of your body, where it plays an important role in cellular structure, function, and metabolism. A multi-tasking mineral, zinc is required for metabolic health, immune response, reproductive health, and numerous biochemical functions. Zinc also helps preserve DNA integrity, is vital for more than 2000 transcription factors, is necessary for the production of brain neurotransmitters, and functions as an antioxidant and anti-inflammatory agent.

The Manifestations Of Zinc Deficiency

Only tiny amounts of zinc are needed for maintaining all of these functions—but it’s not uncommon to be deficient in this critical nutrient. The major manifestations of severe zinc deficiency include growth retardation, hypogonadism in males, cell-mediated immune dysfunction, and cognitive impairment. But even a mild deficit of zinc can cause significant health problems.

Because of the far-reaching influence of zinc, even a mild shortage is deleterious to numerous biochemical and immunological functions. Zinc deficiency has been linked to malabsorption syndrome, impaired wound healing, male and female reproductive problems (such has low and poor quality sperm), anemia, chronic liver disease, chronic renal disease, sickle cell disease, macular degeneration, diabetes, cancer, cardiovascular disease, skin conditions (including acne and eczema), and other chronic illnesses.

Why Zinc Deficiency Is So Common

Several factors make it challenging to get enough zinc for optimal health. The mineral isn’t stored in the body to draw upon in times of need. And it’s not easy to get enough zinc in our daily diet. Although many foods contain zinc, the only food that is an excellent source are oysters—3 ounces weigh in at an impressive 66 mg of zinc. By comparison, other good sources of zinc deliver far less: 3 ounces of grass fed beef contains only 3 mg of zinc; one cup lentils or garbanzos 2.5; one cup spinach 1.4; one quarter cup pumpkin seeds 2.5; and three quarters cup cooked quinoa 2.0. To compound the difficulty of getting enough zinc, many soils in which foods are grown are deficient in zinc.

The RDA (recommended daily allowance) of zinc for adult men is 11mg/day and for adult women 8mg/day. It’s obvious that obtaining this much zinc daily requires conscious effort and planning. But even consuming a whole-food, diverse diet leaves many people at risk of zinc deficiency. One of the problems is that although cereals and legumes contain moderate amounts of zinc, absorption is often hindered due to the phytate, calcium, and phosphate content of grains and beans. While a modest deficiency may not result in extreme manifestations such as growth retardation, it leaves us at risk for chronic, degenerative illnesses.

The Challenge Of Testing For Zinc Levels

Because zinc influences so many biochemical functions (rather than just one or two specific ones), scientists have not identified reliable biomarkers for zinc nutritional status or deficiency.

Plasma and serum zinc concentrations decline with moderate deficiency but also decrease with specific conditions including infection, trauma, stress, steroid use, and even after a meal. This is partly caused by the metabolic movement of zinc from plasma to the tissues, making it difficult to accurately determine zinc status from plasma levels.

Although there is some intra-and extra-cellular moment of zinc, I frequently test serum zinc levels and find testing to be relevant. I find that many people, especially those with compromised immune systems, have extremely low zinc levels and respond well to Naturized® zinc (25 mg. per cap). Naturized zinc is highly absorbable and does not cause the stomach upset or nausea characteristic of other forms of zinc. With aging, there is typically a decreased serum concentration of zinc and often an increased serum concentration of copper in the presence of inflammatory conditions. A common feature of several age-related chronic diseases is an increase in the copper-to-zinc ratio.1

The Many Ways Zinc Protects Cell Health

Zinc influences cellular health and cellular function in numerous ways, including:

• Zinc exerts cyto-protective influence through multiple pathways, influencing all phases of the cell cycle and playing a key role in apoptosis.3
• Zinc is integral to proteins and transcription factors that regulate cellular functions including response to oxidative stress, DNA replication, DNA repair, and cell cycle health.
• Zinc is a messenger in signal transduction and plays a critical role in gene expression. It acts as a signaling molecule both extracellularly and intracellularly. A deficiency of zinc disrupts cell signaling.4
• Zinc is a key player in regulating cell proliferation. Insufficient zinc in the extracellular milieu results in decreased activity of enzymes that regulate the cell cycle. Zinc may regulate DNA synthesis through these enzyme systems.5
• Zinc plays a major role in apoptosis, a process that initiates cell death in response to toxins and disease, and is vital to cellular homeostasis. Altered cell susceptibility to apoptosis contributes to pathophysiological changes.6
• Zinc affects hormonal regulation of cell division through its influence on the pituitary growth hormone known as IGF-1. IGF-1 mediates many cellular activities, including activation of amino acid and glucose uptake and regulation of the cell cycle.5
• Zinc contributes to multiple biological processes including gene expression, DNA synthesis, enzymatic catalysis, hormonal storage and release, neurotransmission, memory, and the visual process.6
• Zinc is a coenzyme for the enzymes that support anabolism of the polyunsaturated long-chain fatty acids (linoleic and linolenic acids), which are part of the neuronal membrane. Studies indicate that zinc may be beneficial in the treatment of children with ADHD.7
• Zinc exerts cyto-protective influence in the liver through its capacity to inhibit free radical formation and prevent lipid peroxidation. It influences the metabolism of nutrients and steroids in the liver.8

Zinc and Immune Health

Zinc is well known for the significant role it plays in immune response and immune health. It enhances both innate and adaptive immunity, is vital for immune cell function, and is crucial for the formation and modulation of inflammatory processes. Zinc is essential for immune cell development and for maintaining activity of immune cells including neutrophils, monocytes, macrophages, NK cells, B cells, and T cells.9 A deficiency leads to impaired immune function and promotes systemic inflammation.

In studies with both young adults and elderly subjects, oxidative stress markers and generation of inflammatory cytokines decreased with supplementation of zinc.10,11

Zinc, Hormones, and Prostate Health

Zinc plays a key role in prostate health, influencing immunological, infectious, and neoplastic developments. Zinc also plays an essential role in the formation of hormone receptor proteins and the nuclear binding of androgen receptors. It influences the synthesis and secretion of hormones including LH (luteinizing hormone) and FSH (follicle-stimulating hormone), both of which are necessary for the production of sperm.

The total zinc concentration in the prostate is about ten times that in other soft tissues, and a significant decrease in tissue zinc levels is seen in prostate disease.12-14 Studies find that zinc concentrations in malignant prostate tissues are only 10% to 25% of those in normal prostate tissue.15This suggests that zinc homeostasis in the prostate is essential to prostate health, although the exact mechanisms are unclear.

One theory proposes that dysregulation of zinc transporters in the prostate leads to disruption of zinc homeostasis and contributes to the formation of malignancies. Low intracellular zinc is often found in human prostate cancer tissues or in prostate epithelial cancer cell lines.14,15

Studies show that healthy zinc levels are found to inhibit NF-kB (nuclear factor kB) activation in human prostate cancer cells. This sensitizes the cells to TNF (tumor necrosis factor) mediates apoptosis, and downregulates expression of VEGF, IL-8, and metalloproteinase-9 factors.16

Zinc Deficiency, DNA Damage, and Cancer Risk

Although many dietary compounds have been suggested to contribute to the prevention of cancer, there is strong evidence to support the fact that zinc may be of particular importance in host defense against the initiation and progression of cancer.

Zinc plays a critical role in transcription factor function, antioxidant defense and DNA repair. Dietary deficiencies in zinc can contribute to single- and double-strand DNA breaks and oxidative modifications to DNA that increase risk for cancer development.17

Low zinc levels in blood and tissues and dysregulation of zinc transporters and zinc transport proteins are implicated in many types of cancer including prostate, head and neck, breast, gall bladder, lung, and colon, among others. Many studies show the relationship between zinc status and cancer; for example, a meta-analysis of 19 studies involving an estimated 400,000 participants found that the level of zinc intake was inversely associated with digestive tract cancers, especially colorectal cancer.18

In cancer patients, zinc improves cell mediated immune functions and also acts as an antioxidant and anti-inflammatory agent. It

enhances natural killer (NK) cell activity and IL-2, is involved in PG regulation, and inhibits NF-kB. Because zinc is intimately involved in immune function, zinc status also correlates with the number of hospital admissions and incidence of infections in cancer patients.

Zinc and Healthy Aging

The natural aging process is associated with multiple changes that influence molecular and epigenetic mechanisms. Changes commonly seen in the elderly include increased oxidative stress, decreased immune response, and systemic low-grade chronic inflammation.

A significant percentage of the elderly population is zinc deficient due to inadequate intake along with a natural decline in zinc associated with aging. Zinc deficient patients are found to have an increased incidence of congestive cardiopathy, respiratory infections, gastrointestinal disease, depression, and decreased immune function.

Studies show that zinc supplementation can help support immune response and healthy aging in the elderly population.19,20 In studies with elderly subjects, zinc supplementation was found to decrease incidence of infections, increase plasma zinc, and decrease TNF (tumor necrosis factor) and oxidative stress markers.21

Zinc has also been shown to enhance cognitive performance, stress response, and mood in the elderly.22 Other studies show that zinc supplementation helps reduce progression of age-related macular degeneration.23

The Most Effective Form of Zinc

In the infinite wisdom of nature, whole foods contain a complex array of vitamins, minerals, phytochemicals, enzymes, and other beneficial compounds. These essential nutrients and cofactors enhance cellular health, cell signaling, enzyme system response, and other activities that support physiological homeostasis. Naturized® whole food nutrients are delivered in the context of a whole food matrix that facilitates their bioavailability.

This matrix includes peptide carriers and cofactors naturally occurring in foods that act as chaperones, delivering nutrients to the cells and tissues of the body. Human physiology is designed to obtain nutrients from plants and natural foods. Naturized® nutrients are designed to emulate whole foods while delivering a higher concentration of specific vitamins or minerals.

Zinc (Naturized®) from S. cerevisiae offers excellent bioavailability via a food matrix that facilitates delivery into the cells for utilization. This biological source of zinc is also rich in proteins, peptides, and amino acids.

Laboratory studies have found zinc-enriched yeast (ZnY) to be 3.7 times more bioavailable than zinc gluconate.24 Other studies show ZnY to be significantly more bioavailable than zinc chelate and zinc orotate.25 In human studies, the net zinc balance in healthy humans, as measured through collection of urine, blood, and fecal samples, was significantly higher in those taking ZnY than in those taking zinc gluconate salts.26

Minerals have complex interrelationships in the human body and an excess or deficiency in one mineral can have an adverse influence on mineral homeostasis. For example, studies show that diets high in calcium can reduce zinc absorption and levels.27 While zinc is non-toxic, excess zinc consumption (over 40mg/day for adults) can upset physiological mineral homeostasis and contribute to copper deficiency.28 Zinc also influences metabolism of vitamin A, including absorption, transport, and utilization through several pathways.29

For optimal health, I recommend a diet of whole foods—and I also recommend supplements made from whole foods. In my clinical practice, I’ve observed that most people benefit from supplementing with Naturized® zinc at a dosage ranging from 25-100 mg per day. However, whenever the dosage level exceeds 50 mg per day, it is essential to monitor zinc levels to avoid creating imbalances in other nutrients.

References:

1. Malavolta M, Piacenza F, et al. Serum copper to zinc ratio: Relationship with aging and health status,Mechanisms of Ageing and Development, Volume 151, November 2015, Pages 93–100.
2. John E, Laskow TC, et al. Zinc in innate and adaptive tumor immunity. J Translational Medicine. 2010. 8:118.
3. Franklin RB, Costello LC. The important role of the apoptotic effects of zinc in the development of cancers. J Cell Biochem. 2009 April 1. 106(5):750-757.
4. Alam S, Kelleher SL. Cellular mechanisms of zinc dysregulation:
a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer. Nutrients. 2012. 4:875- 903. doi:10.3390/nu4080875.
5. MacDonald RS. The role of zinc in growth and cell proliferation. J Nutr. 2000. 130:1500S-1508S.
6. Truong-Tran AQ, Ho LH, et al. Cellular zinc and the regulation of apoptosis/gene-directed cell death. J Nutr. 2000. 130(5S Suppl):1459S- 1466S.
7. Dodig-Curkovic K, Dovhanj J, et al. The role of zinc in the treatment of hyperactivity disorder in children. Acta Med Croatica. 2009 Oct. 63(4):307-313.
8. Om AS, Chung KW. Dietary zinc deficiency alters 5a-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. J Nutr. 1996 January. 842-848.
9. Haase H, Rink L. Multiple impacts of zinc on immune function. Metallomics. 2014 Feb 17.
10. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008 May-Jun. 14(5-6):353-7. doi: 10.2119/2008-00033.
11. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug. 68(2 Suppl):447S-4463S.
12. 
12. Gomez Y, Arocha F, et al. Zinc levels in prostatic fluid of patients with prostate pathologies. Invest Clin. 2007 Sep. 48(3):287-294.
13. Prasad AS, Mukhtar H, et al. Dietary zinc and prostate cancer in the TRAMP mouse model. J Med Food. 2010 Feb. 13(1):70-76.
14. Song Y, Elias V. Marginal zinc defciency increases oxidative DNA damage in the prostate after chronic exercise. Free Radical Biology & Medicine. 2010. 48:82-88.
15. Yan M, Song Y, et al. Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. J Nutr. 2008. 667-673.
16. Uzzo RG, Leavis P, et al. Zinc inhibitis nuclear factor-kB activation and sensitizes prostate cancer cells to cytotoxic agents. Clinical Cancer Research. 2002 November. (8):3579-3583.
17. Ho E. Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem. 2004 Oct;15(10):572-8. Review.
18. Li P, Xu J, Shi Y, Ye Y, Chen K, Yang J, Wu Y. Association between zinc intake and risk of digestive tract cancers: a systematic review and meta-analysis. Clin Nutr. 2014 Jun;33(3):415-20. doi: 10.1016/j.clnu.2013.10.001. Review.
19. Haase H, Rink L. The immune system and the impact of zinc during aging. Immunity & Aging. 2009. 6:9.
20. Wong CP, Ho E. Zinc and its role in age-related inflammation and immune dysfunction. Mol Nutr Food Res. 2012 Jan. 56(1):77-87. doi: 10.1002/mnfr.201100511. Epub 2011 Nov 11.
21. Prasad AS, Beck FWJ, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007. 85:837-844.
22. Haase H, Rink L. The immune system and the impact of zinc during aging. Immunity & Aging. 2009. 6:9.
23. Smailhodzic D, van Asten F, et al. Zinc supplementation inhibits complement activation in age-related macular degeneration. PLOS ONE. 2014 Nov. 9(11):1-10.
24. 24.Vinson JA, Tompkins TA, Agbor GA. Comparative bioavailability of mineral-enriched gluconates and yeast in rat liver after depletion-repletion feeding. Biol Trace Elem Res. 2007 Aug. 118(2):104-110.
25. Vinson JA, Bose P. Comparison of the bioavailability of trace elements in inorganic salts, amino acid chelates and yeast. Proceedings on Mineral Elements. 1981. p615-621.
26. Tomkins TA, Renard NE, Kiuchi A. Clinical evaluation of the bioavailability of zinc-enriched yeast and zinc gluconate in healthy volunteers. Biol Trace Elem Res. 2007 Winter. 120(1-3):28-35.
27. Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997 Jun. 65(6):1803-1809.
28. Oregon State University. Linus Pauling Institute. Micronutrient Information. Zinc http://lpi.oregonstate.edu/mic/minerals/zinc
29. Christian P, West KP. Interactions between zinc and vitamin A: an update. Am J Clin Nutr. 1998 Aug. 68(2 Suppl):435S-4441S.