See also:

Integrative, Complimentary and Alternative Medicine

CAM – Depression





Individual Vitamins & Minerals:

Vitamin B-12

Vitamin D

Vitamin D and Pain

Calcium (Ca)

Magnesium (Mg)



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Zinc is an essential trace mineral that is obtained in the foods you eat. Next to iron, zinc is the most common mineral in the body and is found in every cell. Recently zinc has gained attention for its role in chronic pain and depression. It is also important in the function of the immune system, taste and smell, reproduction, growth, vision, blood clotting, and proper insulin and thyroid function.


The total body zinc content ranges from 1.5 to 2.5 grams, with higher contents in men than in women. Zinc is present in all organs, tissues, fluids, and secretions, but most (> 95%) is located in the fat-free tissues, mainly in intracellular compartments. Due to the bulk of skeletal muscle and bone in the body, the zinc contents of these tissues account for the majority (~83%) of total-body zinc although zinc is particularly abundant in the central nervous system (CNS). Less than 0.2% of the total body zinc (i.e., ~3.5 mg of zinc) circulates in blood.


The mechanism whereby hormones and cytokines affect plasma zinc concentrations is not been fully understood. The total body zinc can be divided into two metabolic pools: a rapidly exchangeable pool with a turnover of about 2 weeks, and a slow pool with a turnover of about 12 months. The rapid pool includes zinc in plasma and extracellular fluid and in liver, pancreatic, kidney, and intestinal tissue. Skeletal muscle and bone are the primary components of the slow pool, which represents nearly 90% of the whole-body zinc.


Severe dietary zinc restriction (< 1 mg/day for 4 to 5 weeks) causes a marked drop (about 35%) of zinc in the rapidly exchangeable zinc pool, but has little or no measurable effect on the size of the slow zinc pool. Serum zinc concentration responds fairly rapidly (within 2 weeks) to severe dietary zinc depletion, although there is considerable inter-individual variation in this response. There is good evidence of a strong relationship between dietary zinc intake and serum zinc concentration.



Most zinc is bound to metalloproteins and is involved with enzymatic activity or structural stability.  A substantial amount of neural zinc (~10%) is found in axon terminals of neurons found almost exclusively in the cerebral cortex. There are no tissue reserves of zinc that can be released in times of increased need for zinc in response to variations in dietary zinc supply.



Zinc is essential for the function of many  enzymes , including alcohol dehydrogenase, alkaline phosphatase,  DNA and RNA polymerase and super oxide dismutase, an important enzyme involved in the production of natural cellular antioxidants.


Zinc also has antioxidant properties, meaning it helps protect cells in the body from damage caused by free radicals. Free radicals may contribute to the aging process, as well as the development of a number of health problems, including heart disease and cancer. Antioxidants can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

See Antioxidants


Risks for Zinc Deficiency

In the U.S. it is estimated that about 12% of the population is at risk for zinc deficiency and as many as 40% of the elderly due to inadequate dietary intake and reduced zinc absorption from the gut. Worldwide, zinc deficiency is significantly more prevalent in underdeveloped countries. Given zinc’s role in chronic pain, depression and the immune system, especially in the time of COVID-19, it is important to test for, and treat, zinc deficiency.


Low zinc levels may be more likely seen in the following conditions:

  1. Age >60
  2. Chronic pain, especially myofascial pain
  3. Fibromyalgia
  4. Depression
  5. Heavy alcohol use
  6. Those with anorexia
  7. Those on very restricted diets, including vegetarians
  8. Those with impaired intestinal function including malabsorption syndromes (Crohn’s disease or celiac disease)
  9. Pregnant and lactating women as well as babies entirely breast fed
  10. Sickle cell disease patients
  11. Acute diarrhea in infants and children, especially malnourished infants


Zinc and Pain – the Neurobiology

The pain process consists of 4 stages: transduction, transmission, modulation and perception. The transduction of pain consists of the initial painful event associated with the stimulation of pain receptors in the body being converted to signals that will be communicated to other nerve cells. Transmission is the process of delivery of pain signals from pain-stimulated receptors to nerves and nerve pathways to the spinal cord and then to the parts of the brain associated with pain processing.  The final endpoint of pain perception is quite complex, influenced by an individuals emotional state, memories and pain history and many other variables. Pain modulation refers to the numerous mechanisms that influence the pain process at any of these other 3 stages. Pain modulation is determined by the balance of inhibitory and excitatory influences and it is here that zinc plays a significant role in pain processing.


NMDA receptors are elements that play an important role in chronic pain, particularly as a part of the modulation process. Many medications that are useful for treating chronic pain are thought to do so via their effects on the NMDA receptor. The interaction of zinc with NMDA receptors is complex. NMDA receptors have been identified as one of the synaptic targets for zinc effects on excitatory transmission (glutamatergic neurotransmission). NMDA receptors are  composed mainly of NR1 and NR2 subunits and zinc binds to the NR2A subunit.  Zinc binding to the NR2A subunit regulates major aspects of pain processing and is significant to pain transmission, chronic pain development and zinc-induced analgesia.


In addition, zinc has a role in brain functions such as motor control and in neurological disorders. Recent studies indicate a role for zinc as an antagonist at the NMDA receptor to reduce depression. In fact, early research suggests that zinc deficiency may contribute to chronic pain and depression.


Myofascial Pain

Myofascial pain is pain arising from muscle, typically trigger points (TrPs), and the connective tissue (fascia) surrounding muscle. It frequently accompanies chronic neck and low back pain and is often a major  contributor to the impairment of quality of life and activities of daily living associated with these conditions.


A study recently published in 2016 evaluated zinc and selenium related to myofascial pain.  The results of the study identified higher levels of pain in those patients with insufficient zinc and selenium dietary intake and low levels of zinc and selenium in the blood (serum and erythrocyte). This study is the first that evaluated zinc in myofascial pain. The researchers suggested the zinc demands may be higher in those with myofascial pain due to increased inflammation and oxidative stress.


Unfortunately, the study did not address the benefit of zinc or selenium supplementation towards reducing the myofascial pain.

See Myofascial Pain and Trigger Points



A 2008 study evaluated zinc blood (serum) levels in patients with fibromyalgia (FM) and found that FM patients had lower levels of zinc and the degree of zinc deficiency correlated with the levels of reported pain.  A later study published in 2011 also revealed lower zinc levels in FM patients, along with lower Mg and Ca levels while copper levels were higher.

See Fibromyalgia


Zinc and Depression

Low dietary zinc intake is a risk factor for depression. Clinical studies suggest that zinc supplements may improve depression. Zinc has also been shown to enhance antidepressant medications and reduce the side effects associated with antidepressants.


Zinc deficiency is associated with an increase in inflammatory markers and oxidative stress which lead to abnormal regulation of glutamate transmission through NMDA receptors, a phenomenon implicated in the pathophysiology of depression.  These pro-inflammatory cytokines (proteins), and reactive oxygen species (ROS or “free radicals”) enhance the breakdown of tryptophan, the primary precursor of serotonin, a neurtransmitter important in stabilizing mood.

See Tryptophan and 5-HT


Traditional neurobiological theories of depression, such as the monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. The monoamine hypothesis of depression focuses on the imbalance of serotonin, dopamine and noradrenaline (the monamine neurotransmitters) as the mechanism of depression. Antidepressant medications such as the SSRIs (Prozac, Paxil, Zoloft etc.) and SNRIs (Cymbalta, Savella and Effexor) act on these neurotransmitter levels as a means of reducing depression. New theories of depression argue that  modulation of the glutamate neurotransmitter and its action at the N-methyl-D-aspartate (NMDA) receptor (glutamatergic system) impacts depression. It is believed that dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Medications that block the NMDA receptor, including zinc and ketamine, have antidepressive effects. It is believed that the use of NMDA receptor antagonists such as ketamine may play a role in the future managment of depression.


Zinc and the Immune System

Zinc deficiency is associated with higher corticosterone levels which is indicative of  hyperactivity of the stress system involving the brain (hypothalmus and pituitary gland) and the adrenal glands, the “HPA axis.”  This hyperactivity leads to suppression of the immune system whcih can result in greater susceptibility to infection.


Zinc and Colds

Not all studies agree, but most suggest that taking zinc lozenges or using zinc nasal spray when the first  signs of a cold appear can reduce the duration and severity of symptoms and help get over a cold faster. In one study, people who had early symptoms of a cold took either a lozenge with 13.3 mg of zinc gluconate or placebo. Those who took the zinc saw symptoms such as coughing, runny nose, and sore throat resolve faster than those who took placebo. Research hasn’t clarified what form of zinc works best for colds.


Zinc nasal sprays are controversial. Some studies have found zinc nasal sprays may help reduce cold symptoms, but other studies have found no effect. In addition, zinc nasal sprays may cause some people to lose their sense of smell.

Zinc Requirements

Humans don’t need large amounts of zinc. The recommended daily allowance (RDA) for adults is 8 – 11 mg. Zinc is not stored in the body so it must be ingested on a regular basis. It’s rare for people in industrialized countries to be seriously deficient in zinc although is not uncommon to have slightly low levels of zinc.  The NIH indicates that 20%–25% of older adults have inadequate zinc intakes. Usually taking a multivitamin along with eating a healthy diet provides all the zinc you need.



Testing for Zinc Deficiency

Serum zinc concentrations vary according to the time of day, previously consumed meals, and recent exercise or other forms of stress and may fluctuate by as much as 20% during a 24-hour period. Overnight and daytime fasting increase circulating zinc levels and infection and inflammation can decrease serum zinc levels.


The most common assessment to evaluate for zinc deficiency involves measurement of plasma zinc levels, a simple blood test. The accuracy of plasma zinc levels in assessing for deficiency may be compromised by the presence of infection, liver disease, cancer, acute stress and pernicious anemia as well as recent use of oral supplements within 24 hours. Plasma zinc levels may also be insensitive to marginal deficiency because a change in plasma zinc does not occur until zinc intake is extremely low so a patient with ‘normal’ results may still be deficient.


Zinc status may also be assessed by measurement of zinc in hair and red blood cells. Hair and red blood cell levels turn over slowly, however, so these zinc levels will not reflect recent changes with respect to zinc status while monitoring replacement treatment.

The optimal range of plasma zinc is 13.8 – 22.9μmol/L (90-150μg/dl).

Symptoms of Zinc Deficiency

Symptoms of zinc deficiency also include poor or lack of taste or smell, loss of appetite, weight loss and poor wound healing. Skin problems reported to occur or worsen with zinc deficiency include white spots on the fingernails, acne, atopic dermatitis and psoriasis. Other symptoms of zinc deficiency may include hair loss, lack of menstrual period, and poor night vision. Zinc deficiency can lead to impotence and hypogonadism in males.


 – Clinical signs of zinc deficiency may occur when plasma zinc concentrations drop below 9.9μmol/L(65μg/dl).

 – Values less than 5μmol/L (33μg/dl) are likely associated with loss of the senses of taste and smell, abdominal pain, diarrhea, skin rash, and loss of appetite.

To minimize artifact, it is recommended that the patient remain in a seated position for the blood-drawing procedure, and the tourniquet should be placed for a standardized length of time (preferably less than 1 minute). Collection of morning fasting samples has been proposed as a standardized approach.


Foods Rich in Zinc

Flesh foods are rich sources of zinc, whereas plant-based diets often contain high levels of phytic acid and dietary fiber, components known to inhibit dietary zinc absorption. The best sources of zinc are oysters (richest source), red meats, poultry, cheese (ricotta, Swiss, gouda), shrimp, crab, and other shellfish. Good plant sources of zinc include legumes (especially lima beans, black-eyed peas, pinto beans, soybeans, peanuts), whole grains, miso, tofu, brewer’s yeast, cooked greens, mushrooms, green beans, tahini, pumpkin, and sunflower seeds. Due to the presence of phytates in plants which block absorption of zinc, plants may not provide enough accessible zinc which can lead to deficiency.


Oysters and Shellfish

By far the best source of zinc is oysters, whether raw or cooked. One medium size oyster contains about 5.3 mg, half of the RDA. Oysters are also high in protein, relatively low in calories, and contain many other important vitamins and minerals, including vitamin C, vitamin B-12, iron, and selenium.



One pound of boiled crawfish contains about 6.4 mg of zinc, more than half the RDA. Crawfish are packed with protein and contain no carbohydrates. A 5-ounce serving of crawfish contains close to 25 grams of protein. They are also rich in other minerals such as calcium, magnesium, iron, potassium and especially phosphorous and selenium. Crawfish are low in saturated fat and total fat, with a 5-ounce serving containing less than 1/2 gram of saturated fat. However, crawfish are high in cholesterol.with a 5-ounce serving contains close to 200 milligrams.


Crab and Lobster

Crab and lobster are also excellent sources of zinc. A 3-ounce serving of Alaskan king crab has 43 percent (6.5 mg), and lobster provides 23 percent (3.4 mg), of the recommended daily value. 


Absorption of Zinc

Zinc from animal sources such as red meat, fish, and poultry is more readily absorbed by the body than zinc from plant foods due to the presence of phytates in plants that inhibit absorption.  Zinc is best absorbed when taken with a meal that contains protein. The intestines absorbs 20 – 40% of the zinc present in food. 

Supplemental Forms of Zinc

Zinc supplements are available in several forms. Zinc sulfate is the least expensive form, but it is the least easily absorbed and may upset the stomach. More easily absorbed forms of zinc include zinc picolinate, zinc citrate, zinc acetate, zinc glycerate, and zinc monomethionine. If zinc sulfate causes stomach upset, try another form. There are also nasal sprays purported to reduce nasal and sinus congestion, although they have been reported to possibly damage the sense of smell.


The amount of elemental zinc is listed on the product label (usually 30 – 50 mg). To determine the amount to take in supplement form, remember that the RDA is about 11 mg/day from food.


Zinc Side Effects and Toxicity

Because of the potential for side effects and interactions with medications, dietary supplements should be taken with the supervision of a knowledgeable health care provider.


Research has shown that supplementing less than 40 mg/day is safe, but researchers have not conclusively evaluated long-term supplementation. Common side effects of taking zinc include stomach upset, nausea, vomiting, and a metallic taste in the mouth. High doses of zinc can cause dizziness, headache, drowsiness, increased sweating, loss of muscle coordination, alcohol intolerance, hallucinations, and anemia. High doses of zinc may also lower HDL (“good”) cholesterol and raise LDL (“bad”) cholesterol. Very high doses of zinc may also weaken immune function.


Zinc reduces the amount of copper the body absorbs, and high doses of zinc can lead to copper deficiency. For this reason some clinicians recommend taking 2 mg of copper along with a zinc supplement.


Zinc Nasal Gels or Sprays.

Numerous case reports of  loss of the sense of smell, sometimes permanent, have been associated with the use of zinc-containing nasal gels or sprays.


Denture Adhesive

Zinc is present in some denture adhesive creams at levels ranging from 17–34 mg/g. While use of these products as directed (0.5–1.5 g/day) should not be of concern, chronic or excessive use can result in zinc toxicity. Such toxicity has been reported in individuals who used 2 or more standard 2.4 oz tubes of denture cream per week. Many denture creams have now been reformulated to eliminate zinc.





Nutritional Supplements – Overview:

  1.    Evaluating Supplements
  2.    Multi-Nutrient Supplements



Zinc –  Overview

  1. Zinc — NIH Fact Sheet – 2016
  2. Alterations of Hair and Nail Content of Selected Trace Elements in Nonoccupationally Exposed Patients with Chronic Depression from Different Geographical Regions – 2016
  3. Diet and cognition – Data, theory, and some solutions from the playbook of psychology – 2016
  4. Importance of Zinc in the Central Nervous System – The Zinc-Containing Neuron – 2000
  5. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. 2006 – PubMed – NCBI


Zinc – Antioxidant

  1. The antioxidant properties of zinc – 2000


Zinc – Anxiety & Stress

  1. Essential elements in depression and anxiety_PartI – 2014
  2. Essential elements in depression and anxiety. Part II – 2015
  3. A randomised trial of nutrient supplements to minimise psychological stress after a natural disaster – 2015

Zinc – Immune System

  1. Zinc & colds MedlinePlus
  2. Roles of Zinc Signaling in the Immune System – 2016
  3. Zinc and Its Transporters in Epigenetics – 2020
  4. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly – a randomized, double-blind, placebo-controlled trial – 2016


Zinc – COVID-19

  1. Lower Plasma Zinc Levels Associated With Increased Risk of Death in COVID-19 Patients – 2020


Zinc –  Deficiency

  1. Estimating the Global Prevalence of Zinc Deficiency – 2012
  2. Zinc deficiency
  3. Human Zinc Deficiency – 2000
  4. Zinc Deficiency, Excess and Supplementation- 2014
  5. Zinc Deficiency and Clinical Practice
  6. Zinc Deficiency in Health
  7. Alterations of Bio-elements, Oxidative, and Inflammatory Status in the Zinc Deficiency Model in Rats – 2016
  8. Effect of Zinc- And Micronutrient-Rich Food Supplements on Zinc and Vitamin A Status of Adolescent Girls – PubMed – 2012
  9. Use of serum zinc concentration as an indicator of population zinc status. – 2007

Zinc –  Depression

  1. Essential elements in depression and anxiety_PartI – 2014
  2. Essential elements in depression and anxiety. Part II – 2015
  3. Alterations of Hair and Nail Content of Selected Trace Elements in Nonoccupationally Exposed Patients with Chronic Depression from Different Geographical Regions – 2016
  4. Diet and cognition – Data, theory, and some solutions from the playbook of psychology – 2016
  5. Zinc in the Monoaminergic Theory of Depression – Its Relationship to Neural Plasticity – 2017
  6. Importance of Zinc in the Central Nervous System – The Zinc-Containing Neuron – 2000
  7. New Treatment Strategies of Depression – Based on Mechanisms Related to Neuroplasticity – 2017

Zinc – Diet

  1. A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations – 2017
  2. Dietary Factors Influencing Zinc Absorption – 2000
  3. Effect of dietary phytate on zinc homeostasis in young and elderly Korean women. – PubMed – NCBI
  4. Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population. – PubMed – NCBI
  5. Moving toward a plant-based diet: are iron and zinc at risk? – PubMed – NCBI
  6. Selenium and Zinc Status in Chronic Myofascial Pain – Serum and Erythrocyte Concentrations and Food Intake – 2016
  7. Impact of zinc fortification on zinc nutrition. – PubMed – NCBI


Zinc – Fibromyalgia

  1. Levels of Magnesium, Zinc, Calcium and Copper in Serum of Patients with Fibromyalgia Syndrome – 2011
  2. The relationship between serum trace element levels and clinical parameters in patients with fibromyalgia. – PubMed – NCBI
  4. Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status? – PubMed – NCBI

Zinc – Lab testing

  1. Alterations of Hair and Nail Content of Selected Trace Elements in Nonoccupationally Exposed Patients with Chronic Depression from Different Geographical Regions – 2016
  2. Laboratory diagnosis of zinc deficiency. – PubMed – NCBI
  3. Selenium and Zinc Status in Chronic Myofascial Pain – Serum and Erythrocyte Concentrations and Food Intake – 2016
  4. Zinc Diagnostic Tests….. A guide to zinc deficiency tests.


Zinc –  NMDA Antagonist

  1. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit – 2011
  2. Zinc in the Monoaminergic Theory of Depression – Its Relationship to Neural Plasticity – 2017
  3. Importance of Zinc in the Central Nervous System – The Zinc-Containing Neuron – 2000
  4. NMDA receptor antagonists for depression: Critical considerations. – PubMed – NCBI

Zinc –  Pain

  1. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit – 2011
  2. Levels of Magnesium, Zinc, Calcium and Copper in Serum of Patients with Fibromyalgia Syndrome – 2011
  3. Selenium and Zinc Status in Chronic Myofascial Pain – Serum and Erythrocyte Concentrations and Food Intake – 2016
  4. The influence of zinc deficiency on chronic pain in Sprague Dawley rats – 2020



Zinc – Toxicity

  1. Zinc Blocks Copper – Use with Extreme Caution. Copper is Essential to Life.
  2. Neuropathy & Denture Adhesive



  1. Calcium
  2. Magnesium


Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.


For more information, please contact Accurate Clinic.


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