Pauline Anderson

May 01, 2014

PHILADELPHIA — A new study finds a link between vitamin C depletion and increased risk for intracerebral hemorrhage (ICH).

In a case–control study, researchers found vitamin C depletion was more common among ICH cases than matched controls.

"This original study suggests that a low plasma vitamin C concentration is a risk for spontaneous intracerebral hemorrhages," lead researcher Stephane Vannier, MD, a neurologist at Pontchaillou University Hospital, Rennes, France, told Medscape Medical News.

"This link is probably associated with the role of vitamin C in blood pressure regulation and collagen biosynthesis," although other factors may also play a role, said Dr. Vannier.

These findings, he added, provide the rationale for clinical trials to test the efficacy of vitamin C supplementation in preventing hemorrhagic stroke and minimizing infectious or cutaneous complications in those sustaining an ICH.  

Preliminary results of the study were first released in February and were  presented here at the American Academy of Neurology (AAN) 66th Annual Meeting.

Dr. Stephane Vannier

Risk Factors for ICH

The prospective case–control study included 135 participants, whose mean plasma vitamin C concentration was 45.8 µmol/L. Of these participants, 41% had a normal vitamin C status (more than 38 µmol/L), 45% showed some depletion (11 to 38 µmol/L), and 14% were deficient (less than 11 µmol/L).

The vitamin C concentration was significantly lower in the 65 participants who had experienced a spontaneous ICH than in the 65 healthy controls, said Dr. Vannier. However, he and his research colleagues have not yet calculated an odds risk.

The study found that strong risk factors for deep ICH were hypertension (P = .008), alcohol consumption (P = .023), and being overweight (P = .038). The researchers also noted that patients with a lobar ICH were significantly older than those with a deep ICH.

As well as increasing the risk for infection by altering the immune response, vitamin C deficiency has many other health implications. Vitamin C (ascorbic acid) is an effective antioxidant and might counter the oxidative stress that plays a role in the etiology of high blood pressure. Dr. Vannier noted that most hypertensive patients in the study were vitamin C depleted.

Not getting enough vitamin C may increase risks for atherosclerosis and heart disease, as well as hypertension.

"Vitamin C decreases blood pressure, which may partly explain the association between fruit and vegetable intake and mortality from stroke," said Dr. Vanier. "Moreover, ascorbic acid contributes to collagen biosynthesis and regulation, including that of basal membrane vessel type IV collagen. Depletion is responsible for unstable and dysfunctional collagen with loss of organ support properties, which may lead to hemorrhages."

Boosting Vitamin C Intake

The study authors made several other important observations. For example, length of stay in the neurology care unit was significantly shorter (9.8 days) for patients with normal vitamin C status than for those with vitamin C depletion (18.2 days).

The longer hospital stay may be the result of complication-related infections in patients with a vitamin C deficiency, said Dr. Vannier. Or, those with vitamin C depletion may be dealing with skin disorders, such as ulcerations, pressure ulcers, and delayed healing of existing lesions.

"Larger studies are needed to explore these relationships and hypotheses, but it seems that we should be treating vitamin C deficiency with ascorbic acid supplementation and increased fruit and vegetable intake to limit infectious and cutaneous complications," said Dr. Vannier.

Environmental factors are probably also involved in the relationship between vitamin C deficiency and ICH, but more studies are needed in this area, too, said Dr. Vannier.

Experts recommend 120 mg of vitamin C daily, according to Dr. Vannier. Although a balanced diet with plenty of fresh fruit and vegetables should provide adequate levels, patients might try boosting their intake of foods rich in the vitamin, such as raw peppers (any kind), which contain about 200 mg/100 g; fresh orange juice, which has about 60 mg per 100 g; black currants; or parsley.

At this point, experts don't recommend vitamin C supplementation if there is no deficiency, said Dr. Vannier. 

The vitamin C–ICH connection is not far-fetched, the researchers note. Hemorrhagic syndrome and occasionally ICH were among the clinical manifestations of scurvy, a devastating disease of vitamin C deficiency that plagued sailors of bygone years who didn't have access to fresh fruit and vegetables.

A Unique Question

For a comment, Medscape Medical News approached Shyam Prabhakaran, MD, associate professor, neurology, Northwestern University, Chicago, Illinois, who cochaired a session on cerebrovascular disease and interventional neurology here.

Dr. Prabhakaran said he found the work interesting but very preliminary in that it's only a case–control study.

"It's definitely probing a unique question that has not been asked before," he said. "It's suggestive that some sort of nutritional depletion of vitamin C may be a risk factor for somebody developing a bleeding in the brain, but the results need to be verified in a prospective study."

Dr. Prabhakaran surmised that lack of vitamin C could weaken blood vessels and that this might lead to these vessels becoming more prone to bleeding "perhaps under the condition of high blood pressure."

In that situation, vitamin C depletion could in a sense be a kind of "potentiator," he added.

In any case, the research "clearly warrants further evaluation," said Dr. Prabhakaran.

The study was supported by the University of Rennes, France.

66th Annual Meeting of the American Academy of Neurology, April 26 to May 3, 2014. Abstract 3101.

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