D3?

Vitamin D (as well as vitamin D supplements) actually comes in two forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol).  Although once thought to be equivalent, it is now known that vitamin D3 (manufactured from exposure to UVB rays) is not absorbed by the skin right away.  It actually takes up to 48 hours before the majority of the vitamin D you have been exposed to has entered your bloodstream.

What’s the big deal?

After a nice, sweaty day spent outside, what’s the first thing we want to do?  Take a shower.

And what do we typically do in the shower?  Lather on lots of sudsy soap.

Uh oh.  The problem here is that you are not just washing away your sweat with that soap.  If it’s been less than 48 hours, you are stripping your skin of all that precious vitamin D!

The solution?  Well, there are a couple:

#1: Wait two days to shower

I may not wear makeup or lots of fancy accessories, but I am still a lady.

I am not WAITING two days after sweaty time in the sun to rinse off!

#2: Only use water

I like to take a shower almost everyday so this is my personal preference.

I know, I know.  Only water?!

If you eat a healthy, low fat raw diet, without added salt, spices, or condiments, you really do not need to use soap.  In fact, I NEVER use any form of soap, natural or not, to clean my skin.

But I’ll save that for another post.

Problems with Supplementation

The research out there on problems with supplementation of any kind, including vitamin D, is rather extensive.

One particular study conducted in 2008 showed that vitamin D supplementation can actually block the Vitamin D Nuclear Receptor (VDR), which is necessary for the “repression or transcription of hundreds of genes, including genes associated with diseases ranging from cancers to multiple sclerosis.”

Here is a quote from the professor at Australia’s Murdoch University School of Biological Medicine and Biotechnology, Trevor Marshall, Ph.D., as quoted in a ScienceDaily article on the study:

Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics of chronic disease, such as heart disease and obesity, are just getting worse.

Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness,’ Marshall added. ‘Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively.

Debbie Took from RawforLife makes a very good point regarding supplementation and animals in the United Kingdom:

The animal world is full of clues as to how to live healthfully. So, as looking at domesticated mammals (ingesting various unnatural substances in their feeds) would complicate things, let’s consider wild mammals such as squirrels, deer, rabbits. They don’t supplement (and neither do they eat oily fish or vitamin D-fortified milk).

Sure, they’ll get lots more sunlight each summer than we will (which gives us a clue as to lifestyle adjustments to be made). However, the supplement manufacturers like to make us feel that no matter how much sunshine we get in the UK summer our health is going to be compromised if we don’t take D supplements in the winter. Yet these animals are doing just fine! (but note they don’t sit behind windows, soap themselves down daily, drink alcohol or overeat either…)

Well said, Debbie!

I think I’ll take a lesson from my animal friends and stick with simple (and free) sunshine.

What About Winter Weather?

Because vitamin D is fat-soluble, it can be stored by the body.  This means that you have the potential to get enough sunshine during the warm months to last you through the winter.

But don’t think you can’t get a wicked tan in the winter time.  Did you know that you can get pretty seriously burned from sunlight that is reflected off of snow?

Now, you won’t catch me sunbathing in 30 degree weather and I certainly do not recommend it.  But if you’re a fan of cold weather (or a masochist), be my guest!

My Advice to You

If you haven’t already, be sure to make the most of the last couple of weeks of mild weather before it gets too cold.

Remember, all it takes is 15-30 minutes outdoors (unless you have dark skin, in which case you will require more exposure) to receive adequate vitamin D.

You can spare a few measly minutes for your health, right?

Vitamin D also called as vitamin D3 or ‘cholecalciferol’; is a fat-soluble vitamin. Human beings are dependent on the sun exposure to fulfill their needs of vitamin D. It is uv-B radiation that are being absorbed by 7-dehydrocholesterol present in the skin that aids in converting previtamin D3 to vitamin D3. Vitamin D is essential for the development of bones and also to enhance calcium and phosphorus uptake from the intestine. It assists in the oscillation of calcium ions between bone and blood. It is therefore vitamin D is essential component for all age groups; during infant to childhood stage it plays an essential role in bone development or else its deficiency results in bone deformation and rickets. In adults its deficiency results in softness of bone leading to osteomalacia. (Goldman, 2004).

Vitamin D3 once formed goes into circulation and is converted to 25 hydroxyvitamin D3 in liver, again released in circulation and subsequently converted to the active form of vitamin D, 1, 25- dihydroxyvitamin D3 in kidney. It is observed that Vitamin D deficiency remains unrecognized and therefore its insufficiency is taking a shape of epidemic among children and adults in United States.

Various research studies have been carried out throughout the world to conclude that vitamin D plays an imperative role not only for the bone health but also for various kinds of cancers, diseases related to heart, multiple sclerosis, in type I diabetes, also in various autoimmune diseases encompassing rheumatoid arthritis. Therefore, maintenance of suitable blood concentration of 25-hydroxyvitamin D (30 ng/ml) is very essential. As vitamin D is essential for enhancing intestinal calcium absorption, it’s appropriate level in the blood is also necessary for the formation of extrarenal 1?- hydroxylase which plays an imperative role in the formation of 1, 25- dihydroxyvitamin D3 (Holick, 2004).

Production and fate of Vitamin D

When an individual is exposed to sunlight previtamin D3 and also vitamin D3 forms photoproducts which are biologically inert. Vitamin D intake through diet or that formed in the skin with the help of sunlight come into the blood circulation, it reaches liver where it is metabolised to 25(OH)D3 by vitamin D 25-hydroxylase (25-OHase).  25(OH)D3 is again released in the circulation, it reaches kidney and get converted to 1,25(OH)2D3 in presence of enzyme 25(OH)D3 1 -hydroxylase (1-OHase). The renal production of active form of vitamin D is regulated by a variety of features encompassing serum phosphorus (Pi) and PTH. The active form of vitamin D (1,25(OH)2D) is now capable of managing the calcium metabolism. It is observed that the enzyme  25(OH)D 24-hydroxylase (24-OHase) enzyme which plays a crucial role in generating the active form of vitamin D, works on threshold mechanism to keep the check on the production of 1,25(OH)2D3 and if it is produced in higher quantity, the enzyme aids in the degradation of active vitamin D (Holick, 2004).

Further, it is also documented that 1,25(OH)2D can depress the activity of 1 -OHase, and the parathyroid hormone (PTH) can stimulate this activity. Many extrarenal tissues also express the 1 -OHase, these encompass tissues of bone osteoclasts, tissues of skin, macrophages, placenta, tissues of colon, tissues of brain, tissues of prostate, endothelial tissue, and glandular tissues of parathyroid. Extrarenal formation of 1,25(OH)2D3 might participate in the differentiation and proliferation of cell and also in immune response. Consequently, 1,25(OH)2D3  is essential for various physiological processes apart from its well-known function in calcium metabolism. In contrast to renal 1 -OHase, extrarenal 1 -OHase does not respond to stimulation by PTH. Furthermore, 1 -OHase may vary in expression with the physiologic state of a tissue as well as with disease progression (DeLuca, 2004).

Food incorporating Vitamin D

There are various resources of vitamin D, this encompass pure form of Cod liver oil, cooked form of Salmon, Mackerel, Tuna fish and Sardines canned in oil, sardines, margarine fortified, bran flakes, eggs, lamb liver. Fortified foods include milk and milk products especially cheese, orange juice and some breads and cereals (Vitamin D sources- Foods with Vitamin D).

As mentioned, the higher concentration of vitamin D influences the metabolic functions of the body, WHO has recommended intake dose of vitamin D by individuals belonging to different group. Up to the age of 50 years, during pregnancy and lactation the requirement is 200 IU/d, for the age group from 51-65 years it is 400 IU/D for the age of 65+ the requirement exceeds to 600 IU/d (Vitamin D sources- Foods with Vitamin D).

Considering the above data it is manifested that vitamin D is the most essential component for endorsing and preserving the health and vigor of bones as it directly affects the strength of bone in various skeletal and nonskeletal activities of the body encompassing cancers and depression (Lapp, 2009).

Symptoms of Vitamin D deficiency

Fall in plasma calcium and phosphate level, due to insufficient intestinal absorption, renders stimulation of  parathyroid hormone (PTH) secretion to restore serum calcium and bone resorption.

Rickets

In children, the deficient calcification of osteoid tissues result in bony deformities like bow leg, enlarged skull, spinal curvature, chest deformities and hepatosplenomegaly- characteristic features of Rickets. The reason is lack of appropriate bone tissue mineralization, causing soft bones and skeletal deformities. At-risk children are on prolonged exclusive breast feeding without supplementation of vitamin D. Additional risk factors includes vigorous use of sunscreens, and infants placed in daycares, with chances of sun exposure is reduced. Rickets is more prevalent in the children from Asia, Africa and Middle East (Davidson, 2002).

Osteomalacia

In adults decalcification and demineralization of bone leads to osteomalacia which is characterized by bone tenderness with pain and loss of bone density.

This disease is characterized by the aches and pains specifically in the lower back and thighs. Later on, it spreads to the arms and the rib cage.  This pain does not radiate to other areas. It is accompanied by the local tenderness in bones. Another cardinal feature is the weakness of the proximal muscles. This represents as a difficulty in climbing up stairs and getting up from a squatting position.

Due to the deformation of bones, lordosis is a common representation. While walking, the patient shows a waddling gate. Pathological fractures due to weight gain may occur. Despite all these typical signs and symptoms, sometimes chronic fatigue may be the only representing sign (Eisman, 1988).

Osteoporosis

According to an estimate, about more than 25 million adults in United States alone are having or are at risk of developing this disease. This disease is most often associated with an inadequate calcium intake, therefore vitamin D is essential for reducing calcium absorption

Osteoporosis epitomizes reduction in mass of bone, also reduces microarchitectural framework of bone and thereby weakens the tissues of bone and amplifying the risk of fracture. The incidence of osteoporosis and fractures related with osteoporosis raise with age in both males and females, displaying a decline in bone mass with age.

Osteoporosis has emerged as a major health issue in developed nations. It is a condition that depicts frequent fractures, and is expected to influence more of females than males at some stage in their lives. As the age progresses bones become tender leading to osteoporosis in older adults, post menopausal women, non ambulatory individuals and individuals on chronic steroid therapy. The natural rhythm of the body allows a constant remodeling of the bones. In post menopausal women, this ratio is disturbed resulting in a greater amount of bone absorption rather than bone remodeling (Goldman, 2004).

Calcium and Vitamin D

Calcium 500- 1000 mg daily and vitamin D supplements 20µg daily have an established role in  deterrence of elderly fractures, irrespective of whether or not BMD (Bone Mineral Density) values are reduced. This treatment is effective in reducing the danger of fractures related to hip fractures or other kind of fractures in community-living patients. (Davidson, 2002).

Reasons displaying insufficiency of vitamin D

Elevated pervasiveness of lactose intolerance causing undesirable effects with consumption of mild and dairy foods especially in African Americans. Reduced ingestion of vitamin D- equipped food products, predominantly liquefied milk, milk products cereals, because of changing attitude towards health concern and fat intake. Poor intake of calcium rich food encompassing poor intake of milk especially by the young women of reproductive age group thereby reduced concentration of vitamin D and calcium. Augmentation in the use of sun block lotions along with the diminished exposure to sun to avert the chances of skin cancer is also one of the reasons of vitamin D insufficiency. Human milk is meager in vitamin D, in the present era there is enhanced predominance in the duration of breast- feeding ensuing insufficient intake of vitamin D. thus causing low circulation of 25-hydroxyvitamin D concentrations among women. Due to air pollution in industrial areas, the exposure to uv- radiation is reduced and also the poor dietary habits and availability of vitamin D equipped food makes the individual a victim of vitamin D deficiency. In rare cases impaired absorption, enhances body requirement of vitamin D, or enhanced excretion or stringent practice of vegetarianism leads to vitamin D deficiency. In some Arabian countries it is mandatory for women to long robes for religious purpose so their exposure to sun is reduced leading to insufficiency of vitamin D.

(Looker, 2002; Kreiter, 2000; Nesby-O’Dell, 2002).

Vitamin D and Bone Health (BMD, BMC, falls and fracture)

Vitamin D is responsible for forming and sustaining good health of bones by increasing absorption of calcium from intestine and depositing calcium in bones and maintains optimal BMD (Bone Mineral Density). Observation says that diminished absorption of calcium is related to vitamin D; thereby resulting in loss of bone or enhanced chances of osteoporosis (a situation depicting low BMD). Osteoporosis makes the bone fragile making the individual vulnerable to fractures (Cranney et al, 2007).

It is reported by Holick (2006) that vitamin D deficiency causes various bone related anomalies like osteopenia, osteoporosis apart from osteomalacia, resulting in further weakening of muscles and hence exacerbating the risk of falls and fractures. Under such conditions the recommended dose must be increased to 1000 IU/d.

Recommendations for reducing fracture risk with vitamin D and calcium based on clinical studies

            While giving the vitamin D supplements, mostly it is accompanied by calcium in order to obtain the desired results. According to a research study, it was concluded that the combined supplementation of both vitamin D3 and calcium in elderly patient aged 62-85yrs resulted in a decrease in the jeopardy of an individual’s falls, fractures, the bone loss within elderly population. The dose of vitamin D was given as 700-800 IU/day and calcium was given as 500-1200 IU/day.

It is now clearly understood the significance and pivotal role that vitamin D holds in retaining the good health of bone. A number of studies and surveys have been carried out, which strengthen this fact even more. Down here are discussed a few of such studies:

Skin Cancer and Vitamin D

People are now a-days much concerned about the sun exposure resulting in skin cancer. It is observed that chronic and extreme exposure to sunlight in childhood and early stages of life causing sunburns may culminate to increased risk for non-melanoma basal and squamous cell carcinomas (Veierod, 2003; Grodstein, 1995; Kennedy, 2003). Various research studies conclude that melanomas occur in the areas which are not exposed to sun indicating that the vitamin D3 is less synthesised; individuals apply sun protection creams which block UVB radiation responsible for the synthesis of vitamin D3 and the hence they may allow other sun radiations which may cause melanomas (Garland, 1993).

Noncalcemic Actions of Vitamin D

It is known that vitamin D3 interacts with nuclear receptor similar to steroid hormones. As soon as it enters the cell, it passes through the road map of microtubular network to the nucleus. In nucleus it binds with vitamin D receptor (VDR) and generates a complex to generate vitamin D responsive gene (Holick, 1999). 

VDR is present in many tissues of body like small and large intestine, osteoblasts, T and B lymphocytes, ?-islets cells, brain, heart, skin, gonads, prostate, breast and mononuclear cells (Holick, 1999). Studies shows that when 1,25(OH)2D3 if nurtured with leukemic cells of human and mice origin, arrest the propagation and encourage to form grown-up macrophages (Tanka et al, 1982).

1,25(OH)2D3 has come up with antipropagation action that has been proved through clinical trials in psoriasis management. 1,25(OH)2D3 when topically applied, induced a noteworthy progress in various diseases like plaque thickness, scaling and erythema (Holick, 1998). Therefore, this has become the foremost treatment in psoriasis.

1,25(OH)2D3 is playing an imperative role in providing stimulus to the production of insulin (Lee, 1994), inflecting the activation of both B and T lymphocyte (Tsoukas, 1984), direct effect on myocardial contractility (Weishaar, 1987), effect on prevention of inflammatory bowel disease (Cantorna, 2000) and stimulate secretion of TSH.

Deficiency of Vitamin D and its association with to occurrence of autoimmune disorders and cancer

It is observed through various research studies that people living in higher latitudes get less exposure to sun, culminating in vitamin D deficiency and hence accounts for higher incidence of breast cancer mortality rate in north Europe (Grant, 2002).

Vitamin D and Autoimmune Diseases

Data from many animal and human studies shows that vitamin D prevents development of type I diabetes mellitus, rheumatoid arthritis, hypertension, cancers of colon, breast and prostate, Crohn’s disease, multiple sclerosis (Holick, 2004).

Vitamin D Supplementation

            The required amount of vitamin D is difficult to be met from food alone. In some at-risk groups it becomes necessary to give vitamin D-fortified food, or expose them to sunlight. Various at risk groups for vitamin D inadequacy include:

Breastfed infants:

The human milk provides vitamin D with the concentration of 25 IU/L insufficient for the baby. The results of a recent review revealed that a majority of cases of nutritional rickets were found among young African American breastfed infants. According to the recommendations by AAP it is advised that the partially and exclusively breastfed infants should be supplemented with a daily dosage of 400 IU.

People with limited sun exposure:

These include:

People exclusively bound to stay in homes Northern latitude inhabitants Women wearing long robes for religious purposes People with occupations preventing sun exposure

All such individuals must obtain the recommended daily supplemented dosage of vitamin D equivalent to 400 IU in order to prevent them from vitamin D deficiency diseases.

People with dark skin:

These individuals possess a larger amount melanin pigment. Having an excess of this pigment reduces the vitamin D generating ability of skin on sun exposure. It is also suggested in some studies that women of older age, with a darker skin relatively show higher possibility of developing deficiency of vitamin D. Yet, it is seen that the African Americans, possessing a darker skin, despite having a lower level of vitamin D than required, develop fewer osteoporotic fractures compared with the Caucasians (Eisman, 1988).

People with fat malabsorption:

Fat solubility of vitamin D demands a little fat in the diet to be absorbed well in the gut. Individuals having decreased vitamin D absorption capability need the its supplementation in order to meet its demands. Some of the diseases leading to fat malabsorption include:

Liver diseases Cystic fibrosis and Obese people:

            Obese people also come under at risk individual’s group for vitamin D inadequacy. This is thought to be true for people with a BMI > 30. As their obesity increases, the level of vitamin D in their body decreases. This is because of an increase in the body fat. The reason behind is greater amount of subcutaneous fat sequester more of the vitamin and affect its release in to the circulation. BMI is inversely related with the peak serum concentrations of vitamin D, thus sometimes even the oral supplementation in such individuals causes sequestration of the vitamin into the larger fat pools of the body.

People with gastric bypass surgery:

Such individuals are prone to develop a deficiency of vitamin D because part of upper small intestine, where vitamin D gets absorbed is bypassed. Thus, they also require the oral supplementation of vitamin D.

Older adults:

            Older adults come under the endangered groups in case of developing deficiency of vitamin D; because, with an increasing age, the skin loses its ability to synthesize vitamin D from sunlight. Also, there becomes a decreased ability to convert vitamin D in kidneys into live hormone.

Conclusion

Initially it was thought vitamin D is imperative only for preventing rickets in children or osteomalacia in adults or osteoporosis in elderly group or is responsible for bone health but now it is established fact that vitamin D is imperative for metabolic processes. Deficiency of vitamin D and reduced solar UVB exposure increases the risk of various widespread cancers or type I diabetes, various autoimmune disorders like multiple sclerosis and rheumatoid arthritis and schizophrenia. Various studies demonstrate that vitamin D has evolved as a vital and necessary hormone, which acts as a marker for the overall health and well being of an individual. It is therefore important to maintain normal vitamin D level of 75-125nmol/L. It is therefore mandatory that one must get the plasma levels of 25(OH)D checked and it should be part of routine checkups. 

References

Cantorna, MT, Munsick, C, Bemiss, C, Mahon, BD., 2000. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr, 130, 2648–52. Davidsons, 2002. Principles and Practice of Medicine, 19th Edition, Churchill Livingstone. DeLuca, HF., 2004. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr, 80, 1689S–96S. Eisman, JA., 1988. “Osteomalacia”. Baillières Clin Endocrinol Metab 2 (1), 125–5 Garland, CF., Garland , FC., Gorham, ED., 1993. Rising trends in melanoma. An Hypothesis concerning sunscreen effectiveness. Ann Epidemio,. 3(4),451. Goldman, A., 2004. Cecil Textbook of Medicine, 22nd edition. Volume 2. Saunders: An Imprint of Elsvier. Grant, WB. 2002. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer, 94,1867–75. Grodstein, F, Speizer, FE, Hunter, DJ., 1995. A prospective study of incident squamous cell carcinoma of the skin in the Nurses’ Health Study. J Natl Cancer Inst, 87:10616. Holick, MF., 1998. Clinical efficacy of 1,25-dihydroxyvitamin D3 and its analogues in the treatment of psoriasis. Retinoids, 14, 12–7. Holick, MF., 1999. ed. Vitamin D: physiology, molecular biology, and clinical applications. Totowa, NJ: Humana Press, 109–28. Holick, MF., 2004. Vitamin D: importance in the prevention of cancers, type 1diabetes, heart disease, and osteoporosis. Am J Clin Nutr, 79, 362–71. Holick, MF, 2006. The role of vitamin D for bone health and fracture prevention Current Osteoprors. Rep, 4(3), 96-102. Kennedy, C., Bajdik, CD., Willemze, R., de Gruijl, FR., Bavinck, JN., 2003. The influence of painful sunburns and lifetime of sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi and skin cancer. J Invest Dermatol, 120, 1087–93. Lapp, JL., 2009. Vitamin D: Bone Health and Beyond. American Journal of Lifestyle Medicine, Vol. 3 (5), 386-393. Lee, S, Clark, SA, Gill, RK, Christakos, S., 1994. 1,25-Dihydroxyvitamin D3 and pancreatic ß-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology, 134:1602–10 Lips. P., Bouillon, R., Van Schoor, NM., Vanderschueren, S., Kuchuk, N., Milisen, K., Boonen, S., Reducing fracture risk with calcium and vitamin D. [Online] 2009 [cited October 15th, 2009]. Available from:

17.Kreiter, SR., Schwartz, RP., Kirkman, HN., Charlon, PA., Calikoglu, AS., Davenport, ML., 2000. Nutritional rickets in African-American breast-fed infants. J Pediatr, 137, 153–7.

18. Nesby-O’Dell, S., Scanlon, KS., Cogswell, ME., et al., 1988-1994. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, Am J Clin Nutr, 76, 187–92.

20. Tanaka, H., Abe, E., Miyaura, C., et al. 1982. 1,25-Dihydroxycholeciferol and human myeloid leukemia cell line (HL-60): the presence of cytosol receptor and induction of differentiation. Biochem J, 204, 713–9.

22. Tsoukas, CD., Provvedine, DM., Manolagas, SC., 1984. 1,25-Dihydroxyvitamin D3, a novel immuno-regualtory hormone. Science, 221, 1438–40.

23. Veierod, MB., Weiderpass, E., Thorn, M., et al. 2003. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 95:1530–8.

24. Weishaar, RE., Simpson, RU., 1987. Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects. Am J Physiol,

Conclusions and Implications:

The role of histamine in mental illness has been theorized about for several decades, but both the conventional and alternative medical fields have been very slow to respect histamine’s influence in mental health. In addition, the vast majority of conventional and alternative practitioners do not realize that vitamin C has potent antihistamine effects, which can be beneficial in both physical and mental health. Conventional medicine uses pharmaceutical antihistamines to treat histamine-related physical complaints, and sometimes mental ones as well. As mentioned earlier, pharmaceutical antihistamines have several side effects, including many that worsen mental health. It is lamentable that the vast majority of alternative practitioners are ignorant of vitamin C’s antihistamine effects. It is the purpose of this dissertation to convey vitamin C’s antihistamine effects, especially as it pertains to treating various forms of mental illness.

The evidence for vitamin C’s positive impact on mental health is compelling. Vitamin C can act as a mild antidepressant via boosting cAMP levels. Low cAMP levels are associated with depression. Vitamin C also helps produce norepinephrine, which, like cAMP, is often low in depression. In fact, cAMP is downstream of the norepinephrine pathway, which is the pathway that many pharmaceutical antidepressants use to boost mood. Vitamin C also hydroxylates dopamine to help form norepinephrine (Goodman, et al., 1996).

Vitamin C, when used in large doses, can potentially reduce anxiety (Balch & Balch, 1997). As mentioned previously, the brain constantly strives to keep the vitamin C levels constant, no matter how low the levels are in the rest of the body. So, the question arises: how can low or high vitamin C levels affect mental health, assuming that it is at a constant concentration in the brain? A plausible explanation is the following: the total vitamin C pool in the body may become more oxidized than reduced. Recall that only oxidized vitamin C enters the brain, where it is then reduced. If there are not sufficient reducing agents in the brain, then the vitamin C will remain oxidized, and therefore most of its properties rendered useless. Reduced vitamin C modulates dopamine levels in the brain, and can thus act as a natural antipsychotic by lowering high dopamine levels. It also helps secrete oxytocin, a pleasure hormone, thus improving mood. As mentioned previously, “ascorbate promotes myelin formation” (Rice, 2000, p. 214). Vitamin C also inhibits release of the stress hormone cortisol, which in excess for prolonged periods can precipitate depression. It also helps protect the brain from drug-induced neurotoxicity, presumably by its antioxidant effects.

However, by far the most important positive effect on mental health that vitamin C has is its antihistamine effect. This is because, as mentioned before, histamine has several detrimental effects on mental health. Administration of histamine into animal brains reinforced fear memory (Blandina, et al., 2004). It is well known that histamine plays a major role in allergic reactions, and allergic people are significantly more likely to suffer from depression (Firshein, 1996; Ossofsky, 1976). Histamine itself can directly cause behavioral depression (Arrigo-Reina & Chiechio, 1998).

As mentioned previously, histamine either directly or indirectly influences all other major neurotransmitters, often via inhibition of neurotransmitter release (Brown, Stevens, & Haas, 2001), thus theoretically causing anxiety, depression, or both. The anxiety may be caused by histamine’s inhibition of GABA, which slows nerve transmission. The depression may be caused by inhibition of the ‘antidepressant’ neurotransmitters serotonin and norepinephrine. However, histamine can also release norepinephrine (Bugajski, 1984), thus potentially causing anxiety or mania. Stress often releases histamine, which in turn will help release the HPA axis stress hormones. It is known that chronic HPA activation is associated with depression and brain alterations. There is also evidence that histamine activates the calcium pathway more than the DAG pathway (Sarri, Picatoste, & Claro, 1995). There is abundant evidence that the DAG pathway is antidepressant-like, and the calcium pathway may cause depression.

Besides its antihistamine effect, there are multiple sources of evidence to suggest that humans should supplement with vitamin C. Dr. Linus Pauling, a two-time Nobel Prize winner, believes that adult humans need between two to nine grams of vitamin C daily (Haas, 1992). Animals who can synthesize vitamin C do so at 45-300 times the adult human RDA, which is about 0.9 mg/kg/day (60-90 mg/day) (Levine, 1985). For a 150 pound human, this would extrapolate to about 12 grams per day, if humans synthesized their own vitamin C. Vitamin C blood and tissue levels decline with age (Lieberman & Bruning, 1997), which is an additional reason to supplement. If vitamin C is taken as a supplement, then other supplementation should be considered, since vitamin C needs calcium, magnesium, and bioflavonoids to help its own assimilation (Balch & Balch, 1997).

Recommendations for Further Research:

Since vitamin C and histamine are involved in both physical and mental processes, this leads to the question of psychosomatic issues with both molecules. Recall that both molecules are also involved in the immune response and pro- or anti-allergic responses. There are three possible links between psychic state and somatic allergy. First is that allergies are produced by psychological stress. Second is that psychological stress is produced by allergies. Third is that allergic exposure can produce both psychic and somatic responses. This third link has been proven in a double-blind study (King, 1981). As mentioned earlier, allergy-mediated histamine release is associated with various mental reactions.

There have been various theories on the molecular basis of mental illness for several decades. The first theory is called the monoamine theory, formed in the 1950’s and 1960’s. It proposes that abnormal brain function is directly dependent on fluctuating monoamine levels (serotonin, norepinephrine, dopamine, GABA). Interestingly, histamine was not included in the original monoamine theory, probably due to the lack of research at the time regarding its mental health effects. At that time, doctors would most often give only antidepressants to depressed patients, and benzodiazepins (ex. Xanax, Valium) to anxious people. The second theory is the comorbid theory, which dominated psychiatric philosophy in the 1990’s. It was formed after the realization that drugs such as Prozac could singlehandedly reduce both depression and anxiety. The third is the subsyndromal theory, which evolved from the discovery that the vast majority of anxious people have some depression, and vice versa. The philosophy of the subsyndromal theory is basically in-between the monoamine and comorbid theories.

The discovery that histamine can inhibit all other major neurotransmitters suggests taking another look at the original monoamine hypothesis of mental illness. It is known that dopamine tends to be high in psychosis, norepinephrine high in mania, and serotonin low in depression. It could be postulated that psychotics have a dopaminergic-dominated neurotransmitter system, bipolars a norepinephrine-dominated neurotransmitter system, and depressives a serotonin-dominated neurotransmitter system. The fourth major monoamine, histamine, may very well be dominant in atopic (allergic) people. People with histaminergic-dominant neurotransmitter systems could have a very wide variety of mental illnesses, since histamine affects the release of all major neurotransmitters. The biochemical characterization of the histaminergic person may therefore be of interest to practitioners in order to help that person physically and mentally. This characterization leads to the topic of metabolic typing, described below.

In the emerging nutritional science of metabolic typing, people are asked a series of questions to determine what type of biochemistry they have. Some people are slow oxidizers and tend to be sympathetic nervous system dominants. Those people do better on carbohydrates. Others are fast oxidizers and tend to be parasympathetic nervous system dominants. These people do better with more fat and protein in their diet. Too many carbohydrates for a fast oxidizer can bring a lot of physical and mental problems. Since histamine is a stimulatory molecule, it may hasten oxidation, and histaminergic types may want to consider limiting carbohydrates.

There is some evidence to suggest that histamine is involved in creating the parasympathetic dominant biochemistry in a person. The parasympathetic branch of the CNS is responsible for decreased heart rate and increased digestive secretions, both of which are also caused by histamine release. Also, physical tendencies of parasympathetic dominants include allergies and excessive appetite (Wolcott & Fahey, 2002). Histamine is a major cause of allergies and its stimulatory effect on digestion can result in excessive appetite.

Besides its antihistamine effect, vitamin C can help a person’s biochemistry in other, more subtle ways. Vitamin C can be purchased as straight ascorbic acid, or the pH neutral calcium ascorbate or sodium ascorbate. For people who are sympathetic dominants, straight ascorbic acid should be tried, since those types of people may not have sufficient hydrochloric acid secretions. The loosely bound hydrogen from the ascorbic acids hydroxyl group will dissociate in the stomach and help digest protein. Ascorbic acid may also be helpful to balance the blood pH of people with metabolic alkalosis.

Conversely, parasympathetics, who tend to have robust hydrochloric acid production, should try calcium ascorbate, since the ascorbate will accept excess hydrogen ions in the stomach. Calcium ascorbate taken in large doses may help neutralize acid reflux. Calcium is also good for parasympathetics, since it slows down oxidation (Wolcott and Fahey, 2002). Calcium ascorbate may help balance the blood pH of people who have metabolic acidosis.

Other future research may concentrate on how megadosing with vitamin C affects mental health quantitatively. There has already been research proving that vitamin C intake enhances mood (Brody, 2002; Balch & Balch, 1997). So far, there has not been a large study to see if vitamin C alone can significantly reduce depression or anxiety, either in conventional or alternative medicine. There are two main clinical scales to measure depression and anxiety—the Hamilton depression scale and the Hamilton anxiety scale. It would be of interest to see if vitamin C alone could significantly reduce depression and/or anxiety.

Since different people have different biochemistry, the question arises of how much vitamin C is needed daily by a person for physical and mental health. One of the best ways to test how much vitamin C a person needs is to have them do an ascorbic acid flush. This can be done with both ascorbic acid and calcium/sodium ascorbate. The protocol can be varied, but it usually consists of a person taking 1-2 grams of vitamin C every hour until bowel tolerance occurs (diarrhea). The grams of vitamin C are counted and recorded. The final gram(s) that cause bowel tolerance are usually multiplied by 50-80%, and that is the baseline daily dose that the person should take from then on. For example, if 18 grams causes bowel tolerance, than 9-16 grams is the daily baseline amount. If the person is under an unusual amount of stress, or has a viral infection, the baseline can be raised until bowel tolerance occurs at a higher level than before. Again, the new temporary bowel tolerance is lowered a certain percentage until the stressor abates.

Summary:

The contents of this dissertation have introduced a multidimensional model for the attenuation of histamine-related mental illness via vitamin C supplementation. Both histamine and vitamin C affect the human body on multiple levels. Histamine plays many different roles in the body, including neuromodulation, neurotransmission, allergic mediator, inflammatory mediator, and gastric acid secretion stimulator. When histamine levels are in the normal range, the above processes are usually in equilibrium and functioning optimally. It is when histamine levels become too low or high that trouble can arise. One of the roles of vitamin C in the body is to modulate histamine levels; if histamine levels are low, vitamin C administration will cause small amounts of histamine to be released. When histamine levels are abnormally high, vitamin C acts as an antihistamine, destroying excess histamine and thus bringing this chemical down to normal physiological levels.

In addition to its antihistamine effect, vitamin C has many other actions on the body. Like histamine, vitamin C is also both a neuromodulator and an immunomodulator. In fact, based on the information earlier in this dissertation, it is not an exaggeration to state that vitamin C is histamine’s counterpart and molecular ‘watchdog’. Unfortunately for humans, vitamin C cannot be synthesized in the body, so it must be supplemented either in food or nutritional supplements. If humans could synthesize vitamin C, a 150 pound person would make roughly 12 grams of vitamin C daily. That’s 133-200 times the US RDA (recommended daily allowance) of vitamin C. This statistic underscores the fact that there is a huge difference between the RDA of vitamin C designed to prevent rare diseases, and the optimal amount to sustain physical and mental health.

Sub-optimal amounts of vitamin C in the blood and tissues can allow histamine to rise to dangerous levels. Histamine competes with other neurotransmitters, and excess histamine can end up dominating and inhibiting other neurotransmitters. This can lead to anxiety and/or depression. Histamine sometimes releases norepinephrine and dopamine, and these two neurotransmitters in excess can precipitate mania and psychosis, respectively. Histamine may also be involved in ADD (Passani, Bacciottini, Mannaioni, & Blandina, 2000). Stress releases histamine, which then in turn releases various stress hormones that can result in serious bodily harm if the stress is chronic. Just as histamine dominates other neurotransmitters, it also can deregulate the HPA axis by overstimulation of the pituitary and adrenal glands.

The molecule cyclic AMP (cAMP) is an extremely important regulator of metabolism. Robust levels allow the maintenance of both physical and mental health. Low levels can result in asthma, depression, and possibly even cancer. Histamine lowers cAMP levels, by a mechanism that is not completely elucidated; it may have to do with the calcium pathway antagonizing the cAMP pathway. Vitamin C boosts cAMP levels by at least three methods: directly degrading histamine, synergism with cAMP producers, and inhibiting the enzyme (phosphodiesterase) that degrades cAMP. In this way it can attenuate, prevent, or even reverse asthma, depression, and cancer. Vitamin C also helps reverse asthma by slowing down synthesis of the inflammatory mediators arachidonic acid (AA) and PGF2a. cAMP also inhibits histamine release (Mohsenin & Dubois, 1987).

It has been shown in this dissertation that vitamin C is very beneficial for mental health in many different ways. Vitamin C benefits mental health both with its antihistamine effects and in numerous other ways as well. It is very unfortunate that humans cannot synthesize their own vitamin C. Animals who synthesize their own vitamin C develop cancer much less than humans. Yet the RDA for vitamin C is a paltry 60-90 mg/day, just enough to prevent certain diseases that are very rare in developed countries. The time will come when vitamin C is recommended by both doctors and nutritionists in doses that are appropriate to a person’s weight—about eight grams for every 100 pounds, as suggested by the two-time Nobel Prize winner Linus Pauling.

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