028: Why You Should Manage Your Zinc Status and How to Do It
Mastering Nutrition Episode 28
Do you want beautiful, flawless, radiantly healthy skin? Want to stay healthy during cold season? Want to eat that bagel without your blood sugar spiking through the roof? Then it’s time to think about zinc.
Zinc is critical to every aspect of our biology, but the first things to go when we run low are our skin health, our immune system, and our glucose tolerance. Zinc, moreover, is critical to antioxidant defense, so should be considered broadly protective against all of the degenerative diseases that occur with aging.
Wait, are you too young to care about aging? No problem. You at least want healthy skin, great sex, or a lean physique, so listen up.
Zinc-rich foods are harder to come by then you’d think. Nutritional databases can be wildly inaccurate if you don’t adjust for inhibitors of zinc absorption in natural foods. And zinc supplements can be valuable, but they’re not a panacea. In fact, used wrongly, they can quickly induce a deficiency of copper and other minerals that are just as critical to your health.
There’s an easy solution to this mess: let’s master this topic, stat, with the Mastering Nutrition podcast, episode 28.
In this episode, you will find all of the following and more:
0:00:35 Cliff Notes
0:04:43 The discovery of zinc deficiency on diets of whole wheat bread with small amounts of milk and potatoes, a quarter pound of clay, and no meat: dry skin, hypogonadism, lack of secondary sex characteristics, short stature, frequent infections
0:10:28 The biochemical and physiological roles of zinc
0:12:05 Structural roles of zinc, with an emphasis on zinc finger motifs; interactions with vitamins A and D, thyroid hormone, adrenal hormones, and sex hormones
0:16:56 Catalytic roles of zinc, including the RNA polymerases that make it necessary for the production of every single thing in the body
0:19:32 Interactions with vitamin A, from transport via retinol-binding protein (RBP) through activation by alcohol dehydrogenases to retinal and retinoic acid to creating vision via rhodopsin and regulating gene transcription via DNA-binding of the retinoic acid receptor
0:22:24 Regulatory roles of zinc
0:25:28 Zinc and oxidative stress (necessity for hydrogen peroxide production in the thyroid gland and immune phagocytes, zinc release from zinc-thiolate clusters; protective effects of metallothionein exchanging zinc for other metals; negative effects of uncoupling of endothelial nitric oxide synthase [eNOS] on blood vessel function and oxidative stress
0:35:49 Regulation at the cellular level (metallothionein, MT; ZIP and ZnT transporters)
0:37:26 Regulation of metallothionein (metal transcription factor-1 [MTF-1] through the metal response element [MRE] controlled primarily by zinc but also heavy metals, antioxidant response element [ARE] via Nrf1 and Nrf2, which provides regulation by oxidative stress and copper, glucocorticoid response element [GRE] which provides regulation by adrenal hormones and inflammation
0:46:46 What happens when we eat zinc (effects of phyate, amino acids, calcium, organic acids, and iron)
0:53:55 Plasma zinc and the exchangeable zinc pool
0:55:57 Factors that affect plasma zinc status (variation according to meals, diurnal variation, stress, inflammation, menstruation)
1:03:21 Causes and effects of deficiency
1:07:25 Variations in soil zinc
1:08:43 Balance of animal protein and phytate in the diet
1:12:03 Causes and effects of toxicity (especially with respect to copper deficiency)
1:20:20 What is the best marker of zinc status?
1:30:03 Copper deficiency markers as the most sensitive markers of zinc excess
1:31:15 Dietary strategies (animal foods, especially oysters, red meat, and cheese; soaking, sprouting, and fermenting to neutralize phytate)
1:40:35 Zinc supplementation on a plant-based diet (especially relevant to vegan diets but also to vegetarian diets)
1:35:28 Supplementation of zinc (What form? Citrate, acetate, gluconate, picolinate, oxide? What dose? When to take it?)
1:37:35 Recommendations for timing of diet and supplements across the day for best absorption
1:40:00 Wrapping up
Signs and Symptoms of Zinc Deficiency
The most sensitive sign of zinc deficiency is patches of dry skin.
As the deficiency progresses, skin lesions can become more severe, eventually resulting in severe acne or blisters and pustules. Other signs include poor glucose tolerance, poor wound healing, increased risk of infections resulting in sore throat or diarrhea, declining cognitive function, poor appetite, and an increased number of calories needed to sustain lean mass. Given the last two problems, weight loss is likely to occur, with the majority of weight lost as lean mass rather than fat.
Potential Causes of Zinc Deficiency
One or more of the following patterns strengthen the interpretation of a zinc deficiency:
A dietary pattern low in animals foods and high in grains, legumes, nuts, and seeds, especially if these are not soaked, sprouted, fermented, or otherwise processed to neutralize their phytate content.
Malabsorption disorders affecting the small intestine compromise zinc absorption.
Alcoholism and diabetes lead to high urinary losses of zinc.
Rarer causes include genetic mutations in zinc transporters, chelation therapies designed to detoxify other metals, and hemolysis. Hemolysis causes the zinc inside red blood cells to be released into the blood and spill into the urine, and this has been best demonstrated in sickle cell disease.
Signs and Symptoms of Excess Zinc and Zinc Toxicity
Acutely, zinc toxicity can cause gastric distress, such as nausea and vomiting, and dizziness. A high-dose zinc supplement of 50 mg or more on an empty stomach can cause this mildly, but dangerous levels of toxicity are generally found in rare cases of people eating pennies. One death has been attributed to an accidental infusion of seven grams of zinc over a 60-hour period.
Chronically, excess zinc can impair immune function and lead to copper deficiency, and perhaps deficiencies of other poorly studied minerals like molybdenum and chromium. This could lead to increased vulnerability to infections and to any of the signs and symptoms of copper deficiency outlines in the copper episode.
Potential Causes of Zinc Toxicity
Apart from rare cases of eating pennies and industrial exposures such as the galvanization of steel, the overwhelmingly likely cause of excess zinc is supplementation with high doses of zinc without sufficient supplementation of other minerals, especially copper. Zinc-rich foods are not likely culprits because they are also rich in copper and the other minerals needed to balance zinc.
Measuring and Assessing Zinc Status
I recommend using plasma zinc, which is available from LabCorp, Quest, the Genova ION Panel, or DirectLabs (for DirectLabs, go to their test search page search “zinc” without the quotes, and scroll to “Zinc, Plasma or Serum.”
Plasma zinc must be taken after an overnight fast. For men, it should be above 740 micrograms per liter (ppb) or 0.74 μg/mL. For women, it should be above 700 μg/L (ppb) or 0.7 μg/mL. However, the sweet spot may be closer to 1000. Plasma zinc plateaus in response to a robust zinc intake somewhere around 1200 μg/mL, and I would not worry if plasma zinc is high within the normal range.
Plasma zinc is decreased by inflammation, oxidative stress, the ovulatory and luteal phases of the menstrual cycle, probably pregnancy and oral contraceptive use, and any kind of stress that leads to an adrenal output. For this reason I would not be too quick to interpret asymptomatic movements toward the low end of the reference range as a zinc deficiency. However, low or borderline low plasma zinc is a strong indicator of zinc deficiency when combined with one or more of the deficiency signs and one or more of the potential causes listed above.
Plasma zinc can not be used to monitor zinc toxicity. I would look primarily for low serum copper (LabCorp, Quest) and, as a secondary measure, low superoxide dismutase activity on the Genova Oxidative Stress 2.0 Panel.
Note that the Genova ION Panel offers plasma copper and zinc together, and Direct Labs offers them together from either plasma or serum. (For Direct Labs, go to their test search page search “zinc” or “copper” without the quotes, and scroll to “Copper and Zinc, Plasma or Serum.”) Unfortunately, zinc is best measured from plasma and copper is best measured from serum. It is therefore preferable to measure them separately in their ideal forms for the clearest interpretation.
How Much Zinc Do We Need?
The RDA was set on the basis of preventing net loss of zinc from the body over time, not on the basis of optimizing health. Nevertheless, it provides a good starting point.
The RDA begins at 3 milligrams per day (mg/d) in the first three years of life. Children four to eight years old need 4 mg/d. For children who are between 9 and 13 years old, this doubles to 8 mg/d.
After the age of 14, the RDA differs for males and females. For males, it increases to 11 mg/d and stays there throughout life. For females, it increases to 9 mg/d, drops to 8 mg/d when they turn 18. At any age, the RDA increases to 11 mg/d during pregnancy and 12 mg/d during lactation.
All of this variation is driven by two principles: 1) zinc needs are determined largely by lean body mass, 2) children who are growing and women who are providing zinc to a growing fetus or a nursing baby must supply extra zinc to meet the needs of growth.
Although not addressed in the RDA, males should probably add 3 mg to their requirement for each ejaculation.
Bodybuilders should probably add 90 total milligrams of zinc for every ten poundsof lean body mass they want to add divided by the time over which they will add it, multiplied by 3 to account for partial absorption of zinc from food. In other words, if you want to put on ten pounds of lean mass in one month, divide 90 mg by 30 days to reach an added zinc requirement of 3 mg/d. This is what you need to absorb, and the amount of zinc from food you need to eat would, on average, be somewhere around 9 mg/d during the period in which you are adding the lean mass. Once the lean mass is added, you no longer need the extra zinc.
During an acute crisis of diarrhea, the dose of zinc should be doubled.
Getting zinc over and above the zinc requirement through natural foods or low-dose supplements may be helpful for optimizing skin health, immunity to infectious disease, and glucose tolerance. It may also help optimize antioxidant defense, which decreases the wear and tear the body suffers over time and the risk of degenerative diseases that occur with aging.
What Foods Are the Best Sources of Zinc?
The principle inhibitor of zinc absorption is phytate, so the best zinc sources are those that are richest in zinc and lowest in phytate. Among plant foods, the best sources of zinc are whole grains, legumes, nuts, and seeds, but these are also the richest sources of phytate. Thus, animal foods are better than plant foods as sources of zinc across the board.
Oysters take top place, with 30-180 milligrams per 100 gram serving, depending on the variety. Red meat is richer in zinc than other meats. For example, beef has 5-10 mg, whereas chicken has 1-5 mg, and salmon generally has less than 1 mg. Milk has 1 mg/cup, but cheese concentrates the zinc-rich fraction. In a 100 g serving, cheese generally has at least 1 mg and usually 3-4 mg. Eggs usually have a little over 1 mg, making them comparable to fish.
Thus, the best sources of zinc are oysters, red meat, and cheese, sorted in that order. Most other animal foods make important contributions, but don’t stand out as superfoods.
You could meet the RDA by consuming one or two oysters, one or two servings of beef, or two to three servings of cheese. Zinc is best absorbed when spread evenly across meals and when consumed away from phytate.
Among plants, whole grains, legumes, nuts, and seeds generally have amounts of zinc that are roughly equivalent to the variation found in chicken. However, the phytate in these foods makes the zinc less bioavailable. By some estimates, you need 50% more zinc when obtaining it from these foods. By other estimates, you need ten times more zinc. Soaking, sprouting, or fermenting them can neutralize about half the phytate, making the zinc more bioavailable. Nevertheless, I think it is wise to take a zinc supplement if you are eating a mostly or exclusively plant-based diet.
Which Forms of Zinc Should I Take as Supplements?
The best-studied forms of zinc are gluconate, acetate, sulfate, and citrate. All of these have excellent absorption. Zinc picolinate and zinc oxide are not as reliable. Other forms have not been studied as well, but methionine chelates are probably very bioavailable. I recommend using supplements that come in 10-20 mg per serving. Doses of 25-30 mg are probably safe on the background of a diet rich in copper and other minerals, but unnecessary. Doses of 50 mg can cause nausea when taken on an empty stomach, are rarely needed, are likely to exceed the capacity to absorb zinc by a large degree, and likely to induce a copper deficiency.
The simplest way to get a low-dose zinc supplement balanced with a reasonable amount of copper is to use Jarrow Zinc Balance. The zinc comes as chelate of methionine. This is not as well studied as the other forms in its ability to replete a zinc deficiency, but we’ve known for decades that methionine enhances zinc absorption, so I think it is trustworthy. It has a 15:1 ratio of copper. I would have shot for 10:1, but I think 15:1 is adequate, especially in the context of a copper-rich diet. It costs $7.19 per bottle of 100. Taking one a day, a bottle will last you a little over three months and cost you 7 cents per day. On Amazon, you can use the “subscribe and save” feature to save 5%, which is pretty negligible, but you can subscribe to five or more products and push the price down by 15%. Across five products, that would become meaningful. If you don’t want a subscription, make sure the “subscribe and save” button isn’t clicked.
The most cost-effective zinc supplement I can find out of the ones I like is Natural Factors 15 mg Zinc Citrate. It is significantly less expensive at iHerb ($5.57) than on Amazon ($8.57). A bottle has 90 tablets, lasting three months, and costing 6 cents per day. It is probably safe to take one a day with no extra copper if your diet is rich in copper, but if taking two per day I would add one tablet of Solgar copper glycinate.
Thus, while zinc citrate is a little less expensive and I’m modestly more confident in its absorption, the Jarrow Zinc Balance becomes more cost-effective when its copper content is considered, and is attractive for its simplicity.
Please note that these are fundamentally different principles than those that dictate what a good zinc lozenge is to kill a cold. My episode on zinc acetate lozenges covers those principles in detail.
What Dose of Zinc Supplement Should I Take and When Should I Take It?
Zinc supplements are best taken on an empty stomach. Wait at least three hours after your previous meal, and take it at least one hour before your next meal. For example, wake up, take the zinc, wait an hour, then eat breakfast. Or, eat breakfast, wait three hours, take the zinc, wait an hour, then eat lunch.
If taking more than one tablet or capsule per day, take them in divided doses. For example, take one an hour before breakfast and the other an hour before dinner.
10 mg/d of zinc on an empty stomach is sufficient to prevent or reverse a deficiency, but this should be doubled in an acute crisis of diarrhea or with chronic intestinal malabsorption.
If you eat a lot of zinc-rich foods and do not have any signs of zinc deficiency, you probably don’t need a supplement. If you don’t eat a lot of zinc-rich foods, or if most of your zinc-rich foods are plant foods, I recommend taking 15 mg/d as a preventative measure.
For chronic infection and inflammation, diabetes, alcoholism, and rare disorders that lead to zinc deficiency independent of diet, you may need larger doses, but I recommend working directly with a health care practitioner to carefully monitor zinc status and the efficacy of an individually tailored supplementation regime.
An acceptable zinc-to-copper ratio is somewhere between 2:1 and 15:1 in favor of zinc. On the background of a copper-rich diet, 15 mg/d of zinc probably doesn’t matter. But at doses higher than this, I would supplement with copper at an approximately 10:1 ratio (give or take). At doses higher than 30 mg/d, I would strongly consider supplementing with a low-dose mixed trace mineral supplement, such as a single serving per day of ConcenTrace.
Zinc Status Links and Research
The zinc chapter of Modern Nutrition in Health and Disease is a great starting place for anyone who is scientifically inclined. This is one of the few textbooks I was required to purchase in school and found so useful I kept as a cherished reference. When the most recent edition came out, I bought the Kindle version, which is incredibly easy to navigate and take notes from compared to the hardcover version of the previous addition that I also still have.
Dietary Reference Intakes for Zinc, which provides the rationale for the RDA and upper limit.
Ananda Prasad played a key role in the discovery of zinc as an essential nutrient in humans, and wrote this review in 2014: Impact of the discovery of human zinc deficiency on health.
Zinc and its importance for human health: an integrative review
Methods of Assessment of Zinc Status: A Systematic Review
Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review.
Assessment of Zinc Status, a review from 1990.
The relationship between zinc intake and serum/plasma zinc concentration in adults: a systematic review and dose-response meta-analysis by the EURRECA Network.
A review on the response of circulating zinc to inflammation.
Protective effects of 45 mg/d zinc in the elderly (paper 1)
Protective effects of 45 mg/d zinc in the elderly (paper 2)
The AREDs study used poorly absorbable high-dose zinc and poorly absorbable low-dose copper, with decreases in age-related macular degeneration and loss of visual acuity but an increase in self-reported anemia.
50 mg of zinc/d lowers superoxide dismustase, suggesting a negative effect on copper status.
The effect of phytate on zinc absorption may be massively underestimated.
Phytate in foods and methods to reduce it.
Dietary factors influencing zinc absorption.
Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans.
Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.
Vegetarian diets and zinc status.
Mammalian Metallothioneins: properties and functions
Metallothioneins, unconventional proteins from unconventional animals: a long journey from nematodes to mammals.
The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective.
The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription.
Magnesium and zinc status during the menstrual cycle.
Experimental zinc depletion in humans (paper one)
Experimental zinc depletion in humans (paper two).
Zinc and its interaction with insulin signaling
This is part of a series on managing nutritional status where all of the episodes are collated on the show notes page for the introductory post, What Makes a Good Marker of Nutritional Status?
Out of that series, the copper episode is most related to this episode.
The episode on zinc acetate lozenges covers a fundamentally different principle of the ability of these lozenges to kill colds. This should not be confused with the principles of improving zinc nutritional status in this episode.
Since zinc is a fundamental component of the antioxidant system, my 14-lesson video series on the antioxidant system will help place much of the content of this episode in its proper context.
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