Oct 17, 2017

Vitamin C and cancer – the evidence reviewed

Inadequate levels of vitamin C should be avoided by the daily consumption of vitamin c rich foods as low levels are linked to a higher risk of degenerative diseases including arthritis, dementia and cancer. Taking more than necessary, particularly with ascorbic supplements, has not been shown to reduce cancer risks compared to those with adequate levels. In two large well conducted randomized controlled trials, high dose oral vitamin did not slow cancer progression. To date, no randomized trial has compared high-dose intravenous Vitamin C with placebo within a statistically robust design.

Vitamin C, ascorbic acid, is an essential water-soluble nutrient which cannot be made, in our bodies as we lack the enzyme L-gulonolactone oxidase required for ascorbic acid synthesis. It also only lasts for a short period of time in the body so should be ingested regularly. Fortunately, it is commonly available in a wide variety of citrus fruits, berries, vegetables, nuts and herbs.

 

Biochemical roles in the body:

Vitamin C is needed for the growth and repair of tissues in all parts of your body. It helps the body make collagen, an important protein used to make skin, cartilage, tendons, ligaments, and blood vessels. Vitamin C is needed for healing wounds, and for repairing and maintaining bones and teeth. It also helps the body absorb iron from non-haem sources.

Vitamin C is also an antioxidant, along with vitamin E and beta-carotene. Antioxidants block some of the damage caused by free radicals, substances that damage DNA. The build up of free radicals over time may contribute to the aging process and the development of health conditions such as cancer, heart disease, and arthritis. Vitamin C may have cancer protective properties by limiting the formation of carcinogens, such as nitrosamines. More specifically, Vitamin C is involved in the mechanism that enables DNA to ‘sense’ the damage done by free radicals produced from carcinogens, by integrating with the iron imbedded in DNA. This process facilitates DNA repair and is therefore a significant aspect of immune surveillance. This is an important factor in the first stage of cancer development, as it prevents mutation and gene rearrangement. This protection is needed every minute of every day as, according to estimates, each cell in the body can be expected to experience approximately 100,000 potentially DNA-damaging events daily. So a healthy DNA repair system is imperative. Vitamin C has also been shown to protect intracellular components from toxic products such as hydrogen peroxide via inhibition of gap-junction intercellular communication. Finally vitamin C is a cofactor for several enzymes that play an important role in the synthesis of collagen.

Recommended daily amount:

The RDAs for vitamin C are based on its known physiological and antioxidant functions in white blood cells and are much higher than the amount required for protection from deficiency in adults this is between 80-100mg /day. Men need 10% more than women until they pregnant or lactating when the RDA is around 120mg/day. Smokers should take another 35% (around 120-140 mg/day). Normal blood levels are between 34-114 micromols/l.

Vitamin C deficiency

Screen Shot 2017-10-17 at 16.58.38Severe deficiency of vitamin C results is commonly called scurvy. With little or no intake (below 10 mg/day) initial symptoms can start within 1 month and include fatigue (probably the result of impaired carnitine biosynthesis), malaise, and inflammation of the gums. As vitamin C deficiency progresses, collagen synthesis becomes impaired and connective tissues become weakened, causing haemorrhagic skin changes such as petechiae, ecchymoses, purpura, joint pain, poor wound healing, hyperkeratosis, and corkscrew hairs. After more time, individuals develop depression, swollen, bleeding gums and loosening or loss of teeth due to weak tissues and blood vessels. Scurvy was responsible for the miserable deaths of thousand British sailors during the mid-1700s until Sir James Lind, a British Navy surgeon, determined that eating limes and other citrus fruits could prevent scurvy. The subsequent improvement in health of British sailors gave the navy a military advantage and the nickname Limies that sticks today.

Inadequate vitamin C levels.

In Today’s society scurvy is rare, although can still be found amoung elderly people in social isolation or those with mental illness, especially if they smoke heavily. More relevant is health implications of having chronically low levels which as been linked with an increased risk of a important degenerative conditions such as high blood pressure, macular degeneration, gallbladder disease, atherosclerosis, heart attacks and stroke. Higher than normal levels, especially produced through supplemental ascorbic acid, have not been shown to reduce the incidence of these disease. Low levels are thought to increase vulnerability to the common cold but again taking high amounts, especially after a cold has developed has not been shown to reduce its during although it may help symptoms of a blocked nose due to the anti-histamine effect of high-dose vitamin C rather than a direct attack on the virus.

The evidence for vitamin C and cancer prevention

Most case-control studies and epidemiologic evidence suggests that higher consumption of fruits and vegetables is associated with lower risk of most types of cancer including lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus. This may, in part, due to their high vitamin C content although fruit also contains other healthy components including fibre, other vitamins, minerals and polyphenols. Evidence from prospective cohort studies is compounded by the issue that people who eat more fruit are generally more health conscious, less likely to smoke, be overweight and more likely to exercise. There are some studies which large enough for the statistician to exclude these other influences in the statistical analysis. For example in the massive Nurses’ Health Study, consumption of an >200 mg/day of vitamin C from food compared with < 70 mg/day was associated with a lower risk of breast cancer especially premenopausal women with a family history. On the other hand, two other large cohort trial found no increase in cancer if individuals consumed over 87mg/day and certainly no reduction if they consumed over 200mg/day. It appears, from this data that taking over the required amount of vitamin C does not reduce cancer risk but being deficient does increase the risk.

Most randomized controlled studies, investigating the potential anti-cancer properties of vitamin C supplements have combined them other micronutrients. For example, 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 supplementation with 120 mg ascorbic acid, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, and 20 mg zinc, or placebo. After a median follow-up time of 7.5 years, men, in the supplementation group had lowered total cancer incidence. Further analysis of dietary habits of men in the study relieved many had inadequate intake of these nutrients and they like explanation for the benefit and the supplement restored the level to the normal range.

In the Physicians’ Health Study II, supplements containing 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. Similar findings were reported in women participating in the Women’s Antioxidant Cardiovascular Study. 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. Likewise, 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.

A 2008 review of vitamin C, beta-carotene, vitamin A, or vitamin E found no convincing evidence that vitamin C (or) prevents gastrointestinal cancers. 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.

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. 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 – on the other hand if they were low they may well have helped.


Sources of vitamin C

 

LeavesCitrus fruits, berries and vegetables are the best sources of vitamin C. Acerola cherries, guarvas, yellow peppers, blackcurrents and blackberrreis are particularly rich in vitamin C. There levels of vitamin C and other healthy polyphenols are very much higher in the wild rather than industrial farmed varieties. In a typical western diet, although potatoes only have a low concentration of vitamin C, because they are eaten in such large amounts they are substantial contributors to the national daily intake. Other food sources include red and green peppers, kale, nuts, kiwifruit, broccoli, strawberries, peas and Brussels sprouts. It is present in high concentrations in many herbs particularly coriander, thyme and mint. Spices such as chili, paprika and black pepper have a high concentration but have a lower contribution to the daily amount as they are usually taken in small amounts. Although vitamin C is not naturally present in grains, it is added to some fortified breakfast cereals. The vitamin C content of food may be reduced by prolonged storage and by cooking because ascorbic acid is water-soluble and is destroyed by heat. Steaming or even short microwaving may lessen cooking losses. Fortunately, many of the best food sources of vitamin C, such as fruits and some vegetables, are usually consumed raw. Some dried food concentrates preserve their high vitamin C content, particularly rose hips. Consuming five varied servings of fruits and vegetables a day can provide more than 200 mg of vitamin C. Improvements in food logistics have ensured that the availability of fruits from around the world has never been so good. Both conventional fruits and exotic varieties often have high levels of vitamin C. As fruit ripens the vitamin C content increases, as well as the natural salycilates, so don’t be put off by a few soft bits!

Fruit juices and smoothies These are a reasonable way to increase your fruit intake but they also increase the effect of the sugar by speeding up how quickly it is absorbed into the blood stream (glycaemic index). Most juice and smoothie aficionados mix them with plenty of vegetables but an increasingly used and sensible phrase used in healthier circles is; “Eat your fruit and juice your vegetables” If you do make fruit juices, ideally they should be drunk fresh. After squeezing, juice changes its chemical composition quickly becoming more acidic and losing its nutritional content. Juices within cartons have generally been heavily processed increasing their sugar content and often need the vitamin C re-added to keep the levels up. Many also have added extra sugar and these should definitely be avoided. Despite the drawn back of juices they are still a better alternative than sugary canned drinks so on a hot summer day consider a freshly squeezed orange mixed, mint, water and ice which may entice kids to more a healthier option. One lemon squeezed into a pitcher with a spoon of honey topped up with sparkling water makes healthier lemonade for children.

Fruit intake and indigestion: People often say – “I can’t eat fruit because I have indigestion or heartburn”. Although it is true that initially fruit can result in a little irritation in vulnerable individuals, it is not the root cause of the problem and in the long term fruit will improve the health of the stomach and oesophagus (gullet). The underlying cause is usually an unhealthy balance of fat, meats and sugar which the stomach has to work harder to digest – i.e. produce more of its own hydrochloric acid. To make matters worse, sufferers often turn to antacids for immediate relief. The stomach then senses a more alkaline environment and responds by producing yet more acid, perpetuating the problem. On the other hand, consumption of mildly acidic fruit sends signals to the stomach lining to produce less of its own acid. After a while, with perseverance, eating fruit and other less gastric-irritating foods will therefore reduce the acid levels and improve the health of gastric lining, and thus prevent indigestion.


 

The evidence for high dose vitamin C in the treatment of cancer

 

Studies have shown that vitamin C can be safely administered to healthy volunteers or cancer patients at doses up to 1.5 g/kg with  screening to eliminate treating individuals with risk factors for toxicity such as g-6-p dehydrogenase deficiency, renal failureand renal stones.  These studies have also found that blood concentrations of vitamin C are higher with IV administration than with oral administration and are maintained for more than 4 hours.

In the 1970s a Scottish surgeon, Ewan Cameron, his colleague, Allan Campbell and chemist Linus Pauling worked on the potential links between vitamin C and cancer. It is often misquoted that this research won a Nobel prize. This is incorrect; Professor Pauling won a Nobel prize in 1954 for his work on chemical bonds winning, 25 years earlier.

In 1975, they published acase report of a single patients reported improvement in well-being and resolution of lung masses after being treated with IV ascorbic acid. When the patient’s daily dose of ascorbic acid was reduced, some of signs of the disease returned; however, remissionwas temporarily achieved again after the patient reverted to the higher initial dose.

In 1976 a 100 patients with terminal cancer were treated with oral ascorbate (10 g/day for 10 days IV, then orally) were compared with non-randomised matched controls from the same hospital and reported better survival rates of around 300 days.

In 1979 and 1985 the first randomized placebo controlled trials were conducted but used either 10 g or oral vitamin C or placebo daily until signs of cancer progression. At the end of each study, no significant differences were noted for symptoms or survival.

In 2006 a further three case reports were published involving IV Vit-C amoung terminal cancer patients who received between 15 g to 65 g, IV initially once or twice a week for several months. Patients also used additional treatments, including other vitamins and plant extracts The authors felt survival was longer than expected but there were no controls to compare with.

In 2007 and 2011, two non randomized studies demonstrated that IV vitamin C treatment resulted in improved quality of life and decreases in cancer-related side effects in cancer patients but again their were no controls to compare with. Other trials have combined vitamin C with chemotherapy with reported improvements in toxicity but as no disease outcomes were used we do not know whether vitamin C just reduced the effect of chemotherapy.


 

Conclusion:

Inadequate levels of vitamin C should be avoided by the daily consumption of vitamin c rich foods as low levels are linked to a higher risk of degenerative diseases including cancer. Taking more than necessary, particularly with ascorbic supplements, has not been shown to reduce cancer risks compared to those with adequate levels. Although there were some suggestions from early non-randomised trials, high dose oral vitamin did not slow cancer progression in two large well conducted randomized controlled trials. To date, no randomized trial has compared high-dose intravenous Vitamin C with placebo within a statistically robust design. A trial is needed to solve the IV vitamin C dilemma although this lack of data has not stopped many nutritional therapist promoting high dose IV vitamin in their routine practice.


 

References:

 

Cameron E, Campbell A: The orthomolecular treatment of cancer. Clinical trial of high-dose ascorbic acid in advanced human cancer. Chem Biol Interact 9 (4): 285-315, 1974

Cameron E et al: Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy. Chem Biol Interact 11 (5): 387-93, 1975.

Cameron E, Pauling L: Ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci 73 (10): 3685-9, 1976

Cameron E, Pauling L: Supplemental ascorbate in the treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci 75 (9): 4538-42, 1978.

Creagan ET et al.: Failure of high-dose vitamin C therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 301 (13): 687-90, 1979

Moertel CG, et al.: High-dose vitamin C versus placebo in patients with advanced cancer who have had no prior chemotherapy. RCT. N Engl J Med 312 (3): 137-41, 1985.

Padayatty SJ, Riordan HD, Hewitt SM, et al.: Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 174 (7): 937-42, 2006.

Vollbracht C et al.: Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study In Vivo 25 (6): 983-90, 2011.

Yeom CH, Jung GC, Song KJ: Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci 22 (1): 7-11, 2007.

Padayatty SJ: Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140 (7): 533-7, 2004.

Hoffer LJ: Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19 (11): 196

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