- The Grapefruit Diet
- Table 1. Nutritional Value of Grapefruit
- Grapefruit and Weight Loss
- Grapefruit juice and certain Medicines May Not Mix
- Eating whole fruits linked to lower risk of type 2 diabetes
- Grapefruit and Vitamin C
- What are some of the Benefits of Vitamin C on Health
- Vitamin C and Cancer Prevention
- Vitamin C and Cancer Treatment
The Grapefruit Diet
Grapefruit is a citrus fruit. Grapefruit is a source of vitamin C, fiber, potassium, pectin, and other nutrients. Some components might have antioxidant effects that might help protect cells from damage or reduce cholesterol. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit.
People use the fruit, oil from the peel, and extracts from the seed as medicine. Grapefruit seed extract is processed from grapefruit seeds and pulp obtained as a byproduct from grapefruit juice production. Vegetable glycerin is added to the final product to reduce acidity and bitterness.
Grapefruit juice is used for high cholesterol, “hardening of the arteries” (atherosclerosis), cancer, a skin disease called psoriasis, and for weight loss and obesity. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.
In an study involving 72 hypercholesterolemic patients, ages 43-71 years who have had a coronary bypass surgery were divided into 3 groups. Groups 1 and 2, were given 100 ml and 200 ml fresh grapefruit juice, whilst group 3 was the control. After 30 consecutive days of fresh grapefruit juice supplemented diets, improvements in serum lipids levels were found in Group 1 and Group 2 versus control group (no changes in the CG were found). The researchers concluded that Diet supplemented with this juice positively influences serum lipid, albumin, and fibrinogen levels and their antioxidant capacities. Addition of fresh grapefruit juice to generally accepted diets may be beneficial for hypercholesterolemic patients 1). What is lacking from this study was the unknown substances in the grapefruit that affect the cholesterol and the antioxidants.
Grapefruit seed extract is taken by mouth for bacterial, viral, and fungal infections including yeast infections.
Grapefruit oil is applied to the skin for muscle fatigue, hair growth, toning the skin, and for acne and oily skin. It is also used for the common cold and flu (influenza). It is not clear how the oil might work for medicinal uses.
Table 1. Nutritional Value of Grapefruit
Value per 100 g
cup sections, with juice 230 g
large (approx 4-1/2″ dia) 166 g
medium (approx 4″ dia) 128 g
small (approx 3-1/2″ dia) 100 g
|Total lipid (fat)||g||0.10||0.23||0.17||0.13||0.10|
|Carbohydrate, by difference||g||8.08||18.58||13.41||10.34||8.08|
|Fiber, total dietary||g||1.1||2.5||1.8||1.4||1.1|
|Vitamin C, total ascorbic acid||mg||34.4||79.1||57.1||44.0||34.4|
|Vitamin A, RAE||µg||46||106||76||59||46|
|Vitamin A, IU||IU||927||2132||1539||1187||927|
|Vitamin E (alpha-tocopherol)||mg||0.13||0.30||0.22||0.17||0.13|
|Vitamin D (D2 + D3)||µg||0.0||0.0||0.0||0.0||0.0|
|Vitamin K (phylloquinone)||µg||0.0||0.0||0.0||0.0||0.0|
|Fatty acids, total saturated||g||0.014||0.032||0.023||0.018||0.014|
|Fatty acids, total monounsaturated||g||0.013||0.030||0.022||0.017||0.013|
|Fatty acids, total polyunsaturated||g||0.024||0.055||0.040||0.031||0.024|
|Fatty acids, total trans||g||0.000||0.000||0.000||0.000||0.000|
Grapefruit and Weight Loss
The grapefruit diet has outlasted most fad diets. People were even trying it back in the 1930s. Its fans claim that grapefruit contains certain enzymes that, when eaten before other foods, help burn off fat. However, more evidence is needed to rate the effectiveness of eating fresh grapefruit daily increases weight loss in overweight people.
Grapefruit doesn’t burn fat and if you’re hoping that grapefruit will melt fat, you’re going to be disappointed. Remember the cabbage soup diet ? The detox diet ? How about the Hollywood 48 Hour Miracle diet, the Subway diet, the apple cider vinegar diet, the HCG diet and a host of forgettable celebrity diets ?
The truth is, almost any diet will work if it helps you take in fewer calories. Diets do this in four main ways:
- Getting you to eat certain “good” foods and/or avoid “bad” ones.
- Cutting calories. Swapping high-calorie foods for lower calorie alternatives and reducing portion sizes.
- Changing how you behave and the ways you think or feel about food.
- Getting to become physically active. Every weight-loss program should include physical activity. Exercise plus calorie restriction can help give your weight loss a boost. Exercise also offers numerous health benefits, including improving your mood, strengthening your cardiovascular system and reducing your risk of heart disease and type 2 diabetes. And exercise is an important factor in maintaining weight loss. People who get regular physical activity may be more likely to maintain their weight loss.
The best diet for losing weight is one that is good for all parts of your body, from your brain to your gut and not just for your waistline and wallet. It is also one you can live with for a long time. In other words, a diet that offers plenty of good tasting and healthy choices, banishes few foods, and doesn’t require an extensive and expensive list of groceries or supplements.
Successful weight loss requires permanent changes to your eating habits and physical activity. This means you need to find a weight-loss approach that you can embrace for life. Even then, you’ll likely always have to remain vigilant about your weight. But combining a healthier diet with more activity is the best way to lose weight and keep it off for the long term.
The classic version of the grapefruit diet meal plan involves:
- Most versions of the grapefruit diet recommend eating it with every meal.
- Cutting back on sugar and carbs (including rice, potatoes, and pasta)
- Avoiding certain foods, such as celery and white onion
- Eating more of foods that are high in protein, fat, and/or cholesterol (such as eggs, pork, and red meat)
- Eating grapefruit or grapefruit juice before or with every meal
- Most variations also cut calories, some to as low as 800 calories per day.
- On the diet, you also drink 8 glasses of water and 1 cup of coffee daily.
Don’t bother with this diet. Such a limited variety of foods in small portions is the prescription for boredom. It’s exactly the formula to cause most dieters to give up trying to lose weight.
Grapefruit can be part of a healthy weight loss diet because it’s nutritious, not because of any mysterious fat-burning properties. If you’re a grapefruit lover, reap the benefits of this super-nutritious fruit by enjoying a serving before meals. A half grapefruit or a glass of grapefruit juice before meals may help fill you up, so you’ll eat fewer calories at meals and potentially lose weight.
Grapefruit juice and certain Medicines May Not Mix
Grapefruit and grapefruit juice are healthful, providing enough vitamin C, potassium, dietary fiber, and other nutrients to earn the American Heart Association’s “heart-check” mark. That’s the good news. The bad news is that grapefruit juice can interact with dozens of medications, sometimes dangerously.
Grapefruit juice and fresh grapefruit can interfere with the action of some prescription drugs, as well as a few non-prescription drugs. This interaction can be dangerous according to the Food and Drug Administration’s Office of Clinical Pharmacology 3). With most drugs that interact with grapefruit juice, the grapefruit juice increases the absorption of the drug into the bloodstream. When there is a higher concentration of a drug, you tend to have more adverse events.
Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4 in the small intestine 4). Certain substances in grapefruit juice block the action of CYP3A4, so instead of being metabolized, more of the drug enters the bloodstream and stays in the body longer. The result: potentially dangerous levels of the drug in your body 5).
The amount of the CYP3A4 enzyme in the intestine varies from one person to another. Some people have a lot, and others have just a little—so grapefruit juice may affect people differently when they take the same drug.
While scientists have known for several decades that grapefruit juice can cause a potentially toxic level of certain drugs in the body, more recent studies have found that the grapefruit juice has the opposite effect on a few other drugs.
Drinking grapefruit juice several hours before or several hours after you take your medicine may still be dangerous, so it’s best to avoid or limit consuming grapefruit juice or fresh grapefruit when taking certain drugs 6).
Examples of some types of drugs that grapefruit juice can interact with are:
- some statin drugs to lower cholesterol, such as Zocor (simvastatin), Lipitor (atorvastatin) and Pravachol (pravastatin)
- some blood pressure-lowering drugs, such as Nifediac and Afeditab (both nifedipine)
- some organ transplant rejection drugs, such as Sandimmune and Neoral (both cyclosporine)
- some anti-anxiety drugs, such as BuSpar (buspirone)
- some anti-arrhythmia drugs, such as Cordarone and Nexterone (both amiodarone)
- some antihistamines, such as Allegra (fexofenadine)
Grapefruit juice does not affect all the drugs in the categories above. Ask your pharmacist or other health care professional to find out if your specific drug is affected.
There is a well-characterized interaction between grapefruit juice and certain statins (drugs that can lower blood cholesterol). This interaction leads to the effective dose of a statin being increased, with resulting benefits in reducing LDL cholesterol and coronary heart disease. The risk of rhabdomyolysis (side effects of statin drugs causing the breakdown of muscle cells) is much less in comparison, and overall, there is no need to advise people on statins to avoid drinking grapefruit juice 7).
Eating more whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, according to a new study led by Harvard School of Public Health researchers 8). Greater consumption of fruit juices was associated with a higher risk of type 2 diabetes. The study is the first to look at the effects of individual fruits on diabetes risk.
The researchers’ findings provided a novel evidence suggesting that certain fruits (blueberries, grapes, and apples) may be especially beneficial for lowering diabetes risk.
The researchers examined data gathered between 1984 and 2008 from 187,382 participants in three long-running studies (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study). Participants who reported a diagnosis of diabetes, cardiovascular disease, or cancer at enrollment were excluded. Results showed that 12,198 participants (6.5%) developed diabetes during the study period.
The researchers looked at overall fruit consumption, as well as consumption of individual fruits: grapes or raisins; peaches, plums, or apricots; prunes; bananas; cantaloupe; apples or pears; oranges; grapefruit; strawberries; and blueberries. They also looked at consumption of apple, orange, grapefruit, and “other” fruit juices.
People who ate at least two servings each week of certain whole fruits — particularly blueberries, grapes, and apples — reduced their risk for type 2 diabetes by as much as 23% in comparison to those who ate less than one serving per month. Conversely, those who consumed one or more servings of fruit juice each day increased their risk of developing type 2 diabetes by as much as 21%. The researchers found that swapping three servings of juice per week for whole fruits would result in a 7% reduction in diabetes risk.
The fruits’ glycemic index (a measure of how rapidly carbohydrates in a food boost blood sugar) did not prove to be a significant factor in determining a fruit’s association with type 2 diabetes risk. However, the high glycemic index of fruit juice — which passes through the digestive system more rapidly than fiber-rich fruit — may explain the positive link between juice consumption and increased diabetes risk.
The researchers theorize that the beneficial effects of certain individual fruits could be the result of a particular component. Previous studies have linked anthocyanins found in berries and grapes to lowered heart attack risk, for example. But more research is necessary to determine which components in the more beneficial fruits influence diabetes risk.
The researchers further endorsed current recommendations on increasing whole fruits consumption, but not fruit juice, as a measure for diabetes prevention 9).
Grapefruit and Vitamin C
Grapefruit juice can be part of a healthful diet—most of the time. It has vitamin C and potassium—substances your body needs to work properly. Vitamin C, also known as L-ascorbic acid or ascorbate, is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement. Vitamin C is synthesized from D-glucose or D-galactose by many plants and animals. However, humans lack the enzyme L-gulonolactone oxidase required for ascorbic acid synthesis and must obtain vitamin C through food or supplements 10), 11). In the body, it acts as an antioxidant, helping to protect cells from the damage caused by free radicals. Free radicals are compounds formed when our bodies convert the food we eat into energy. People are also exposed to free radicals in the environment from cigarette smoke, air pollution, and ultraviolet light from the sun.
Vitamin C plays a role in collagen, carnitine, hormone, and amino acid formation. It is essential for wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports immune function, and facilitates the absorption of iron 12). High-Dose vitamin C, when taken by intravenous (IV) infusion, vitamin C can reach much higher levels in the blood than when it is taken by mouth. Studies suggest that these higher levels of vitamin C may cause the death of cancer cells in the laboratory. Surveys of healthcare practitioners at United States complementary and alternative medicine conferences in recent years have shown that high-dose IV vitamin C is frequently given to patients as a treatment for infections, fatigue, and cancers, including breast cancer 13).
Vitamin C is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters; vitamin C is also involved in protein metabolism 14), 15). Collagen is an essential component of connective tissue, which plays a vital role in wound healing. Vitamin C is also an important physiological antioxidant 16) and has been shown to regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E) 17). Ongoing research is examining whether vitamin C, by limiting the damaging effects of free radicals through its antioxidant activity, might help prevent or delay the development of certain cancers, cardiovascular disease, and other diseases in which oxidative stress plays a causal role. In addition to its biosynthetic and antioxidant functions, vitamin C plays an important role in immune function 18) and improves the absorption of nonheme iron 19), the form of iron present in plant-based foods. Insufficient vitamin C intake causes scurvy, which is characterized by fatigue or lassitude, widespread connective tissue weakness, and capillary fragility 20), 21), 22), 23), 24), 25), 26).
What are some of the Benefits of Vitamin C on Health
Due to its function as an antioxidant and its role in immune function, vitamin C has been promoted as a means to help prevent and/or treat numerous health conditions. Scientists are studying vitamin C to understand how it affects health. Here are several examples of what this research has shown.
Vitamin C and Cancer Prevention
Epidemiologic evidence suggests that people with high intakes of vitamin C from fruits and vegetables might have a lower risk of getting many types of cancer, such as lung, breast, and colon cancer, perhaps, in part, due to their high vitamin C content 27), 28). Vitamin C can limit the formation of carcinogens, such as nitrosamines 29), 30), in vivo; modulate immune response 31), 32); and through its antioxidant function, possibly attenuate oxidative damage that can lead to cancer 33).
Most case-control studies have found an inverse association between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus 34), 35). Plasma concentrations of vitamin C are also lower in people with cancer than controls 36).
However, evidence from prospective cohort studies is inconsistent, possibly due to varying intakes of vitamin C among studies. In a cohort of 82,234 women aged 33–60 years from the Nurses’ Health Study, consumption of an average of 205 mg/day of vitamin C from food (highest quintile of intake) compared with an average of 70 mg/day (lowest quintile of intake) was associated with a 63% lower risk of breast cancer among premenopausal women with a family history of breast cancer 37). Conversely, Kushi and colleagues did not observe a significantly lower risk of breast cancer among postmenopausal women consuming at least 198 mg/day (highest quintile of intake) of vitamin C from food compared with those consuming less than 87 mg/day (lowest quintile of intake) 38). A review by Carr and Frei concluded that in the majority of prospective cohort studies not reporting a significantly lower cancer risk, most participants had relatively high vitamin C intakes, with intakes higher than 86 mg/day in the lowest quintiles 39). Studies reporting significantly lower cancer risk found these associations in individuals with vitamin C intakes of at least 80–110 mg/day, a range associated with close to vitamin C tissue saturation 40), 41), 42).
Evidence from most randomized clinical trials suggests that vitamin C supplementation, usually in combination with other micronutrients, does not affect cancer risk. In the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study, a randomized, double-blind, placebo-controlled clinical trial,13,017 healthy French adults received antioxidant supplementation with 120 mg ascorbic acid, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, and 20 mg zinc, or placebo 43). After a median follow-up time of 7.5 years, antioxidant supplementation lowered total cancer incidence in men, but not in women. In addition, baseline antioxidant status was related to cancer risk in men, but not in women 44). Supplements of 500 mg/day vitamin C plus 400 IU vitamin E every other day for a mean follow-up period of 8 years failed to reduce the risk of prostate or total cancer compared with placebo in middle-aged and older men participating in the Physicians’ Health Study II 45). Similar findings were reported in women participating in the Women’s Antioxidant Cardiovascular Study 46). Compared with placebo, supplementation with vitamin C (500 mg/day) for an average of 9.4 years had no significant effect on total cancer incidence or cancer mortality. In a large intervention trial conducted in Linxian, China, daily supplements of vitamin C (120 mg) plus molybdenum (30 mcg) for 5–6 years did not significantly affect the risk of developing esophageal or gastric cancer 47). Moreover, during 10 years of follow-up, this supplementation regimen failed to significantly affect total morbidity or mortality from esophageal, gastric, or other cancers 48). A 2008 review of vitamin C and other antioxidant supplements for the prevention of gastrointestinal cancers found no convincing evidence that vitamin C (or beta-carotene, vitamin A, or vitamin E) prevents gastrointestinal cancers 49). A similar review by Coulter and colleagues found that vitamin C supplementation, in combination with vitamin E, had no significant effect on death risk due to cancer in healthy individuals 50).
At this time, the evidence is inconsistent on whether dietary vitamin C intake affects cancer risk. Results from most clinical trials suggest that modest vitamin C supplementation alone or with other nutrients offers no benefit in the prevention of cancer.
A substantial limitation in interpreting many of these studies is that investigators did not measure vitamin C concentrations before or after supplementation. Plasma and tissue concentrations of vitamin C are tightly controlled in humans. At daily intakes of 100 mg or higher, cells appear to be saturated and at intakes of at least 200 mg, plasma concentrations increase only marginally 51), 52), 53), 54), 55). If subjects’ vitamin C levels were already close to saturation at study entry, supplementation would be expected to have made little or no difference on measured outcomes 56), 57), 58), 59).
Vitamin C and Cancer Treatment
More than fifty years ago, a study suggested that cancer was a disease of changes in connective tissue caused by a lack of vitamin C. In the 1970’s, it was proposed that high-dose ascorbic acid could help build resistance to disease or infection and possibly treat cancer 60).
During the 1970s, studies by Cameron, Campbell, and Pauling suggested that high-dose vitamin C has beneficial effects on quality of life and survival time in patients with terminal cancer 61), 62). However, some subsequent studies—including a randomized, double-blind, placebo-controlled clinical trial by Moertel and colleagues at the Mayo Clinic 63) did not support these findings. In the Moertel study, patients with advanced colorectal cancer who received 10 g/day vitamin C fared no better than those receiving a placebo. The authors of a 2003 review assessing the effects of vitamin C in patients with advanced cancer concluded that vitamin C confers no significant mortality benefit 64).
Emerging research suggests that the route of vitamin C administration (intravenous vs. oral) could explain the conflicting findings 65), 66), 67). Most intervention trials, including the one conducted by Moertel and colleagues, used only oral administration, whereas Cameron and colleagues used a combination of oral and intravenous (IV) administration. Oral administration of vitamin C, even of very large doses, can raise plasma vitamin C concentrations to a maximum of only 220 micromol/L, whereas IV administration can produce plasma concentrations as high as 26,000 micromol/L [46,47]. Concentrations of this magnitude are selectively cytotoxic to tumor cells in vitro 68), 69). Research in mice suggests that pharmacologic doses of IV vitamin C might show promise in treating otherwise difficult-to-treat tumors 70). A high concentration of vitamin C may act as a pro-oxidant and generate hydrogen peroxide that has selective toxicity toward cancer cells 71), 72), 73). Based on these findings and a few case reports of patients with advanced cancers who had remarkably long survival times following administration of high-dose IV vitamin C, some researchers support reassessment of the use of high-dose IV vitamin C as a drug to treat cancer 74), 75), 76), 77), 78). Surveys of healthcare practitioners at United States complementary and alternative medicine conferences in recent years have shown that high-dose IV vitamin C is frequently given to patients as a treatment for infections, fatigue, and cancers, including breast cancer 79).
It is uncertain whether supplemental vitamin C and other antioxidants might interact with chemotherapy and/or radiation 80). Therefore, individuals undergoing these procedures should consult with their oncologist prior to taking vitamin C or other antioxidant supplements, especially in high doses 81), 82).
References [ + ]
|1.||↵||J Agric Food Chem. 2004 Aug 11;52(16):5215-22.Fresh israeli jaffa sweetie juice consumption improves lipid metabolism and increases antioxidant capacity in hypercholesterolemic patients suffering from coronary artery disease: studies in vitro and in humans and positive changes in albumin and fibrinogen fractions. https://www.ncbi.nlm.nih.gov/pubmed/15291499/|
|2.||↵||United States Department of Agriculture, Agriculture Research Service. USDA Food Composition Databases. https://ndb.nal.usda.gov/ndb/|
|3, 4, 5, 6.||↵||U.S. Food and Drug Administration. Grapefruit Juice and Medicine May Not Mix. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm292276.htm|
|7.||↵||The American Journal of Medicine January 2016, Volume 129, Issue 1, Pages 26–29 . Grapefruit Juice and Statins. http://www.amjmed.com/article/S0002-9343(15)00774-3/fulltext|
|8, 9.||↵||Harvard University, Harvard School of Public Health. Eating whole fruits linked to lower risk of type 2 diabetes. https://www.hsph.harvard.edu/news/press-releases/eating-whole-fruits-linked-to-lower-risk-of-type-2-diabetes/|
|10.||↵||Naidu KA: Vitamin C in human health and disease is still a mystery? An overview. Nutr J 2: 7, 2003. https://www.ncbi.nlm.nih.gov/pubmed/14498993?dopt=Abstract|
|11, 14, 20, 27, 33, 65, 68.||↵||Li Y, Schellhorn HE. New developments and novel therapeutic perspectives for vitamin C. J Nutr 2007;137:2171-84. https://www.ncbi.nlm.nih.gov/pubmed/17884994?dopt=Abstract|
|12.||↵||Merck Sharp & Dohme Corp., Merck Manual. Vitamin C (Ascorbic Acid). https://www.merckmanuals.com/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/vitamin-c|
|13, 79.||↵||National Cancer Institute. High-Dose Vitamin C–Patient Version. https://www.cancer.gov/about-cancer/treatment/cam/patient/vitamin-c-pdq#link/_5|
|15, 21, 28, 29, 31, 34, 36, 39, 40, 51.||↵||Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999;69:1086-107. https://www.ncbi.nlm.nih.gov/pubmed/10357726?dopt=Abstract|
|16.||↵||Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377-81. Ascorbate is an outstanding antioxidant in human blood plasma. https://www.ncbi.nlm.nih.gov/pubmed/2762330%20?dopt=Abstract|
|17, 18, 22, 32, 35.||↵||Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002;5:66-74. https://www.ncbi.nlm.nih.gov/pubmed/12134712?dopt=Abstract|
|19.||↵||Gershoff SN. Vitamin C (ascorbic acid): new roles, new requirements? Nutr Rev 1993;51:313-26. https://www.ncbi.nlm.nih.gov/pubmed/8108031?dopt=Abstract|
|23.||↵||Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. Pediatrics 2001;108:E55. https://www.ncbi.nlm.nih.gov/pubmed/11533373?dopt=Abstract|
|24.||↵||Wang AH, Still C. Old world meets modern: a case report of scurvy. Nutr Clin Pract 2007;22:445-8. https://www.ncbi.nlm.nih.gov/pubmed/17644699?dopt=Abstract|
|25.||↵||Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. https://www.nap.edu/catalog/9810/dietary-reference-intakes-for-vitamin-c-vitamin-e-selenium-and-carotenoids|
|26.||↵||Stephen R, Utecht T. Scurvy identified in the emergency department: a case report. J Emerg Med 2001;21:235-7. https://www.ncbi.nlm.nih.gov/pubmed/11604276?dopt=Abstract|
|30.||↵||Hecht SS. Approaches to cancer prevention based on an understanding of N-nitrosamine carcinogenesis. Proc Soc Exp Biol Med 1997;216:181-91. https://www.ncbi.nlm.nih.gov/pubmed/9349687?dopt=Abstract|
|37.||↵||Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 1999;91:547-56. https://www.ncbi.nlm.nih.gov/pubmed/10088626?dopt=Abstract|
|38, 54.||↵||Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women’s Health Study. Am J Epidemiol 1996;144:165-74. https://www.ncbi.nlm.nih.gov/pubmed/8678048?dopt=Abstract|
|41, 53, 56.||↵||Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 1996;93:3704-9. https://www.ncbi.nlm.nih.gov/pubmed/8623000?dopt=Abstract|
|42.||↵||Levine M, Wang Y, Padayatty SJ, Morrow J. A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci U S A 2001;98:9842-6. https://www.ncbi.nlm.nih.gov/pubmed/11504949?dopt=Abstract|
|43.||↵||Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 2004;164:2335-42. https://www.ncbi.nlm.nih.gov/pubmed/15557412?dopt=Abstract|
|44.||↵||Galan P, Briançon S, Favier A, Bertrais S, Preziosi P, Faure H, et al. Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels? Br J Nutr 2005;94:125-32. https://www.ncbi.nlm.nih.gov/pubmed/16115341?dopt=Abstract|
|45.||↵||Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2009;301:52-62. https://www.ncbi.nlm.nih.gov/pubmed/19066368?dopt=Abstract|
|46.||↵||Lin J, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst 2009;101:14-23. https://www.ncbi.nlm.nih.gov/pubmed/19116389%20?dopt=Abstract|
|47.||↵||Taylor PR, Li B, Dawsey SM, Li JY, Yang CS, Guo W, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res 1994;54(7 Suppl):2029s-31s. https://www.ncbi.nlm.nih.gov/pubmed/8137333?dopt=Abstract|
|48.||↵||Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, et al. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst 2009;101:507-18. https://www.ncbi.nlm.nih.gov/pubmed/19318634?dopt=Abstract|
|49.||↵||Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 2008;(3):CD004183. https://www.ncbi.nlm.nih.gov/pubmed/18677777?dopt=Abstract|
|50, 64.||↵||Coulter I, Hardy M, Shekelle P, Udani J, Spar M, Oda K, et al. Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer. Evidence Report/Technology Assessment Number 75. AHRQ Publication No. 04-E003. Rockville, MD: Agency for Healthcare Research and Quality, 2003. https://www.ncbi.nlm.nih.gov/pubmed/15523748?dopt=Abstract|
|52.||↵||Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 2004;140:533-7. https://www.ncbi.nlm.nih.gov/pubmed/15068981?dopt=Abstract|
|55.||↵||Taylor PR, Li B, Dawsey SM, Li JY, Yang CS, Guo W, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res 1994;54(7 Suppl):2029s-31s. https://www.ncbi.nlm.nih.gov/pubmed/8137333?dopt=Abstract|
|57.||↵||Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. https://www.ncbi.nlm.nih.gov/pubmed/10217058?dopt=Abstract|
|58.||↵||Padayatty SJ, Levine M. Vitamins C and E and the prevention of preeclampsia. N Engl J Med 2006;355:1065. https://www.ncbi.nlm.nih.gov/pubmed/16957157?dopt=Abstract|
|59.||↵||Padayatty SJ, Levine M. Antioxidant supplements and cardiovascular disease in men. JAMA 2009;301:1336. https://www.ncbi.nlm.nih.gov/pubmed/19336705?dopt=Abstract|
|60.||↵||National Cancer Institute. High-Dose Vitamin C – Health Professional Version. https://www.cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq#section/_14|
|61.||↵||Cameron E, Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact 1974;9:285-315. https://www.ncbi.nlm.nih.gov/pubmed/4430016%20?dopt=Abstract|
|62.||↵||Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 1976;73:3685-9. https://www.ncbi.nlm.nih.gov/pubmed/1068480?dopt=Abstract|
|63.||↵||Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 1985;312:137-41. https://www.ncbi.nlm.nih.gov/pubmed/3880867?dopt=Abstract|
|66.||↵||Bruno EJ Jr, Ziegenfuss TN, Landis J. Vitamin C: research update. Curr Sports Med Rep 2006;5:177-81. https://www.ncbi.nlm.nih.gov/pubmed/16830410?dopt=Abstract|
|67, 76.||↵||Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 2006;174:937-42. https://www.ncbi.nlm.nih.gov/pubmed/16567755%20?dopt=Abstract|
|69.||↵||Shekelle P, Morton S, Hardy M. Effect of supplemental antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cardiovascular disease. Evidence Report/Technology Assessment No. 83 AHRQ Publication No. 03-E043. Rockville, MD: Agency for Healthcare Research and Quality, 2003. https://www.ncbi.nlm.nih.gov/pubmed/15040141?dopt=Abstract|
|70, 71.||↵||Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 2008;105:11105-9. https://www.ncbi.nlm.nih.gov/pubmed/18678913?dopt=Abstract|
|72.||↵||Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A 2005;102:13604-9. https://www.ncbi.nlm.nih.gov/pubmed/16157892?dopt=Abstract|
|73.||↵||Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A 2007;104:8749-54. https://www.ncbi.nlm.nih.gov/pubmed/17502596?dopt=Abstract|
|74, 82.||↵||National Cancer Institute. High-Dose Vitamin C –Health Professional Version. https://www.cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq|
|75.||↵||Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A 1989;86:6377-81. https://www.ncbi.nlm.nih.gov/pubmed/2762330%20?dopt=Abstract|
|77.||↵||Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 2008;105:11105-9.https://www.ncbi.nlm.nih.gov/pubmed/18678913?dopt=Abstract|
|78.||↵||Levine M, Espey MG, Chen Q. Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free Radic Biol Med 2009;47:27-9. https://www.ncbi.nlm.nih.gov/pubmed/19361554?dopt=Abstract|
|80.||↵||Seifried HE, Anderson DE, Sorkin BC, Costello RB. Free radicals: the pros and cons of antioxidants. Executive summary report. J Nutr 2004;134:3143S-63S. https://www.ncbi.nlm.nih.gov/pubmed/15514289?dopt=Abstract|
|81.||↵||Natural Medicines Comprehensive Database. Vitamin C. http://naturaldatabase.therapeuticresearch.com/home.aspx?cs=&s=ND|