The Great Pumpkin is Not Just for Decoration

pumpkinsMany of us associate pumpkin with autumn, especially Thanksgiving. That’s a shame because there’s a wealth of goodness in that winter squash, and it deserves more than mere seasonal entertainment. It’s low in calories and fat, and provides vitamins, minerals, fiber, and phytochemicals essential to a healthy diet. A cup has only 83 calories and one gram of fat, which is just enough to allow its use in recipes that call for shortening or oil. Measure for measure, you can use canned pumpkin puree for half the fat in a cake or cookie recipe. Some people even add it to their morning oatmeal with cinnamon and a little, like a teaspoon, of brown sugar. Here we’re talking about the nutritive value of canned pumpkin, which is denser than what you would get from spending a few hours trying to hatchet out and distill the flesh from a fresh pumpkin.  The only virtue realized from a fresh squash is the potential to roast the seeds for a snack later on… if you have the composure to separate the seeds from the stringy fibers in the core.

The Color of Vitamin A
Because of its color, pumpkin is immediately identified as being a source of beta-carotene, the precursor to vitamin A that has no measurable level of liver burden. Beta-carotene is a molecule that the body easily changes to vitamin A in the intestine, and is found in plants, as opposed to pre-formed vitamin A common to animal products, as from butter and eggs. This fat-soluble vitamin is known to fight infections, to help treat skin disorders, to improve night vision and to ameliorate dry eyes, all the while performing anti-oxidant functions. Although beta-carotene does not, pre-formed vitamin A can lead to orange skin and yellow eyes, a state that disappears when levels are adjusted or intake is temporarily discontinued. The bioavailability of beta-carotene—the proportion that can be absorbed, transported and utilized by the body—is influenced by a few factors: supplemental beta-carotene is better absorbed that that from foods; food processing and cooking can enhance availability; the presence of fat in the gut aids absorption (only about three grams per meal is needed).

One cup of pumpkin yields more than 500 milligrams of potassium, an essential mineral in which most North Americans are shallow, often getting much less than the RDI of 4700 milligrams. In the body, potassium helps to keep blood pressure under control (Barri, 1997) (Hajjar, 2001) (Geleijnse, 1996), may help to encourage positive bone mineral density (New, 1997, 2000) (Tucker, 1999), and may reduce risk of stroke (Ascherio, 1998) (Fang, 2000) (Bazzano, 2001). Epidemiological evidence indicates that potassium intake and blood pressure are inversely correlated, with the greatest hypotensive effect found in those with the highest blood pressure. Inclusion of potassium in the management of hypertension was suggested in the late 90’s (Barri, 1997).  Knowing your potassium intake might be more important than you think.

Another of the vision-friendly carotenoids in pumpkin is lutein, a pigment for which spinach has been lauded. Concentrated in the macula, the part of the retina responsible for central vision, lutein rescues the eye from oxidative stressors and the high-energy photons of blue light that are known to increase risk for macular degeneration (Richer, 2004). Naturally combined with its isomer, zeaxanthin (the yellow pigment also in corn, saffron and paprika), lutein may also lower the risk of cataracts (Barker, 2010) (Moeller, 2008) (SanGiovanni, 2007).

Hypoglycemic Activity of Pumpkin
Though the foregoing is reason enough to eat pumpkin more often than once a year, another virtue was made public earlier in this century. China has received some bad publicity in the recent past, with melamine in baby formula, toxic bean sprouts and contaminated pet foods, but its scientific community looks less toward dollar signs and more toward humanitarian ventures. While examining the medicinal properties of plants, pharmaceutical researchers in Shanghai found pumpkin to be among the species that exhibit hypoglycemic activity. Specific polysaccharides in pumpkin and a few other plants apparently are able to restore the function of pancreatic cells and cause an increase in insulin output by the functional beta cells. Scientists noticed that lower dosages of anti-diabetes drugs were needed when the plant compounds were concomitantly administered. Frequency of drug administration and its unwelcome side effects were also reduced (Jia, 2003). As with many natural approaches to the management of disease, dose makes the difference. Later study in Beijing found that 1000 mg/kg doses of protein-bound pumpkin polysaccharide were considerably more effective than half that amount (Quanhong, 2005).

Much of what we all learn as students is based on prior knowledge, using it as a springboard for additional investigation. One of the active pumpkin factors that eventually “sprang from the board” and found to be most effective in lowering glucose is trigonelline (TRG), an alkaloid also appearing in coffee, sea urchins and jellyfish, the latter two not being suggested as complementary to the pie. A derivative of vitamin B6, trigonelline is believed also to have anti-migraine, antiseptic, and anti-carcinogenic properties. If roasted at temperatures greater than 230° C (446° F), this alkaloid yields nicotinic acid—niacin. Experimental use of TRG attenuated triglycerides as well as serum glucose in laboratory animals bred to mimic human disorders (Yoshinari, 2009).  Anti-oxidant status is severely compromised in diabetes, causing an increase in damage by free radicals. TRG was seen to ameliorate oxidative stress and to return related blood markers to near normal levels (Zhou, 2011, 2012).

The Gentle Giant
You’d think that, as big as they can get, pumpkins are rough and tough. They’re actually very tender, starting with seeds that don’t do well in cold soil and seedlings that succumb to frost. If planted too early, they often rot before you’re ready to pick them.  What is truly surprising about pumpkins’ cultivation is that they fare poorly if fertilized with the typical N-P-K fertilizers used in the garden. To ascertain initial results, researchers duplicated experiments five more times in order to remove doubts that high fertilizer rates decrease anti-oxidant concentrations in the fruits (Oloyede, Apr 2012 and May 2012).

Preparing fresh pumpkin is more work than fun unless you do it once a year, and just for the novelty of it. Uncut pumpkins can be stored for weeks in a well-ventilated space, but once you cut ‘em you got to use ‘em. Canned keeps seemingly forever. Fruit, leaves, flowers and seeds are edible. But we think of the flesh in pies, pancakes, muffins, custards, soups, soufflés, and yes, even ravioli. Now you can eat for health as well as flavor.


Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD.
The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22.
Arch Ophthalmol. 2007 Sep;125(9):1225-32.

Ascherio A, Rimm EB, Hernán MA, Giovannucci EL, Kawachi I, Stampfer MJ, Willett WC.
Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men.
Circulation. 1998 Sep 22;98(12):1198-204.

Bakuradze T, Lang R, Hofmann T, Stiebitz H, Bytof G, Lantz I, Baum M, Eisenbrand G, Janzowski C.
Antioxidant effectiveness of coffee extracts and selected constituents in cell-free systems and human colon cell lines.
Mol Nutr Food Res. 2010 Dec;54(12):1734-43.

Barker FM 2nd.
Dietary supplementation: effects on visual performance and occurrence of AMD and cataracts.
Curr Med Res Opin. 2010 Aug;26(8):2011-23.

Barri YM, Wingo CS.
The effects of potassium depletion and supplementation on blood pressure: a clinical review.
Am J Med Sci. 1997 Jul;314(1):37-40.

Bazzano LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L, Whelton PK
Dietary potassium intake and risk of stroke in US men and women: National Health and Nutrition Examination Survey I epidemiologic follow-up study.
Stroke. 2001 Jul;32(7):1473-80.

Czok G.
Coffee and health
Z Ernahrungswiss. 1977 Dec;16(4):248-55.

Fang J, Madhavan S, Alderman MH.
Dietary potassium intake and stroke mortality.
Stroke. 2000 Jul;31(7):1532-7.

Geleijnse JM, Witteman JC, den Breeijen JH, Hofman A, de Jong PT, Pols HA, Grobbee DE.
Dietary electrolyte intake and blood pressure in older subjects: the Rotterdam Study.
J Hypertens. 1996 Jun;14(6):737-41.

Hajjar IM, Grim CE, George V, Kotchen TA
Impact of diet on blood pressure and age-related changes in blood pressure in the US population: analysis of NHANES III.
Arch Intern Med. 2001 Feb 26;161(4):589-93.

Huang XE, Hirose K, Wakai K, Matsuo K, Ito H, Xiang J, Takezaki T, Tajima K.
Comparison of lifestyle risk factors by family history for gastric, breast, lung and colorectal cancer.
Asian Pac J Cancer Prev. 2004 Oct-Dec;5(4):419-27.

Jia W, Gao W, Tang L.
Antidiabetic herbal drugs officially approved in China.
Phytother Res. 2003 Dec;17(10):1127-34.

Jian L, Du CJ, Lee AH, Binns CW.
Do dietary lycopene and other carotenoids protect against prostate cancer?
Int J Cancer. 2005 Mar 1;113(6):1010-4.

Jiang Z, Du Q.
Glucose-lowering activity of novel tetrasaccharide glyceroglycolipids from the fruits of Cucurbita moschata.
Bioorg Med Chem Lett. 2011 Feb 1;21(3):1001-3. Epub 2010 Dec 10.

Mishkinsky J, Joseph B, Sulman FG.
Hypoglycaemic effect of trigonelline.
Lancet. 1967 Dec 16;2(7529):1311-2.

Moeller SM, Voland R, Tinker L, Blodi BA, Klein ML, Gehrs KM, Johnson EJ, Snodderly DM, Wallace RB, Chappell RJ, Parekh N, Ritenbaugh C, Mares JA; CAREDS Study Group; Women’s Helath Initiative.
Collaborators (88)
Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women’s Health Initiative.
Arch Ophthalmol. 2008 Mar;126(3):354-64.

Mohamed Makni, Mediha Sefi, Hamadi Fetoui, El Mouldi Garoui, Nabil K. Gargouri, Tahia Boudawar, Najiba Zeghala
Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats
Food and Chemical Toxicology. Vol 48, Iss 8–9, Aug–Sept 2010, Pp 2407–2412

New SA, Bolton-Smith C, Grubb DA, Reid DM.
Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women.
Am J Clin Nutr. 1997 Jun;65(6):1831-9.

New SA, Robins SP, Campbell MK, Martin JC, Garton MJ, Bolton-Smith C, Grubb DA, Lee SJ, Reid DM.
Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health?
Am J Clin Nutr. 2000 Jan;71(1):142-51.

Oloyede FM, Agbaje GO, Obuotor EM, Obisesan IO.
Nutritional and antioxidant profiles of pumpkin (Cucurbita pepo Linn.) immature and mature fruits as influenced by NPK fertilizer.
Food Chem. 2012 Nov 15;135(2):460-3. Epub 2012 Apr 30.

Oloyede FM, Obisesan IO, Agbaje GO, Obuotor EM.
Effect of NPK fertilizer on chemical composition of pumpkin (Cucurbita pepo Linn.) seeds.
ScientificWorldJournal. 2012;2012:808196. Epub 2012 May 2.

Quanhong L, Caili F, Yukui R, Guanghui H, Tongyi C.
Effects of protein-bound polysaccharide isolated from pumpkin on insulin in diabetic rats.
Plant Foods Hum Nutr. 2005 Mar;60(1):13-6.

Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J.
Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial).
Optometry. 2004 Apr;75(4):216-30.

Suzuki K, Ito Y, Nakamura S, Ochiai J, Aoki K.
Relationship between serum carotenoids and hyperglycemia: a population-based cross-sectional study.
J Epidemiol. 2002 Sep;12(5):357-66.

Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP.
Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women.
Am J Clin Nutr. 1999 Apr;69(4):727-36.

van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM.
Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.
Diabetes Care. 2009 Jun;32(6):1023-5. Epub 2009 Mar 26.

Carolina Médici Veronezi, Neuza Jorge
Bioactive Compounds in Lipid Fractions of Pumpkin (Cucurbita sp) Seeds for Use in Food
Journal of Food Science. Volume 77, Issue 6, pages C653–C657, June 2012

Yoshinari O, Sato H, Igarashi K.
Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.
Biosci Biotechnol Biochem. 2009 May;73(5):1033-41. Epub 2009 May 7.

Zhou J, Zhou S, Zeng S.
Experimental diabetes treated with trigonelline: effect on β cell and pancreatic oxidative parameters
Fundam Clin Pharmacol. 2011 Dec 16. doi: 10.1111/j.1472-8206.2011.01022.x. [Epub ahead of print]

Zhou J, Chan L, Zhou S.
Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.
Curr Med Chem. 2012 Jul 1;19(21):3523-31.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Supplement Actions & Interactions

spoon-full-of-vitaminsThe potential for vitamin toxicity is real. Most Americans believe that vitamins and other supplements are safe. That’s true if they are used correctly. Too many people still think that if one is good, ten is better. Especially alarming is the scenario in which a well-meaning mother tells her youngster to chew his daily animal-shaped gummy vitamin because it’s good for him and will make him grow to be big and strong, like Daddy.  Junior doesn’t know that ten is not better, climbs up to the counter, struggles to open the bottle, and eats a handful of vitamins. If the vitamins are made from food the worry is minor, but still there. If synthetic, like most, the danger for an adverse reaction is much greater and becomes a medical emergency.  Fat-soluble vitamins have a higher potential for poisoning because they can accumulate in the body, but there is comfort knowing that, even with more than 71,000 vitamin overdose reports to poison control centers in 2010, no one ever died from a vitamin excess (Bronstein, 2011). The actual number is 71,545 out of 2,784,907, representing about 2.5% of all exposures. The medical community that reviewed total toxic exposures ruled vitamins to be safe.

Antioxidants: Vitamin A
Vitamin A is a group of fat-soluble substances called retinoids, including retinol, retinal, retinoic acid and retinyl esters that are involved in immunity, vision, reproduction, and cellular communication. As an essential component of rhodopsin, vitamin A is critical for vision. Since it supports healthy cell growth and division, it is likewise important to the heart, lungs, kidneys, and other organs. This nutrient exists in two forms. Pre-formed vitamin A is called retinol, found mostly in animal foods and converted to the metabolically active forms known as retinal and retinoic acid. The other form of vitamin A is the provitamin carotenoid, beta-carotene, although other carotenes exist as alpha-carotene and beta-cryptoxanthin, all of which are converted to vitamin A and metabolized to retinal and retinoic acid. All forms of the vitamin are made into micelles and are absorbed by the duodenum. In a cascade of metabolic events, retinol is converted to retinal and then to retinoic acid. Much of the vitamin A from food comes as retinol. About one third of the dietary source comes from plants, especially grains, oils, and green and yellow fruits and vegetables, such as carrots and pumpkin.

Because the liver maintains vitamin A levels within a narrow window, overdose is possible by overzealous supplementation, and can be serious in children. But that does not exempt adults from the hazard. Intake of much more than 1.5 milligrams of supplemental A each day (5000 IU), particularly of preformed vitamin A, can backfire and reduce bone mineral density by as much as 10% in the femur and 6% for the total body, thereby increasing risk for hip fractures (Melhus, 1998). But vitamin A precursors are not totally exculpated (Feskanich, 2002). Observational studies on retinol conclude that total vitamin A intake is more important than the source, whether from supplements or from foods, and that twice the current RDA (3000 IU or 900 mcg for adults) is enough to compromise bone integrity (Crandall, 2004). The Brazilians noted an increase in risk of skeletal fractures when intake of dietary vitamin A from retinol was excessive, as bone resorption was stimulated and bone formation inhibited (Genaro, 2004).

Nutrition Labels Have a Purpose
Good intentions are insufficient to ward off the throes of taking too much of a supplement, whether alone or as part of a multi-vitamin or other complex. This is why you need to read labels of all the supplement bottles you open. If each bottle contains a little bit of the same nutrient, you need to add the numbers to arrive at the value you swallow, lest you take too much and possibly suffer harm. Water-soluble nutrients are not usually the problem; fat-soluble ones are. High doses of vitamin A over long periods of time, regardless of source, can antagonize vitamin K and reduce its effectiveness as a clotting agent and cause internal hemorrhage (Grubbs, 1985). Most people don’t monitor vitamin K intake from supplements. Neither do they watch how many green leafy vegetables they eat to account for vitamin K supply. Except for that prescribed by a medical doctor, high doses of vitamin A means taking more than twice the daily recommendation.

Deficiencies of nutrients often parallel one another. Low zinc levels limit the bioavailability of vitamin A, regardless of how much is ingested (Rahman, 2992).  Iron deficiency is a known cause of anemia. In the absence of ample vitamin A stores, even supplemental iron is inhibited despite its enhanced hematological response by vitamin C (Fishman, 2000). Certain foods can inhibit or facilitate supplemental nutrient uptake and absorption, too. In the presence of fiber, vitamin A absorption is enhanced (Kasper, 1979).

Vitamin A and Your Liver
Because vitamin A is handled by the liver, anything that burdens that organ might contribute to problems down the line. Acetaminophen is notorious for causing liver damage, even fatalities, and  amiodarone, carbamazepine, methotrexate, and a slew of other drugs can cause liver concerns in the presence of excess vitamin A. Taking 25,000 IU of vitamin A daily for several months will turn your eyes and skin yellow and, for a pregnant, woman, can cause birth defects (Hathcock, 1990). Mixing vitamin A, often prescribed for acne, with tetracycline antibiotic prescribed for the same condition can cause intracranial hypertension with resultant headaches, nausea and vomiting, as well as pulsate tinnitus and vision symptoms (Walters, 1981). Heaven forbid you take an Rx blood thinner and overdo the vitamin A at levels greater than 10,000 IU a day.  Vitamin K will be antagonized and hemorrhage becomes a possibility (Hardman, 1996).

When it comes to fat-soluble vitamins, be careful not to overdo it. Although toxicity is relatively rare, is it especially possible in the elderly, chronic alcohol users and those with a genetic predisposition to high cholesterol (Russell, 2000). Avoid taking more than the RDA of pre-formed vitamin A (retinol) during pregnancy, being alert to fortification of food and counting it as part of daily intake. Synthetic derivatives, such as those used to treat skin conditions (Accutane, Retin-A) either orally or topically are no less dangerous merely because they come from a pharmacist. The terms “acetate” and “palmitate” describe preformed vitamin A. Although beta-carotene is safer, use common sense.


Alvin C. Bronstein, MD ; Daniel A. Spyker, MD, PhD ; Louis R. Cantilena, Jr, MD, PhD, et al
2010 Annual Report of the American Association of Poison Control Centers ’ National Poison Data System (NPDS): 28th Annual Report
Clinical Toxicology (2011), 49, 910–941

Crandall C.
Vitamin A intake and osteoporosis: a clinical review.
J Womens Health (Larchmt). 2004 Oct;13(8):939-53.

Feskanich D, Singh V, Willett WC, Colditz GA.
Vitamin A intake and hip fractures among postmenopausal women.
JAMA. 2002 Jan 2;287(1):47-54.

Fishman SM, Christian P, West KP.
The role of vitamins in the prevention and control of anaemia.
Public Health Nutr. 2000 Jun;3(2):125-50.

Genaro Pde S, Martini LA.
Vitamin A supplementation and risk of skeletal fracture.
Nutr Rev. 2004 Feb;62(2):65-7.

Grubbs CJ, Hill DL, Farnell DR, Kalin JR, McDonough KC.
Effect of long-term administration of retinoids on rats exposed transplacentally to ethylnitrosourea.
Anticancer Res. 1985 Mar-Apr;5(2):205-9.
Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman’s The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.

Hathcock JN.
Metabolic mechanisms of drug-nutrient interactions.
Fed Proc. 1985 Jan;44(1 Pt 1):124-9.

Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundaresan PR, Wilkening VL.
Evaluation of vitamin A toxicity.
Am J Clin Nutr. 1990 Aug;52(2):183-202.

Kasper H, Rabast U, Fassl H, Fehle F.
The effect of dietary fiber on the postprandial serum vitamin A concentration in man.
Am J Clin Nutr. 1979 Sep;32(9):1847-9.

Melhus H, Michaëlsson K, Kindmark A, Bergström R, Holmberg L, Mallmin H, Wolk A, Ljunghall S.
Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.
Ann Intern Med. 1998 Nov 15;129(10):770-8.

Michaëlsson K, Lithell H, Vessby B, Melhus H.
Serum retinol levels and the risk of fracture.
N Engl J Med. 2003 Jan 23;348(4):287-94.

Allen LH, Peerson JM; Maternal Micronutrient Supplementation Study Group Collaborators (37)
Impact of multiple micronutrient versus iron-folic acid supplements on maternal anemia and micronutrient status in pregnancy.
Food Nutr Bull. 2009 Dec;30(4 Suppl):S527-32

Rahman MM, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO.
Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children.
Am J Clin Nutr. 2002 Jan;75(1):92-8.

Russell RM.
The vitamin A spectrum: from deficiency to toxicity
Am J Clin Nutr. 2000 Apr;71(4):878-84.

Vetrugno M, Maino A, Cardia G, Quaranta GM, Cardia L.
A randomised, double masked, clinical trial of high dose vitamin A and vitamin E supplementation after photorefractive keratectomy.
Br J Ophthalmol. 2001 May;85(5):537-9.

Walters BN, Gubbay SS.
Tetracycline and benign intracranial hypertension: report of five cases.
Br Med J (Clin Res Ed). 1981 Jan 3;282(6257):19-20.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Get Something Free… Radicals The Saga of Vitamins A, C and E

vitamins-foodThe same oxygen you need to stay alive and to burn food for energy makes you oxidize just as fast as a rusty fender on the old jalopy in the back yard…or maybe in the driveway if your surname is Clampett at 90210. If your apples turn brown and your fish or butter becomes rancid, blame it on oxygen. Lungs, eyes, skin, fruits, vegetables, herbs, you name it. If it has cells, it’ll oxidize and those cells will change. But it’s a normal part of living. Fret not. The Creator gave us a way to intercept the free radicals and undo their dastardly deeds. These molecules are “free” because they have parts missing, and they scour the neighborhood looking for replacements, sort of like the original equipment manufacturer you look for when rebuilding your ’57 Chevy. Being on a mission, these molecules will rampage to hook up with another molecule and steal electrons. Frankly, it would be simpler if free radicals just killed a cell and left it at that. But nope, it has to start the dominoes falling. If a cell were bumped off, the body would make a new one. Instead, the cell’s DNA gets damaged enough to set the stage for disaster.

Broken DNA can make a cell mutate and set up a chain reaction for other cells to do the same thing. Not good. Free radicals damage a bunch of cells. Overexposure to the sun, cigarette smoke (either first-hand or second-hand), vehicle exhaust (diesel is the worst), comestibles that are called food but really are not, booze, heavy metals and a few other hazards can work over time to create chronic sickness, including cancer, heart disease, Alzheimer’s disease and Parkinson’s. How do we fix things? Maybe it’s easier to put the brakes on oxidation in the first place. Waddya think?

Antioxidants are molecules that work to prevent damage due to both normal body processes and exposure to some chemicals and environmental perils. One of the benefits of antioxidants is their ability to slow oxidation in the smallest parts of the body—proteins and DNA. There are antioxidants made by the body and those that come from food or supplements. The water-soluble ones react with oxidants in the blood and in the free spaces inside cells. The fat-soluble protect cell membranes from a process known as lipid peroxidation. Some body tissues might have more of one antioxidant than another. For example, one may be plentiful in the kidney, but almost absent from the heart, while the opposite might apply to a different antioxidant. Some may appear at the same concentration in every part of the body.

The body has its own antioxidant defense system, one that relies partly on minerals for proper functioning. Superoxide dismutase (SOD) needs copper, zinc and manganese; glutathione peroxidase needs selenium; and catalase depends on iron. Except for selenium, minerals are not defined as antioxidants, but as cofactors in their manufacture. Although this endogenous system demands respect, we’re going to focus on the most commonly used exogenous antioxidants—vitamins A, C, and E. In most activities, biochemical as well as psycho-social, the buck stops somewhere. With antioxidants, the buck stops at glutathione, so we’ll give that molecule the respect it merits, particularly for the work it does in the lungs (Rahman, 2006) (Nadeem, 2008).

Vitamin A is a general term for a group of related fat-soluble substances, including retinal and retinol, cited as preformed vitamin A. Retinal is converted to retinoic acid, the form that influences gene transcription. Beta-carotene and other carotenoids are referred to as provitamin A compounds. Beta-carotene, the carotenoid that comes from yellow and orange foods, is converted by the liver to retinol. Some forms of this vitamin are occasionally used in pharmacological doses to treat a few conditions, including retinitis pigmentosa (Berson, 1993), acute promyelocytic leukemia (Thurnam, 1999) (Ross, 1999), and various skin conditions (Ross, 1999). However, it’s important to realize that high doses of retinoids, especially if synthetic, can override the body’s own control mechanisms and present toxicities.

Preformed vitamin A is available as retinyl palmitate or acetate, overdose of which is easy to happen because people don’t read labels and often get the vitamin from more than one source, such as from a multi-vitamin or fortified food and later from a separate supplement.  The chief concern is that vitamin A is rapidly taken up, but slowly cleared from the body. Alcohol depletes vitamin A stores from the liver, but taking vitamin A while drinking is an accident waiting to happen. Keeping intake from a supplement at 2500 IU (750 mcg) should do the trick, while avoiding adverse effects on bone in the geriatric crowd. Getting vitamin A from foods is not normally a problem of overdose unless the food is fortified with it (Promislow, 2002). Beta-carotene, by the way, has about half the potency of preformed A, where 2 mcg of supplemental beta-carotene can be converted to 1 mcg of retinol. With foods, though, it takes 12 mcg to make 1 mcg of retinol. Can you see why it’s hard to overdose on cantaloupe?  Pumpkin, carrots, sweet potatoes, mangoes and collards are decent sources.

Water-soluble vitamin C is ascorbic acid, not citric acid, the latter made commercially by the fermentation of molasses. Even though citric acid can be found in oranges, there aren’t enough oranges on the planet to meet a fraction of the demand from the food industry.  Besides being an antioxidant, vitamin C is required for the synthesis of collagen, the structural element that holds us together. Additionally, it helps to make the neurotransmitter norepinephrine. Most animals can make the vitamin C they need; humans and guinea pigs cannot (Linster, 2007). Like all reducing agents, vitamin C itself becomes oxidized. Such an entity donates one or more electrons to a substance that already has become oxidized and is a free radical. In this instance, an antioxidant can become a damaging molecule, running around, looking for an electron to replace the one it just donated. But there is a rescue molecule, where the buck stops, as mentioned earlier. Too much ascorbic acid may cause kidney stones, since oxalates are metabolites of vitamin C, but doses up to 2000 mg a day shouldn’t be a concern for healthy people (Taylor, 2004) (Auer, 1998). The original RDA was barely enough to prevent scurvy, the reason for the RDA in the first place. Citrus, bell peppers, broccoli, potatoes, tomatoes, and strawberries are good sources.

Vitamin E is a fat-soluble family of eight antioxidants—four tocopherols and four tocotrienols. Any adverse publicity you read about vitamin E is based only on alpha-tocopherol, synthetically produced at that and administered to people with pre-existing conditions. The alpha- form of tocopherol is the one most often encountered because it’s actively maintained in the body and has the greatest nutritional significance, although the beat-, delta-, and gamma- forms have merit. It is an antioxidant that prevents the oxidation of fats (rancidity). This is especially important to the cell membrane. After vitamin E gives up an electron, it becomes a free radical itself, but vitamin C and A sacrifice themselves for its salvation. Besides being antioxidant, vitamin E appears to modulate some genes, to inhibit cell proliferation, and to control platelet aggregation and monocyte adhesion. It might even interact with enzymes, structural proteins and lipids (Zingg, 2004) (Ricciarelli, 2002), and regulate cell signaling (Rimbach, 2002). The body recognizes synthetic forms of vitamin E as sham, so it pays to find the d- form, not the dl-form. Oils, avocados and nuts are good sources. If there be a caveat, it is that too much can interfere with blood clotting. Therefore, if taking an anti-coagulant medication, check with the doctor before supplementing. If a tooth extraction or more serious surgery is in the offing, stop supplementation days ahead of time.

Once an antioxidant gives up an electron it can act like the thugs it’s trying to sequester. It needs its own savior. Here comes glutathione to the rescue. This is the body’s master antioxidant, made from amino acids.  As long as sulfur-containing amino acid stores are adequate and are regularly refilled through diet or supplementation (N-acetyl cysteine is such a source), glutathione is able to spare an electron here and there to replace the ones lost by vitamins A, C and E. The dysregulation of glutathione is known to be a prime factor in pathology, from diabetes to pulmonary fibrosis (Lu, 2009), so it pays to consume enough sulfur foods to get the methionine, taurine and cysteine that glutathione needs to keep itself in perfect form. The crucifers, onions and garlic, and animal products, including egg yolks, are substantial sources.

Having the best home run hitter in the league doesn’t guarantee a championship season. You need defense, too; you need a team. The same applies to antioxidants. The overall collection rather than the heavily advertised super antioxidant is what it takes because different antioxidants counteract damage by different types of free radicals within different cellular compartments. Natural and balanced is the rule.


Abdullah Acar, M. Ugur Cevik, Osman Evliyaoglu, Ertugrul Uzar, Yusuf Tamam, Adalet Arıkanoglu, et al
Evaluation of serum oxidant/antioxidant balance in multiple sclerosis
Acta Neurologica Belgica. September 2012, Volume 112, Issue 3, pp 275-280

Auer BL, Auer D, Rodgers AL.
The effect of ascorbic acid ingestion on the biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation.
Clin Chem Lab Med. 1998 Mar;36(3):143-7.

Mehmet Balci, Erdinc Devrim and Ilker Durak
Effects of Mobile Phones on Oxidant/Antioxidant Balance in Cornea and Lens of Rats
Current Eye Research.2007, Vol. 32, No. 1 , Pages 21-25

Berr C, Richard MJ, Gourlet V, Garrel C, Favier A.
Enzymatic antioxidant balance and cognitive decline in aging–the EVA study.
Eur J Epidemiol. 2004;19(2):133-8.

Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W.
A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa.
Arch Ophthalmol. 1993 Jun;111(6):761-72.

Hassan Boskabadi, Mahdieh Moeini, Fatemeh Tara, Shima Tavallaie, Hamidreza Saber, Raheleh Nejati, Golkoo Hosseini, Hesam Mostafavi-Toroghi, Gordon A. A. Ferns, Majid Ghayour-Mobarhan
Determination of Prooxidant–Antioxidant Balance during Uncomplicated Pregnancy Using a Rapid Assay
Journal of Medical Biochemistry.June 2013. Volume 32, Issue 3, Pages 227–232

Cristóvão, C.; Cristóvão, L.; Nogueira, F.; Bicho, M.
Evaluation of the oxidant and antioxidant balance in the pathogenesis of chronic obstructive pulmonary disease
Revista Portuguesa de Pneumologia. 2013;19:70-5.

Dringen R
Metabolism and functions of glutathione in brain.
Prog Neurobiol. 2000 Dec;62(6):649-71.

Firuzi O, Miri R, Tavakkoli M, Saso L.
Antioxidant therapy: current status and future prospects.
Linster CL, Van Schaftingen E.

Curr Med Chem. 2011;18(25):3871-88.
Vitamin C. Biosynthesis, recycling and degradation in mammals.
FEBS J. 2007 Jan;274(1):1-22.

Lu SC.
Regulation of glutathione synthesis.
Mol Aspects Med. 2009 Feb-Apr;30(1-2):42-59.

Lu SC.
Glutathione synthesis.
Biochim Biophys Acta. 2013 May;1830(5):3143-53.

Celestyna Mila-Kierzenkowska, Alina Woźniaka, Tomasz Boraczyński, Michał Szpinda,  Bartosz Woźniak, Alicja Jurecka, Anna Szpinda
Thermal stress and oxidant–antioxidant balance in experienced and novice winter swimmers
J of Thermal Biology. Volume 37, Issue 8, December 2012, Pages 595–601

Nadeem A, Masood A, Siddiqui N.
Oxidant–antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options.
Ther Adv Respir Dis. 2008 Aug;2(4):215-35.

Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E.
Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study.
J Bone Miner Res. 2002 Aug;17(8):1349-58.

Rahman I, Biswas SK, Kode A.
Oxidant and antioxidant balance in the airways and airway diseases.
Eur J Pharmacol. 2006 Mar 8;533(1-3):222-39.

Ricciarelli R, Zingg JM, Azzi A.
The 80th anniversary of vitamin E: beyond its antioxidant properties.
Biol Chem. 2002 Mar-Apr;383(3-4):457-65.

Rimbach G, Minihane AM, Majewicz J, Fischer A, Pallauf J, Virgli F, Weinberg PD.
Regulation of cell signalling by vitamin E.
Proc Nutr Soc. 2002 Nov;61(4):415-25.

Ross AC. Vitamin A and retinoids. In: Shils M, Olson JA, Shike M, Ross AC. ed. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999:305-327.

Amirhossein Sahebk, Akram Mohammadi, Ali Atabati, Shamim Rahiman, Shima Tavallaie Mehrdad Iranshahi, Saeed Akhlaghi, Gordon AA Ferns, Majid Ghayour-Mobarhan
Curcuminoids Modulate Pro-Oxidant–Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals
Phytother. Res. Article first published online: 15 MAR 2013. doi: 10.1002/ptr.4952

Taylor EN, Stampfer MJ, Curhan GC.
Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up.
J Am Soc Nephrol. 2004 Dec;15(12):3225-32.

Thurnham DI, Northrop-Clewes CA.
Optimal nutrition: vitamin A and the carotenoids.
Proc Nutr Soc. 1999 May;58(2):449-57.

Zingg JM, Azzi A.
Non-antioxidant activities of vitamin E.
Curr Med Chem. 2004 May;11(9):1113-33.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.