Vitamin C Against Depression: Dose or Megadose?

Vitamin C?

Vitamin C or L-ascorbic acid is an essential and one of the most important nutrients for humans. Ascorbate (an ion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms, apes and humans being a notable exception. Deficiency in this vitamin causes scurvy in humans.

Scurvy has been known since ancient times. People in many parts of the world assumed it was caused by a lack of fresh plant foods. The British Navy started giving sailors lime juice to prevent scurvy in 1795. Ascorbic acid was finally isolated by 1933 and synthesized in 1934.

In 1935, Dr. Jungeblut, then professor of bacteriology at Columbia University, published vitamin C's effectiveness at preventing and treating polio and inactivating the diphtheria toxin. He later found that the vitamin C ascorbates inactivated tetanus as well.

In the 1940s, Dr. Frederick Klenner, a specialist in chest diseases, successfully cured 41 cases of viral pneumonia using high doses of vitamin C. He published his extensive findings in the February 1948 issue of the Journal of Southern Medicine and Surgery. Dr. Klenner ended up publishing 28 articles in various scientific publications.

Mild Vitamin C Deficiency

Even moderately low levels of vitamin C have been linked to depression. A study published in the January 2011 issue of the "American Journal of Geriatric Psychiatry" found that low levels of vitamin C were correlated with both depression and higher mortality rates. While correlation does not establish causality, these results suggest that it is prudent for older people to include more citrus fruits, lightly cooked green vegetables and salads in their diets. If they are unable or unwilling to cook, a supplement may be advisable.

In another study, Dr. L. John Hoffer MD PhD, an investigator at Jewish General Hospital affiliate Lady Davis Institute for Medical Research, randomly assigned admitted patients to receive either vitamin C or vitamin D supplements for seven to ten days. Those given vitamin C had a “rapid and statistically and clinically significant improvement in mood state” which did not occur with vitamin D.

Dr. Hoffer says that earlier studies indicate that about “one in five acute-care patients in the hospital have vitamin C levels so low as to be compatible with scurvy. Subclinical deficiencies of vitamin C and vitamin D have each been linked to psychological abnormalities.”

The brain is the second biggest body user of vitamin C. The nutrient aids in tissue growth and repair and in the production of neurotransmitters, particularly norepinephrine which is critical for both function and mood. Vitamin C catalyzes the manufacturing of serotonin, a brain chemical and neurotransmitter, responsible for our mood. It is therefore a critical supplement for individuals with low level serotonin associated depression.

Dr. Hoffer adds that the treatment is “safe, simple, and cheap, and could have major clinical practice implications.”

Actually, similar correlation between vitamin C deficiency and clinical depression was supported by multiple studies. Recent study of hospitalized psychiatric patients showed that upon admission 25% were deficient in folic acid, 32% had deficient levels of vitamin C, and 10% had actual scurvy. In addition, suboptimal levels of vitamin B 12 were found at 30 times the prevalence of the general population. A deficiency in any one of these nutrients can cause an imbalance in the nutritional environment of the brain.

Vitamin C and Neurotransmitters

The link between vitamin C deficiency and depression may be caused by lower neurotransmitter levels. According to an August 2003 article in "Nutrition Journal," vitamin C works together with the enzyme dopamine-beta-hydroxylase to convert dopamine into norepinephrine, which plays an important role in the regulation of mood.


Mark Riordan, M.D., a specialist in orthomolecular medicine, states that 30 percent of depressed patients who receive vitamin C supplements will improve. Since this rate of improvement is below the level produced by many placebos, many studies fail to find a significant effect for this treatment. Nevertheless, it may make an important difference for particular individuals, especially if they have low levels of this nutrient.

If you are under stress, research published in the April 1998 issue of the "Journal of General Psychology" suggests that you may want to add vitamin-C-rich foods or supplements to your diet. Ethical guidelines preclude intentionally inflicting distress on humans, but animal models of depression show that animals subjected to unavoidable electric shocks had tissue levels of vitamin C that were between 20 and 30 percent below unstressed animals.

A 2002 German University study of 120 college students, tested the impact Vitamin C had on the anxiety response of students, when they were subjected to a stressful situation – public speaking.  Students, who did not get the 1,000 mg dose of Vitamin C, had significantly higher levels of cortisol and blood pressure. 

In an animal study, rats who were subjected to stress, and who did not receive vitamin C supplements, had three times the level of cortisol in their blood.  An added benefit is the reduction of belly fat. 

How it works?

Animals show steady and significant production of vitamin C throughout the day and night and when any stress occurs, physical, such as illness or injury, or mental, such as being caged, transported, abused, or chased, need for and production of vitamin C dramatically increases. For example, goats make the human equivalent of 13,000 mg daily, and significantly more, as much as 100,000 mg, when under stress.

The pituitary and adrenal glands have one of the highest tissue concentrations of vitamin C. In healthy vitamin C producing animals pituitary ACTH and then adrenal cortisol production rises when stressed, and concurrently, vitamin C production, increasing serum vitamin C. A sufficiency of vitamin C enhances the production of ACTH, cortisol and adrenaline (epinephrine) so that the initial response to stress is improved.

Animals perceive stress, other than illness or injury, as the need for 'fight or flight'. Sanity (well-being) requires we subdue our enemies or we run away from them. No animal stays healthy remaining with an un-subdued enemy (either get away, or turn your enemy into a friend). The initial encounter requires an adequate response.

Among other benefits, increased cortisol and epinephrine allow more powerful punches or faster running from danger (fight or flight) and less inflammation if ill or injured. The production and release of large amounts of vitamin C concurrently or immediately following cortisol release rapidly reduces cortisol and epinephrine to within normal range, the pre-stressed state.  In animals not producing vitamin C, or those with lower production due to aging, chronic stress may lead to reduction in body stores of vitamin C, exhaustion of epinephrine production and inappropriately elevated cortisol. This has great downsides.

Excess cortisol or inappropriately timed cortisol will slow healing and when dis-regulated contributes to anxiety and mood disorders, insulin resistance, obesity, metabolic syndrome, insomnia and fatigue.  Excessive stress may eventually lead to low cortisol and adrenal exhaustion.

A primary why reason animals suffer less or not at all from these conditions is because they make their own vitamin C. The post stress production of abundant vitamin C and return of cortisol levels to unstressed ranges, restores tissue vitamin C to be ready for future stress. Humans also release vitamin C during stress but they must take from body stores and as tissue levels are depleted (no GLO) the ability to recover from stress is reduced and eventually lost.

How it works - I am stressed, my cortisol and epinephrine rise, I deal successfully with the stress, as my vitamin C rises (in humans not produced but taken from serum and tissue stores) I return to my healthy, normal, state - unstressed.

Dosage for Depression

Adults are recommended by the National Academy of Sciences to consume at least 75-90 milligrams of vitamin C each day through food or supplement sources, enough to prevent Scurvy, but not enough to help with depression anxiety.  A 1,000 mg Vitamin C supplement in addition to the amount found in a multivitamin should be used. For those clinically deficient, the upper tolerable level for adults is 2,000 mg per day, but large doses may cause indigestion, nausea, and diarrhea.

There is a group of specialists who consider the standard recommended dosage as absolutely not sufficient for the positive effect to get noticed for many serious diseases.

In their book Ridiculous Dietary Allowance, An Open Challenge to the RDA for Vitamin C, Hickey and Roberts discuss many of the problematic issues regarding the current RDA and DRI. They suggest a minimum daily dose of 3,000 mg, 1,000 mg with each meal. They claim that ‘with each meal’ part is very important. Other living creatures producing vitamin C do so all day long. Hickey and Roberts support their recommendations with science and logic. In disease states their recommended daily dose is higher, 6,000-16,000 mg daily for heart disease; 14,000-39,000 mg if you have cancer. Animals produce vitamin C all day long and increase production when stressed. Humans taking 100 mg once a day do not come near real sufficiency and even higher doses taken just once a day won’t provide the serum levels necessary to maintain tissue levels of vitamin C.

The multi-dose supporters claim that the restriction on the dosage from official organizations are not justifiable, citing the outcomes of eight placebo-controlled, double-blind studies and six non-placebo controlled clinical trials in which up to 10,000 milligrams of vitamin C was consumed daily for up to three years, which may suggest the safety of vitamin C pills in excess of the RDA.

The uses and recommended daily intake of vitamin C are matters of on-going debate, while most moderate experts recommend the dosage of 1,500 mg, consumed three times a day in equal doses of 500 mg. And complement the supplements with healthy diet rich in this and other nutrients.

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