The Role of Histamine in Mental Illness and Its Attenuation With Vitamin C – Part II
pathway. Studies have shown that Ca2+ release is increased in major depression (Kusumi, Koyama, & Yamashita, 1991). The protein calcineurin is downstream of the release of Ca2+. As mentioned above, calcineurin is involved in neurotransmitter depression. Histamine and calcineurin are both involved in mental illness and allergic reactions (Abbas, Lichtman, & Pober, 2000); therefore histamine’s activation of calcineurin may play a key role in both of these morbid outcomes.
Additional evidence for the potential morbidity of the IP3 pathway is that H1 receptor activation can inhibit learning and memory (Knoche et al., 2003), cause hyperactivity (Chiavegatto, Nasello, & Bernardi, 1998), and cause aggression (Yanai et al., 1998). An H2 receptor mutation can result in schizophrenia (Brown, Stevens, & Haas, 2001). Some antihistamines can reduce anxiety by antagonizing the H1 receptor (Lader & Scotto, 1998), while H2 antagonists can have antidepressant effects (Cantu & Korek, 1991). Both H1 and H2 antagonists can cause a wide variety of physical and mental side effects.
Increased histamine levels result in increased vitamin C utilization (Nandi, Subramanian, Majumder, & Chatterjee, 1974); this strongly suggests that vitamin C regulates histamine levels via its antihistamine effect. Vitamin C is a very efficient histamine detoxifier (Clemetson, 1999). “After two weeks of 2,000 mg vitamin C per day, the blood histamine level fell about 40% below the baseline value” (Johnston, Retrum, & Srilakshmi, 1992, p. 989). Vitamin C raises the level of cAMP (Tisdale, 1975), a key molecule in the mental health-enhancing cAMP pathway. Perhaps just as importantly, cAMP inhibits histamine release (Cathcart, 1986). Conversely, low cAMP levels can increase histamine release (Mohsenin & Dubois, 1987).
Chapter 4: Results and Findings
Introduction:
In Chapters 1 and 2 this dissertation established a theoretical framework in which vitamin C attenuates histamine-mediated mental illness. In Chapter 4, data will be presented that exemplifies the multitude of positive effects on the body by vitamin C, including positive effects on mental illness. It has been known for some time that vitamin C is a key nutrient for proper brain function (Mark & Mark, 1989). Vitamin C’s positive role in mental health is illustrated by its potential to reduce anxiety when large doses are used (Balch & Balch, 1997). It also has a mild antidepressant effect (Brody, 2002). Conversely, vitamin C deficiency consistently produces behavioral abnormalities and fatigue, in addition to the classic skin lesions seen in scurvy (Petrie & Ban, 1985; Kallner, 1987). When vitamin C levels are low, the CNS and brain attempt to maintain a normal tissue level by depleting other tissues of vitamin C (Rose, 1988). This finding begs the question of how low or high vitamin C levels can affect mental health, if the CNS and brain constantly strive to maintain homeostasis of this vitamin. An explanation of this theoretical question is found in the Conclusions and Implications section of Chapter 5.
Analysis of Data: N/A
Findings:
Vitamin C induces myelin formation, membrane enzyme activity, hormone synthesis, acetylcholine and norepinephrine release, and also influences neurotransmitter binding, neurotransmitter receptor distribution, and neurotransmitter density (Rebec & Pierce, 1994). At physiological pH (7.4), “ascorbic acid causes a concentration-dependent increase in the affinity of 5-hydroxytryptamine (5-HT) for 5-HT3 binding sites” (serotonin receptor 3 sites) (Katsuki, 1996, p. 299). Vitamin C also modulates dopamine levels. High brain dopamine levels are associated with psychosis. This can be achieved with chronic use of the stimulant amphetamine. Traditional antipsychotic drugs lower dopamine levels, and are called neuroleptics. Vitamin C experimentally has a neuroleptic-like action, in that it inhibits amphetamine-induced locomotion, presumably via inhibition of dopamine-stimulated neurotransmission (Rebec & Pierce, 1994). When the potentially neurotoxic neurotransmitter glutamate is injected into animal brain, there is a dramatic increase in extracellular vitamin C release (Katsuki, 1996).
There are a number of ways in which vitamin C improves mental health. Vitamin C increases secretion of the hormone oxytocin, which heightens arousal and well-being (Brody, 2002). “Ascorbate promotes myelin formation” (Rice, 2000, p. 214), which is critical for proper nerve function. Vitamin C supplementation inhibits stress-induced cortisol release, and reduces stress-related mortality (Brody, Preut, Schommer, & Schurmeyer, 2002). Intake of vitamin C at 4 g/day significantly reduced cortisol levels, and increased levels of the androgen steroid hormone dihydroepiandosterone (DHEA) (Komindr, Nichoalds, & Kitabchi, 1987).