We all know that hydration is important, especially as the weather warms up and we spend more time outside. But when it comes to getting our eight glasses of water a day, there are numerous options, with some claiming to be better than others. But is there any real difference? We took a look at 10 different kinds to see which hold water.

1. Tap
The water that comes out of your kitchen faucet (and bathroom faucets, toilets, garden hose, washing machine, etc.) comes from the local water supply and can be potable. However, when it comes to drinking water, a growing number of people choose alternative sources based on fear of what’s in the local water supply or their own research.1,2

The Environmental Working Group analyzes state water tests and provides reports on local water supply based on ZIP code. However, it’s worth noting that legal limits for water contaminants can be 20 years old and do not necessarily indicate safety.3 Tap water can contain bacteria, pesticides, unhealthy levels of minerals, lead, and other contaminants, including glyphosate.1-4

Many people who don’t want the added plastic waste (as well as the convenience) choose to invest in filtrations systems. These can range from simple and inexpensive activated charcoal water filters, like Brita® filters, to more expensive reverse osmosis filtration systems. 

2. Purified
Purified water takes ground water or the water that comes from your tap and treats it to remove the impurities such as chemicals, bacteria, and other contaminants. There are several ways this is done, including reverse osmosis (see #3 below) and through ion exchange.5 In order to be designated as purified, the treated water must follow EPA regulations for drinking water, meaning that it may have no more than 10 ppm of solids like calcium, sulfate, heavy metals, ammonia, and other substances, and its pH must be in the range of 5–7.5
The downside to purified water is that along with the removal of harmful substances, minerals such as fluoride, which is commonly added to tap water, is removed as well.

3. Reverse osmosis
Reverse osmosis uses ultrathin membranes to filter impurities out of tap water cost-effectively.6 Studies are being done regularly on new materials for these membranes, but it is clear that this system of purification is effective for the removal of numerous microbial contaminants, as well as other organic compounds.6,7
As with other purified water options, reverse osmosis also removes beneficial minerals from the drinking water. In addition, the system must be monitored and cleaned regularly to ensure the membranes are not degraded and are filtering properly.7

4. Distilled
An older type of purified water, distilled water is made by boiling water; the steam is then condensed back into a liquid to remove any impurities. As with other types of purified water, minerals are also removed in the distillation process.8 While it is safe to drink distilled water, it shouldn’t be the only source of drinking water.
That said, distilled water has many useful purposes. Since it is so pure, distilled water is an inexpensive and convenient option for numerous household uses including in steam irons, automobiles, and humidifiers.

5. Spring/glacial
Many bottled waters claim to be bottled at the source, usually a natural spring or glacier. Springs are formed when flowing ground water finds its way to the surface, whether through natural or man-made means.8 Since the sources, means of access, and initial water quality can vary greatly, the resulting bottled water may contain safe mineral levels but may also contain microbes, bacteria, and pollutants.9
Similarly, glacial water quality depends on the source and may contain contaminants above safe levels.10

6. Mineral
A specific kind of spring water, mineral water comes from mineral springs or underground reservoirs that contain at least 250 ppm of minerals and trace elements such as magnesium, calcium, potassium, and sodium, minerals the body can’t make itself.11,12 Mineral water may be treated to remove contaminants or to add carbon dioxide, although some mineral water naturally contains CO2 from its source.11

7. Sparkling
Like mineral water, sparkling water contains carbon dioxide and is often sold as soda water, seltzer water, or club soda. It can be a lower-calorie alternative to soda for those who prefer their water to be fizzy. The carbonation may be added naturally or artificially, and sparkling water may or may not contain minerals, also either naturally or artificially added.13

Be sure to look at labels, since some flavored sparkling waters have added sugars.

8. Alkaline
One of the latest trends in drinking water is alkaline water. Alkaline water gets its name from its pH level, which is higher than normal tap water. On a scale of 14, tap water tends to sit right in the middle, with a pH level ranging from 6.5 to 8.5.14 Alkaline water’s pH level can range from slightly to significantly higher.
In addition, alkaline water contains minerals such as calcium, magnesium, sodium, and potassium. These alkaline minerals give alkaline water antioxidizing properties.15

Alkaline water tends to have a bitter taste and can cause deposits in pipes if the tap water is naturally alkaline.16

You may have read claims that alkaline water is better for you because it helps to neutralize acid in the body. It is said to provide better hydration and reduce gastrointestinal issues. However, while adding antioxidant-rich foods to your diet is healthy, your body has its own ways of keeping a neutral pH level. In fact, moving your levels too far on either end of the pH scale can be unhealthy.17 The stomach’s acidity level is ideal for killing off harmful bacteria; neutralizing it can have adverse effects. Drinking too much alkaline water can cause skin irritations, nausea, and vomiting.18
​
A few studies have been done that claimed an alkaline-rich diet may support bone health and healthy blood pressure levels and help increase blood oxygen levels, but the studies were very small, and there is little evidence to support these claims.16 Note that an alkaline-rich diet is not the same as drinking alkaline water. There are components in an “alkaline diet” (such as it being more plant-based) other than pH that may contribute to beneficial effects.

9. Well
Back in the day, many people got their drinking and cooking water from wells. But even though tap water is easily accessible for most of us, approximately 13 million homes still get their drinking water from private wells.19 Well water is ground water accessed by drilling and then brought to the surface through a pump system. As with other ground water sources, well water may contain any number of minerals or impurities, but as well water is not regulated by the EPA, well owners are responsible for testing and treating the water and for assuming any risks.19

10. Vitamin
Some bottled water companies have started selling vitamin-infused water as a “healthier” alternative to plain bottled water. While it is a simple alternative for those who don’t follow a nutritious diet or prefer not to take supplements in pill form, vitamin water can problematic for a couple of different reasons.
To start with (and as a general rule for any flavored beverage), check that label. Some bottled vitamin waters contain added sugar to make it more palatable. In addition, while some contain a small amount of electrolytes that can help replenish what’s lost during exercise, these products tend to contain vitamins people are rarely deficient in.20

All this talk of water may have you feeling thirsty. So when you reach for a glass or bottle, which water will you choose to fill it?

By Melissa Blake, ND
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Withania somnifera (ashwagandha) is an important Ayurvedic herb with a long history of use.1
Also known as “Indian winter cherry” or “Indian ginseng,” this beloved herb was traditionally made into a fine powder then mixed with water, milk, ghee, or honey and consumed to promote youth and longevity.1
As an herb with a wide range of potential benefits, ashwagandha has become a popular adaptogen found in many supplement formulas.

What is an adaptogen?
An adaptogen is a classification given to herbs that have a positive impact on the stress response. In other words, they help you adapt to, or cope with, stress. Ashwagandha is one of the most well-known and best-studied herbal adaptogens.

Studies in animals exposed to environmental stress (cold water) and physical stress (endurance swimming) were better equipped to handle the stress and less likely to experience stress-related consequences when taking ashwagandha.1 They were better able to adapt. Point: ashwagandha.
Being able to swim in cold water for a long time is a type of stress that is less relevant to humans; however, studies in humans have also highlighted ashwagandha’s adaptogenic properties in ways that matter to us. Participants taking ashwagandha root extract for 60 days reported significant reduction in perceived stress and improvements in general health.2 These are important outcomes, because much of our day-to-day stress is related to our perception of it. If we perceive less stress, we have less stress. Ashwagandha scores again.

Studies have also linked ashwagandha with overall lower levels of cortisol.2 Cortisol, often referred to as the “stress hormone,” works best when it is not too high and not too low. High levels of cortisol have been associated with food cravings and an increase in appetite.3

Did you say an increase in appetite?

Hmmm. Stress-eat, anyone?
​
Stress eating is an all too frequent way many people cope with high levels of stress, and indulging in too much steamed broccoli is not usually the problem! Stress eating is more often associated with high intake of calorie-rich, nutrient-poor foods (cookies, potato chips, chocolate, you get the picture) and may contribute to weight gain. When you feel stressed, you also feel less like exercising. Can you relate? Double-wham.

A study evaluated the benefits of ashwagandha on various stress-related parameters, including food cravings and body weight. After 8 weeks, there was a significant reduction in perceived stress, improvement in self-reported well-being and happiness, fewer food cravings, and even a reduction in body weight.3 Ashwagandha for the win.

These results are especially important because they highlight how pervasive stress can be. Too much or poorly controlled stress has the potential to wreak havoc on every system in our bodies.2,3 Even short-term stress can negatively influence mood, sleep, and appetite levels.3 Poorly managed stress that occurs over a long period can decrease immune health.4 Improving the body’s ability to cope and reducing some of the negative consequences associated with stress is a pretty big deal.

Ashwagandha has a long history of use. Although animal studies outweigh human trials, evidence suggests this herb as a safe and effective way to support a healthy stress response. Talk to your healthcare provider about how you can include adaptogens such as ashwagandha into your personalized stress resilience plan.

References:

1. Singh N et al. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5):208-213.
2. Chandrasekhar K et al. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34(3):255-262.
3. Choudhary D et al. Body weight management in adults under chronic stress through treatment with ashwagandha root extract: a double-blind, randomized, placebo-controlled trial. J Evid Based Complementary Altern Med. 2017;22(1):96-106.
4. Schakel L et al. Effectiveness of stress-reducing interventions on the response to challenges to the immune system: A meta-analytic review. Psychother Psychosom. 2019;88(5):274-286.

by Erik Lundquist, MD

Looking for ways to support healthy immune function? Erik Lundquist, MD shared a variety of options to consider as ways to help support immune health.
Here are some formula recommendations he gives to his patients:

Vitamins:

• Vitamin D3: 4-5,000 IUs per day or as directed by your healthcare practitioner (Dr. Lundquist recommends D3 5000 or D3 10,000 + K; these high-potency formulas provide vitamin D (as D3) for greater absorption*).
• Vitamin C: 1,000 mg per day or as directed by your healthcare practitioner (Ultra Potent-C® 1000). The buffered delivery system in this formula helps prevent the potential upset sometimes associated with high vitamin C intake.*

Probiotics:

• Specifically Saccharomyces Boulardii: (UltraFlora® Acute Care or UltraFlora Spectrum)

Extracts and Amino Acids:

• Andrographis extracts (Andrographis Plus®; note that andrographis should not be taken if pregnant or breastfeeding)  
• Mushroom extracts: 1 tablet per day or as directed by your healthcare practitioner (ImmuCore®)
• Turmeric, ginger, boswellia: 2 capsules once daily or as directed by your healthcare practitioner (Inflavonoid Intensive Care®)
• N-acetyl cysteine (NAC): 750 mg, 2 tablets twice daily or as directed by your healthcare practitioner (GlutaClear®; features a blend of ingredients designed to help support the body’s production of glutathione, a primary antioxidant throughout the body*).

Keeping clean & healthy

Maintaining good hygiene helps keep the immune system healthy. Consider these simple preventative measures that should be followed routinely to ensure good hygiene practices.

1. Wash your hands. Begin by rinsing your hands with clean, running water followed by lathering with soap and scrubbing for at least 20 seconds. Rinse and dry your hands well using a clean towel.1
2. Eat a well-balanced diet, rich in beta-carotene and vitamin C but low in processed carbohydrates and simple sugars.2-4 Do not underestimate the power of a healthy diet loaded with fruits and vegetables to help you remain healthy.
3. Get adequate sleep. Did you know lack of sleep can affect both your mental and physical health?5 Sleep is as vital to our wellbeing as food, water, and air. Make sure to get 7 to 8 hours of sleep each night.
4. Manage stress. Daily meditation, restorative exercise, and strong, healthy relationships can encourage continued healthy immune function.6-8

References:

1. Centers for Disease Control. https://www.cdc.gov/handwashing/why-handwashing.html. Accessed March 25, 2020.
2. National Institutes of Health. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/. Accessed March 30, 2020.
3. Grun T et al. J Nutr. 2010;140(12):2268S-2285S.
4. Bessesen DH. J Nutr. 2001;131(10):2782S-2786S.
5. National Institutes of Health. https://www.nhlbi.nih.gov/health-topics/sleep-deprivation-and-deficiency. Accessed March 25, 2020.
6. Marchand WR. J Psychiatr Pract. 2012;18(4):233-252.
7. Basso JC et al. Brain Plasticity. 2017;2(2):127-152.
8. Giles LC et al. J Epidemiol Community Health. 2002;59(7).

By Molly Knudsen, MS, RDN
​
There’s no doubt that antioxidants are good for health. Antioxidants have been in the public spotlight since the 1990s and have only gained attention over the years, basically reaching celebrity status. And that status has not wavered, especially as their role in immune health becomes increasingly known. Antioxidants and antioxidant-rich foods continue to trend and make headlines, most recently in the forms of matcha/green tea drinks, acai bowls, golden milk, or just good ol’ fashioned fresh fruits and vegetables. Antioxidants are here to stay not only because they’re found in delicious foods, but they also play a vital role in health by protecting the body against oxidative stress.1

What is oxidative stress?

Everyone’s heard of oxidative stress, but what exactly does that refer to? Oxidative stress occurs from damage caused by free radicals. Free radicals are unstable molecules that have lost an electron from either normal body processes like metabolism, reactions due to exercise, or from external sources like cigarette smoke, pollutants, or radiation.1
Now electrons don’t like to be alone. They like to be in pairs.
So do free radicals suck it up and leave one of their electrons unpaired?
Nope. They steal an electron from another healthy molecule, turning that molecule into another free radical and, if excessive, wreak havoc in the body and its defense system.
Immune cells are particularly vulnerable to oxidative stress because of the type of fat (polyunsaturated) that they have in their membrane.2 So high amounts of oxidative stress over time can be especially detrimental to immune system.

What are antioxidants?
​
Antioxidants are the heroes that can break this cycle. And there’s not just one antioxidant. Antioxidants refer to a whole class of molecules (including certain vitamins, minerals, compounds found in plants, and some compounds formed in the body) that share the same goal of protecting the body and the immune system against oxidative stress.2 But different foods contain different antioxidants, and each antioxidant has its own unique way of supporting that goal.  

6 antioxidants for oxidative stress protection + immune health

1. Vitamin C
Vitamin C is a powerful antioxidant that also contributes to immunity. It works by readily giving up one of its electrons to free radicals, thereby protecting important molecules like proteins, fats, and carbohydrates from damage.3 Vitamin C is a water-soluble vitamin, which means storage in the body is limited, and consistent intake of this nutrient is vital. Research shows that not getting enough vitamin C can impact immunity by weakening the body’s defense system.3 Vitamin C is found in many fruits and vegetables, including strawberries, bell peppers, citrus, kiwi, and broccoli. The benefits of vitamin C’s antioxidant capabilities are more than just internal. Benefits are also seen when a concentrated source of this antioxidant is applied to the skin. For example, topical vitamin C serums are often recommended by dermatologists and estheticians to help protect the skin from sunlight and address hyperpigmentation.4

2. Epigallocatechin 3-gallate (EGCG)​

3. Glutathione
​
​Glutathione is a powerful antioxidant that the body actually makes internally from three amino acids (AKA building blocks of protein): cysteine, glutamate, and glycine.6 Not only does this antioxidant protect the body against oxidative stress, it also supports healthy liver detoxification processes.7 Glutathione levels naturally decrease with age, and lower glutathione levels in the body are associated with poorer health.8 Since it takes all three of those amino acids to form glutathione, ensuring that the body has adequate levels of all three is vital. Cysteine is the difficult one. It’s considered the “rate-limiting” step in this equation, since it’s usually the one in short supply, and glutathione can’t be formed without it.6 Cysteine contains sulfur, so foods like unprocessed meat, garlic, and asparagus are great choices to support cysteine levels. Like cysteine, the compound N-acetylcysteine (found in supplements and often labeled NAC) can also be used to support the body’s glutathione levels.6

5. Vitamin E

Vitamin E is a fat-soluble vitamin, meaning it’s best absorbed with fat. It acts as an antioxidant by stopping the production of free radicals from forming when fat is oxidized, or burned.10 Vitamin E is found in nuts and seeds (almonds, sunflower seeds, and hazelnuts) as well as green leafy vegetables. Vitamin E also plays a role in heart, eye, and cognitive health.10 

6. Quercetin
​
Quercetin is one of the most well-studied flavonoids, or plant compounds, typically found in onions, kale, broccoli, apples, and tea. Quercetin acts as a free radical-scavenging antioxidant, helps inhibit oxidative stress, and supports a healthy immune response.11

What’s the bottom line?
​
​Antioxidants are a crucial part to any healthful diet. They help protect the body from damage caused by oxidative stress and support immune function. There are many more antioxidants that are beneficial to health than those listed here. The best way to ensure that you’re getting enough antioxidants from the diet and supporting the antioxidants the body makes on its own is to consume a diet high in plants like fruits, vegetables, nuts, seeds, and legumes.

References

1. Pizzino G et al. Oxid Med Cell Longev. 2017;2017:8416763. 
2. Knight JA. Ann Clin Lab Sci. 2000;30(2):145-158.
3. Carr AC et al. Nutrients. 2017;9:1211.
4. Al-Niaimi F et al. J Clin Aesthet Dermatol. 2017;10(7):14-17.
5. Forester SC et al. Mol Nutr Food Res. 2011;55(6):844-854.
6. Minich DM et al. Nutrients. 2019;11:2073.
7. Pizzorno J. Integr Med (Encinitas). 2014;13(1):8-12.
8. Glutathione. Webmd.com. https://www.webmd.com/vitamins-and-supplements/glutathione-uses-risks. Accessed August 19, 2020.
9. Hewlings SJ et al. Foods. 2017;6(10):92.
10. Vitamin E fact sheet for health professionals. Ods.od.nih.gov. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. Accessed August 25, 2020.
11. D’Andrea G. Fitoterapia. 2015;106:256-271.

by Lewis Chang, PhD
Introduction
Fun fact: Just like us humans, oysters have a sense of hearing and dislike noises. Researchers from France and Morocco conducted an experiment by exposing oysters (in this case, Pacific oysters; n=16) to different noises emitted from underwater loudspeakers and recorded shell movements using sensors attached to the shells. Within a minute these shellfish would shut their shells, particularly when hearing low-frequency noises.1
Food fact: Oysters have the highest amount of the mineral zinc per serving in any food. According to the US Department of Agriculture’s FoodData Central, one raw Pacific oyster contains 18.9 mg zinc, or 172% daily value for adults.
Intimately involved in immune responses
When it comes to improving immune health, many people think zinc immediately. Although zinc does not “work” alone, it is indeed vital for supporting virtually every stage of an immune response when our bodies encounter pathogens (e.g., virus and bacteria) or dangers (e.g., tissue damage caused by oxidative stress or toxins). For example:2,3

• Zinc helps maintain integrity of the physical and biochemical barriers such as skin and mucus membranes (mucosal cells) in the respiratory and gastrointestinal tract to block entry of pathogens.
• Zinc supports differentiation and proliferation of innate immune cells and enhances their functioning, such as monocyte phagocytic capacity and natural killer cell cytotoxic activity.
• Zinc has antioxidant properties that protect against reactive oxygen species (ROS).
• Zinc is important for the development and activation of T lymphocytes supporting adaptive immune responses.
• Zinc is involved in production of the antibody IgG.
• Zinc supports production of antimicrobial substances such as interferon gamma (IFNγ) that deter growth of microbes.

Deficiency negatively impacting health
The recommended dietary allowance (RDA) for men is 11mg/day and women is 8mg/day.4 Unfortunately, dietary intake of zinc in the US has been inadequate. Older adults, vegetarians, and people with chronic inflammatory conditions or renal disease are especially at risk of deficiency.5,6 Zinc deficiency has been linked to impaired immune functions, and its clinical impact can be detrimental, such as increased susceptibility to infections including viral infections of respiratory tract, increased diarrhea and pneumonia, impaired wound healing, and increased risk of inflammatory and autoimmune disorders.7-10

Modulation of NLRP3 inflammasome activity
Importantly, zinc has been shown to be involved in modulation of NLRP3 inflammasome activation, as well. Inflammasomes—of which there are several types, and the NLRP3 inflammasome is considered the most clinically relevant—are protein complexes in the cell that can sense signals from pathogens or dangers.11  Activation of inflammasomes is part of the innate immune defenses that leads to amplification of downstream inflammatory and immune responses. However, inflammasome activation is a double-edge sword; activations that are not well-regulated have been linked to not only tissue collateral damage during infections, but also immune and metabolic disorders such as autoimmune disease, type 2 diabetes, atherosclerosis, and even Alzheimer’s disease.12
Figure: NLRP3 inflammasome activation

It has been demonstrated that zinc depletion in immune cells activates the NLRP3 inflammasome, induces secretion of the proinflammatory cytokine IL-1β, and contributes to inflammation.13 Fortunately, deficiency in zinc can be corrected by eating foods rich in zinc or via supplementation of zinc. In a cell model of an inflammatory condition, zinc treatment inhibited NLRP3 inflammasome activation. It was achieved via activation of the Nrf2 antioxidant pathway and reduced production of reactive oxygen species.14
Supplementation markedly improving various health outcomes
There is strong clinical evidence demonstrating the benefits of zinc supplementation on immune health. Here are only some of the examples:

• Zinc supplementation at 30 mg/day for 3 months effectively increased serum zinc concentration in elderly (65 y/o or older living in nursing home), which improved T cell proliferation.15
• Zinc supplementation at 45 mg/day for 1 year significantly reduced the incidence of infection, levels of inflammatory cytokines, and markers of oxidative stress in elderly subjects.16
• In a meta-analysis involving common cold patients, zinc (as lozenges) use led to reduction in common cold duration by nearly 3 days.17
• Zinc supplementation reduced the incidence of otitis media (inflammation of the middle ear caused by infection) in young children without causing serious adverse events.18
• A meta-analysis demonstrated that zinc supplementation significantly reduced the frequency and severity of diarrhea and respiratory tract infections in children.19

Summary
There is very strong evidence supporting the role of zinc in immune functions, but the benefits of zinc go beyond supporting immune health. Many studies have demonstrated the role of zinc in the management of type 2 diabetes,20 age-related macular degeneration,21 depression,22 and more. Therefore, it is important to maintain adequate dietary intakes of zinc. So next time you see oysters in a restaurant (after measures of social distancing have been lifted, or course), be sure to thank them. Or better yet, eat them!
Citations

1. Charifi M et al. The sense of hearing in the Pacific oyster, Magallana gigas. PLoS One. 2017;12:e0185353.
2. Gombart AF et al. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients. 2020;12:pii. E236.
3. Wessels I et al. Zinc as a gatekeeper of immune function. Nutrients. 2017;9:pii. E1286.
4. Gibson RS et al. A review of dietary zinc recommendations. Food Nutr Bull. 2016;37:443-460.
5. Prasad AS. Discovery of human zinc deficiency: 50 years later. J Trace Elem Med Biol. 2012;26:66-69.
6. International Zinc Nutrition Consultative Group. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull. 2004;25:S99-203.
7. Prentice S. They are what you eat: can nutritional factors during gestation and early infancy modulate the neonatal immune response? Front Immunol. 2017;8:1641.
8. Maywald M et al. Zinc signals and immunity. Int J Mol Sci. 2017;18:2222.
9. Savino W et al. Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses. Proc Nutr Soc. 2010;69:636-643.
10. Sanna A et al. Zinc status and autoimmunity: a systematic review and meta-analysis. Nutrients. 2018;10:pii:E68.
11. Abderrazak A et al. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015;4:296-307.
12. Yang Y et al. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10:128.
13. Summersgill H et al. Zinc depletion regulates the processing and secretion of IL-1beta. Cell Death Dis. 2014;5:e1040.
14. Fan Y et al. Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells. Mol Med Rep. 2017;16:5195-5202.
15. Barnett JB et al. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2016;103:942-951.
16. Prasad AS 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.
17. Hemila H et al. Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis. Br J Clin Pharmacol. 2016;82:1393-1398.
18. Gulani A et al. Zinc supplements for preventing otitis media. Cochrane Database Syst Rev. 2014:CD006639.
19. Aggarwal R et al. Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: a meta-analysis. Pediatrics. 2007;119:1120-1130.
20. Wang X et al. Zinc supplementation improves glycemic control for diabetes prevention and management: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2019;110:76-90.
21. Evans JR et al. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2017;7:CD000254.
22. Swardfager W et al. Zinc in depression: a meta-analysis. Biol Psychiatry. 2013;74:872-878.

Lewis Chang, PhD is Scientific Editorial Manager of R&D at Metagenics. Dr. Chang received his PhD in Nutritional Sciences at University of Washington, along with his MS in Nutrition and Public Health from Teachers College, Columbia University and BS in Pharmacy from National Taiwan University. Prior to joining Metagenics, he conducted dissertation research and completed a research assistantship and postdoctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, WA. Dr. Chang has authored or co-authored and managed the publication of over 30 peer-reviewed journal articles and numerous scientific abstracts and posters. He has quite a green thumb, enjoys opera, theater and jazz, and loves cooking, collecting art, and learning to play gypsy jazz guitar.

by Cassie Story, RDN

Abstract: Although it was not identified and isolated until the 1930s, vitamin C has been known to protect against and treat certain disease states since the 18th century. Ask any health care practitioner to recall the first nutrient deficiency they learned about, and vitamin C will likely top the list. Images of sailors in the 1700s returning to shore with bleeding gums, fatigue, and even death due to a deficiency in this potent, water-soluble, antioxidant micronutrient likely come to mind. Ask any consumers what nutrient they should take during cold and flu season to help minimize their risk of infection, and once again, vitamin C will typically be their reply. For these reasons, vitamin C is arguably one of the most famous micronutrients. This post will dive into the role of vitamin C within the body and the potential health benefits of optimal intake and review considerations for its impact on the immune and respiratory systems.

Function of vitamin C in the body
Unlike most animals, due to the result of random genetic mutations, humans have lost the ability to synthesize ascorbate in our livers, making vitamin C an essential micronutrient.1 This important antioxidant serves many functions in disease prevention and optimal health status. Vitamin C is involved in protein metabolism and is required for the biosynthesis of certain neurotransmitters, as well as L-carnitine and collagen. It also serves as a cofactor for several enzyme reactions.2 Mild insufficiency, or hypovitaminosis C, has been associated with low mood, and more severe deficiency can lead to the clinical syndrome of scurvy, a condition that remains diagnosed in individuals today—and has played a role in global public health outbreaks.3,4

As vitamin C is a regenerative antioxidant, research continues to evaluate the impact of vitamin C and its role in reducing the destructive effect of free radicals. This may assist in the prevention of or delay in certain cancers, cardiovascular disease, and other conditions where oxidative stress affects human health.5 Not only does vitamin C have biosynthetic and antioxidant functions, it plays an important role in immune function and assists in the absorption of nonheme iron.

Vitamin C absorption and status
Vitamin C concentrations are tightly controlled within the body. Despite this, studies indicate that hypovitaminosis C and deficiency exist worldwide. Hypovitaminosis C is prevalent within certain populations in developed countries, including individuals with obesity, those who smoke, and people with low fruit and vegetable intake—and is the fourth leading micronutrient deficiency in the United States.6

Dietary intake is a primary factor in an individual’s vitamin C status. The amount consumed and frequency of consumption correlate well with plasma status and deficiency risk.6 Well absorbed in small quantities (i.e.: 200-400 mg at a time), through sodium-dependent vitamin C transporter-1 (SVCT-1), the enterocyte is rapidly saturated, and vitamin C is then transported, at varying concentrations, to several body tissues.7 Many organs have concentration-dependent mechanisms to retain vitamin C during situations where supply is low, namely brain tissue and adrenal glands.8

Plasma saturation occurs at a concentration between 70-80 µmol/L, although typical laboratory assessment methods prove highly susceptible to inaccuracies—leaving it challenging for many clinicians to assess accurate vitamin C status in their patients.8

​Factors that impact vitamin C status6

Recommended intake and sources  
Population-based studies indicate that a majority of Americans meet the recommended dietary allowance (RDA), which is 90 milligrams (mg) per day for males and 75 mg per day for females, although ideal intake and serum concentrations have been a topic of debate for health experts around the world, and recommended values are not universal.9 A range of identified health benefits have been observed at higher intake levels. This has led a number of international agencies to increase their dietary recommendations, as the previous recommendations were based on the low level needed to prevent scurvy, which is estimated to be 10 mg per day.9

Despite its popularity among health care professionals and consumers, average US adult intakes are estimated to be 105 mg for males and 84 mg for females.10 While it is apparent that most individuals meet the RDA, many do not achieve the estimated optimal intake needed for its positive biological impact—which is speculated to be much higher, with many experts suggesting a daily intake of 200 mg for optimal health.11

Food sources
Fresh fruit and vegetables are the main contributors of dietary vitamin C, with fruit intake correlating strongly with plasma vitamin C levels.6 Major contributors of vitamin C in the typical American diet are potatoes, citrus fruit, and tomatoes. Foods rich in vitamin C include oranges, kiwi, berries, papayas, mangos, melons, spinach, asparagus, and Brussels sprouts.12

Impact of vitamin C supplementation

​Supplemental use 
Five or more servings of fruits and vegetables per day can often lead to an optimal daily vitamin C intake of 200 mg, with special attention to one or two servings coming from a high-vitamin C source. This is not always possible, and taking supplements—in addition to dietary intake, can help to achieve and maintain optimal status.

• Large, population-based health surveys in the US (NHANES) and Canada (CHMS) found that vitamin C status was at least 20 µmol/L higher in supplement users, with negligible deficiency rates (0-2%), compared to nonusers.13,14
• Studies from the UK indicate that individuals who had lower socioeconomic status and took no dietary supplements had a two-fold odds ratio of having a lower vitamin C status (< 28 µmol/L), compared to those with higher socioeconomic status and some supplement use.15

Exposure to environmental toxins, including air pollution and tobacco smoke, is associated with lower vitamin C status in both non-smoking adults and children.

• Supplemental vitamin C (along with other antioxidants such as vitamin E and beta-carotene) has been found to decrease oxidative biomarkers in individuals who are exposed to tobacco smoke.6

​Dietary supplement sources
The majority of dietary supplements provide vitamin C in the form of ascorbic acid, which has an equivalent bioavailability to the naturally occurring ascorbic acid found in food sources.16 Other forms of supplemental vitamin C include mineral ascorbates, liposomal-encapsulated, or combination products. The upper limit has been set at 2,000 mg per day, due to the potential of diarrhea or other gastrointestinal (GI) effects, not due to a potential toxic impact.
Buffered forms have been shown to help prevent GI distress and offer higher absorption than traditional ascorbic acid, possibly related to the presence of other minerals and amino acids. One study on 22 healthy subjects found that a buffered form of vitamin C improved absorption in healthy individuals by 18-25% when compared to ascorbic acid.17

Immune, inflammation, and respiratory impact
Vitamin C appears to play a role in both prevention and treatment of respiratory and systemic infections by boosting several immune cell functions.18 Vitamin C status may be depleted by various disease states due to inflammatory processes and greater oxidative stress. During times of active infection, requirements for vitamin C increase with the severity of the infection—which requires significantly higher intakes to reach normal plasma status to make up for the added metabolic demands.6 Prophylactic prevention, on the other hand, advises that dietary intake is, at minimum, adequate. However, in order to achieve plasma saturation and optimize cell and tissue levels, doses of 100-200 mg per day are suggested.18
​
The role of vitamin C in immune defense and inflammation is multifactorial. It plays a role in inflammatory mediators by modulating cytokine production, decreasing histamine levels, and offering protection of key immune enzymes. Apoptosis, the necessary programmed cellular death of neutrophils, supports the resolution of inflammation and helps to prevent extreme tissue damage. Caspases are oxidant-sensitive, thiol-dependent, key enzymes in the apoptotic process. Vitamin C is thought to protect the caspase-dependent apoptotic process following the activation of neutrophils. Numerous studies have found weakened neutrophil apoptosis in patients with severe infection when compared to control groups. Animal studies have shown that administration of vitamin C greatly reduced the numbers of neutrophils in the lungs of septic animals.18

Cytokines, cell-signaling molecules secreted by certain immune cells, respond to infection and inflammation and can elicit a pro- or anti-inflammatory response. Vitamin C has been found to regulate systemic and leukocyte-derived cytokines in a multifaceted way. Preclinical, in vitro and animal studies have shown both positive and unfavorable effects of incubation with vitamin C. The effect of vitamin C seems to depend on the cell type and/or the inflammatory stimulant but overall appears to assist in normalizing cytokine generation.18

Following chemical exposure, natural killer (NK) cell function, as well as T and B cell function, decreases and can remain low for several weeks to months.17 Studies have shown enhanced immune function and improvement in NK cell function after oral doses of buffered vitamin C, as well as T and B cell function improvement following toxic chemical exposure. One study, of 55 subjects, used individualized dosing (60 mg/kg of body weight) of buffered vitamin C to evaluate the impact of high-dose vitamin C following a toxic chemical exposure and found that functional immune abnormalities can be restored following such an event.19

Allergies and the common cold
Histamine, an immune mediator, is produced in response to pathogens and stress. Vitamin C depletion is associated with higher circulating levels of histamine. Intervention studies with supplemental oral vitamin C (range 125 mg–2 g/day) have found a decrease in histamine levels; however, they have been more impactful in patients with allergic symptoms compared to infectious diseases.18
The impact of vitamin C intake on common cold incidence has been an area of interest for the last 50 years.20 Meta-analyses have indicated that supplementation with 200 mg or more per day is effective in reducing the severity and duration of the common cold, and in individuals who have inadequate vitamin C status, vitamin C supplementation may decrease the incidence of the common cold. Thus, it appears that taking high-dose supplemental vitamin C daily during cold and flu season may reduce the risk of cold duration and severity.21

Respiratory impact
Exposure to air pollution oxidants and tobacco smoke can alter the oxidant-antioxidant balance in the body and lead to oxidative stress.22 When vitamin C levels are insufficient, antioxidant defenses are impaired and can further compound the impact of oxidative stress within the body. Environmental oxidants can damage the respiratory tract lining fluid and increase the risk of respiratory disease. Vitamin C acts as a free-radical scavenger that can scavenge superoxide radicals and oxidant air pollutants—and its antioxidant properties offer protection to lung cells exposed to oxidants caused by various pollutants, heavy metals, pesticides, and xenobiotics.23
Vitamin C also plays a role in proper endothelial function, and deficiency has been associated in pulmonary arterial hypertension.24 Patients with acute respiratory infections have been found to have low plasma levels of vitamin C, and supplementation has been found to return plasma levels to normal and decrease the severity of respiratory symptoms. Beneficial effects of vitamin C supplementation on recovery of respiratory infections, including pneumonia, have been identified. Studies on hospitalized patients with pneumonia have found that supplemental vitamin C at a low dose (250-800 mg/day) reduced length of stay by 19% compared to those without vitamin C supplementation. Those that were given higher doses (500 mg–1.6 g per day) had an even greater reduction at 36%.18 It appears that low vitamin C levels seen during respiratory infections are both a source and a result of the disease.

Respiratory health case study10
In a recent case study, a man in his 60s experienced shortness of breath and swelling of the legs associated with a frank vitamin C deficiency, which was attributed to a diet low in vitamin C and no supplemental intake. He was treated with supplemental vitamin C at 1,000 mg twice daily; his symptoms resolved after five months on this treatment plan.

• Of note, his plasma ascorbic acid upon presentation was .1 mg/dL (normal range: .4-2.0 mg/dL), which increased to 1.5 mg/dL by the end of the treatment.

​Genetic variants 
Recent discoveries in genetic variants’ influence on vitamin C status have been found. Several single-nucleotide variants have been identified in the SLC23A1 gene, which encodes SVCT-1 and is responsible for the active uptake of dietary vitamin C and the reuptake of filtered vitamin C in the kidneys. In vitro data for this variant indicates a 40-75% decrease in vitamin C absorption from the gut and has been shown to present in 6-16% in those of African descent.25
A common variant of the hemoglobin-binding protein haptoglobin (Hp2-2) influences the metabolism of vitamin C. In vitro studies have found that this alters the ability to bind to hemoglobin and leads to an increase in oxidation of vitamin C.26 The Hp2-2 variant seems to have a greater impact on individuals with dietary intakes of less than 90 mg of vitamin C per day.27
Individuals with genetic variants that influence vitamin C status may require even higher dietary intakes. Luckily, high-dose vitamin supplementation has been found to amend certain gene-variant defects.28

Conclusion
A majority of individuals would benefit from increasing fruit and vegetable intake to improve overall nutrition status, including vitamin C. Ensuring adequate intake of vitamin C through diet and with the use of supplementation is important for proper immune function and resistance to infections. This is especially critical for individuals with certain genetic SNPs or other lifestyle factors that may lead to a decline in vitamin C status.

Citations

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11. Low Dog, Tieraona. Fortify Your Life. Washington, D.C., National Geographic Society, 2016.
12. S. Department of Agriculture, Agricultural Research Service. FoodData Central (www.fdc.nal.usda.gov). Accessed December 16, 2020..
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19. Heuser G et al. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-c. Immunpharm and Immunotox. 1997;19(3):291-312.
20. Douglas RM et al. Vitamin C for preventing and treating the common cold. PLoS Med. 2005;2:e168.
21. Hemila H. The role of vitamin C in the treatment of the common cold. Am Fam Physician. 2007;76:1111-1115.
22. Romieu I et al. Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J. 2008;31:179-196.
23. Haryanto B et al. Multivitamin supplementation supports immune function and ameliorates conditions triggered by reduced air quality. Vitam Miner. 2015;4:1-15.
24. Gayen SK et al. Vitamin C deficiency-induced pulmonary arterial hypertension. CHEST. 2020;157(2):e21-e23.
25. Michels AJ et al. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu Rev Nutr. 2013;33:45-70.
26. Delanghe JR et al. Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clin Chem. 2007;53:1397-1400.
27. Cahill LE et al. Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid. J Nutrigenet Nutrigenom. 2009;2:292-301.
28. Ames BN et al. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity. Am J Clin Nutr. 2009;90:1121-1123.

Cassie I. Story is a Registered Dietitian Nutritionist with 17 years of experience in treating metabolic and bariatric surgery and medical weight loss patients. She spent the first decade of her career as the lead dietitian for a large volume clinic in Scottsdale, Arizona. For the past seven years, she has been working with industry partners in order to improve nutrition education within the field. She is a national speaker, published author, and enjoys spending time with her two daughters hiking and creating new recipes in the kitchen!