Vitamin deficiency is very common. Here’s what your patients are most likely lacking

Vitamin supplementation could prove clinically useful

The average American eats 10 pounds of chemical additives and 200 pounds of sugar each year. About 50% of the diet consists of refined carbohydrates. Even though medicine does not recognize subclinical vitamin deficiency, it exists. Supplementation is often helpful. Here are some supplements you may find clinically useful. 

Vitamin B6

Vitamin B6 in coenzyme form performs a wide variety of functions in the body and is extremely versatile, with involvement in more than 100 enzyme reactions, mostly those concerned with protein metabolism.¹  

According to the NIH, isolated B6 deficiency is uncommon. However, vitamin B6 deficiency is found in conjunction with deficiencies of other B vitamins, like thiamin. In certain patients, B6 deficiency can be found. Consider it for patients with low kidney function and for those with autoimmune diseases.² People who have kidney disease or conditions preventing the small intestine from absorbing nutrients from foods (malabsorption syndromes) are more likely to be vitamin B6 deficient. Some epilepsy medications and alcohol dependence also can lead to vitamin B6 deficiency. Deficiency can cause anemia, confusion, depression and a weakened immune system. 

Vitamin B6 status is of concern because of homocysteine, but the link to poor B6 status and inflammation may go beyond that.^3-4 PLP concentrations were inversely correlated with the levels of two markers of systemic inflammation, C-reactive protein (CRP) and fibrinogen.⁶ The analysis of inflammation markers in 2,686 participants of the U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004 indicated serum CRP concentrations were inversely related to total vitamin B6 intake (from both food and supplements). 

In a case-control study that included 267 patients with coronary artery disease and 475 healthy controls, plasma PLP concentrations were inversely correlated with the levels of two markers of systemic inflammation, C-reactive protein (CRP) and fibrinogen. Yet, the study suggested suboptimal PLP levels (<36.3 nanomoles/liter) might contribute to an increased risk of coronary artery disease independently of inflammation since the risk was unchanged after adjustment for inflammation markers. In other words, poor B6 status is a risk factor for coronary artery disease independent of inflammation. 

While everyone focuses on homocysteine when discussing B6 and cardiovascular health, it may be useful to discuss taurine. Vitamin B6 is a cofactor for cysteine to be converted to taurine. Taurine has been researched and found to be beneficial for lowering blood pressure and for improving lipid profiles.^7-9 

Vitamin B6 plays a role in hemoglobin production. It is especially effective for women of childbearing age.^10-11 It is not uncommon for a patient to be given iron when in reality, they need B6. 

There are several studies supporting the use of vitamin B6 for patients with PMS. A three-month study in more than 60 premenopausal women found that taking 50 mg of vitamin B6 daily improved the PMS symptoms of depression, irritability and fatigue by 69%.¹² Another study looked at 630 women and a much higher dose of B6. They had daily doses of pyridoxine hydrochloride varying from 40 to 100 mg early in the study and from 120 to 200 mg in the later period of the investigations. The response to treatment was recorded as good (no significant residual complaints) in 40% or more of patients taking 100-150 mg pyridoxine daily and in 60% of patients treated with 160-200 mg daily.¹³   

Depression and anxiety can be caused by inadequate B6. B6 is a necessary cofactor for reactions producing two major neurotransmitters: serotonin from the amino acid tryptophan and dopamine from L-3,4-dihydroxyphenylalanine (L-Dopa). Other neurotransmitters, including glycine, D-serine, glutamate, histamine and γ-aminobutyric acid (GABA), are also synthesized in reactions catalyzed by B6-dependent enzymes. 

Vitamin B9

Folate or vitamin B9 gets its name from the Latin word folium, meaning leaf (think of the word foliage). Green leafy vegetables are the source for folate. It is necessary for the production of blood cells, and folate deficiency can lead to megaloblastic anemia. It is in all prenatal vitamins because it helps prevent neural tube defects. Adequate folate consumption may affect the frequency of migraines in some patients.¹⁴ 

Folate is necessary for cell reproduction, especially cells that turn over frequently. It is important for homocysteine metabolism. It, plus vitamins B12 and B6, are necessary to keep homocysteine low. Homocysteine and low folate levels may play a role in cervical dysplasia, which may be prevented (or even treated) with folate supplementation.^15-17 The cells of the small intestine turn over frequently, and in some cases, folate can bring diarrhea under control because these cells have a need for it. It may even help you address cases of IBS with diarrhea. 

There may be a cancer link for low folate as well. In one study, RBC folate levels were significantly lower in pancreatic cancer cases compared to unrelated controls.18 It may play a role in preventing cancer in general.^19-21  

The role folate plays in keeping homocysteine in check may make it useful for patients with depression. Studies have linked high homocysteine levels to depression.^22-23 High homocysteine is a source of inflammation. Studies are showing inflammation, in general, is linked to depression.^24-27 Reducing inflammation can also improve cognition.²⁸   

Vitamin B12

Vitamin B12 is necessary for normal metabolism of nerve tissue and is involved in protein, fat and carbohydrate metabolism. B12 aids folate in the synthesis of choline. It helps the placement of vitamin A into body tissues. If a patient is taking metformin, they need B12 because the drug depletes the nutrient. 

B12 is poorly absorbed unless intrinsic factor, a mucoprotein secreted in the stomach, is present. Autoimmune reactions in the body can bind intrinsic factor or can affect the cells that produce it. Absorption of B12 appears to decrease with age, and with iron, calcium and B6 deficiencies. Absorption increases during pregnancy. Testing for serum cobalamin may not be the best way to check for a B12 deficiency. Research found elevated homocysteine and elevated methylmalonic acid occurred in 95% of patients with cobalamin deficiency, whereas only 69% of these patients demonstrated a low serum cobalamin.29 A dozen of the subjects had symptoms of B12 deficiency, but serum cobalamin was higher than 200 pg/ml. The authors of the study concluded that measuring homocysteine or methylmalonic acid is a much better way to determine B12 levels than serum cobalamin. 

Vitamin B12 levels tend to decrease with age; this was verified by research.³⁰ Many problems with depression, cognition or other mental issues experienced by the elderly may be due to vitamin B12 or folic acid deficiency. One study looked at 296 elderly patients diagnosed with mental disease. Serum folate, homocysteine and cobalamin were measured. Over 7% of these patients had normal serum cobalamin levels, but high homocysteine. Treatment of these patients with vitamin B12 injections reduced homocysteine levels. Addition of folic acid to the treatment also lowered homocysteine in patients with low folate.³¹   

One study looked at the connection between vitamin B12 deficiency and the health of elderly patients.³² Out of 827 patients averaging 77 years of age (none younger than 60), 19.7% were vitamin B12 deficient. Vitamin B12 deficiency was associated with many health problems, including neurological symptoms like unsteadiness in the dark, Parkinsonism and hypopallesthesia. There were higher rates of diabetes, heart disease, cerebral ischemia, high blood pressure and gastrointestinal diseases in the vitamin B12 deficient group. Severe vitamin B12 deficiency can lead to pernicious anemia, which is a megaloblastic (large red blood cells) anemia. Neurologic symptoms show up in vitamin B12 deficiency long before the anemia develops. Of the deficient patients in this group, only 9.8% had a megaloblastic anemia. 

Vitamin B12 does seem to help with cognitive function. A small pilot study looked at 22 subjects with low serum B12 levels in conjunction with cognitive dysfunction.³³ The subjects received B12 injections (1000 milligrams) daily for one week, weekly for four weeks, then monthly for a period of six months. At the beginning of the study and after at least six months of therapy, the subjects were evaluated with the Mattis Dementia Rating Scale. Of the 18 patients who finished the study, 11 showed improvement. The amount of improvement experienced by the subjects correlated with the amount of time they had exhibited symptoms. The authors of this study believe there is a narrow window of opportunity to treat patients with cognitive problems due to vitamin B12 deficiency and that elderly patients should be regularly screened. 

There is a tendency to think that B12 must be given by injection because it is in a lot of foods and deficiency is largely due to problems with absorption. This has been studied and it has been found that a high dose (2 mg/day or more) works.³⁴  

Is it Alzheimer’s or is it B12 deficiency?

Mark Goodman, PhD, has some interesting observations about patients diagnosed with Alzheimer’s disease. He believes many patients diagnosed with Alzheimer’s actually have dementia caused by a lack of vitamin B12. Goodman has an accredited PhD in behavioral medicine (with a specialization in clinical neuropsychology) from the University of Maryland School of Medicine. Behavioral medicine is a new interdisciplinary specialty combining cross-training in behavioral psychology, neurosciences, physiology and medicine.   

Goodman is quoted in an interview by Kirk Hamilton that appeared in Clinical Pearls. Goodman says, “I initially suspected vitamin B12 limits were too low, when I encountered on consultation, geriatric patients admitted with Alzheimer’s diagnosis whose frontal lobe functioning was obviously intact. This is inconsistent with Alzheimer’s diagnosis. They were exhibiting other global neuropsychological deficits with a systemic/metabolic profile. They were all following cardiac lipid-lowering diets.” 

Goodman went on to say he believed many elderly individuals are subclinically B12 deficient. These patients often have normal blood levels of B12. He points out people who are B12 deficient experience neurological changes before there are changes in their blood count (pernicious anemia). 

Goodman says a good dietary history is an important part of the evaluation. If patients are on very high-starch diets like those occurring in many convalescent facilities, then there is a high suspicion of vitamin B12 depletion and deficiency. Goodman says, “In the convalescent facility diet there is little red meat due to expense and the desire to have residents on a lipid lowering regime. Also, there is a normal increase in gastric atrophy in the elderly which reduces vitamin B12 absorption. Thirdly, there is a down-regulation of the enzymes required for the formation and the manufacture of vitamin B12 when less vitamin B12 is consumed.” Goodman points out if there is no frontal lobe degeneration, the dementia is not Alzheimer’s disease. Goodman says that high doses of vitamin B12 are without any serious adverse side-effects.   

Vitamin B12 deficiency is fairly common in older people. Even when the tests for B12 levels are normal, symptoms like forgetfulness, fatigue and depression respond to B12 supplementation. Goodman’s point is the symptoms of this deficiency can be so severe the patient is often diagnosed with Alzheimer’s disease — even when the blood tests show normal levels of B12.  

PAUL VARNAS, DC, DACBN, is a graduate of the National College of Chiropractic and has had a functional medicine practice for 34 years. He is the author of several books and has taught nutrition at the National University of Health Sciences. For a free PDF of “Instantly Have a Functional Medicine Practice” or a patient handout on the anti-inflammatory diet, email him at paulgvarnas@gmail.com.

References

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3. Morris MS, Sakakeeny L, Jacques PF, Picciano MF, Selhub J. Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr. 2010;140(1):103-110.  
4. Sakakeeny L, Roubenoff R, Obin M, et al. Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults. J Nutr. 2012;142(7):1280-1285.  
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8. Hypertension. 2016 Mar;67(3):541-9 Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study 
9. Curr Hypertens Rep. 2018 Jul 13;20(9):81 The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis 
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24. J Clin Psychiatry. 2004 Aug;65(8):1090-5. Elevated circulating homocysteine and high-sensitivity C-reactive protein jointly predicts post-stroke depression among Chinese patients with acute ischemic stroke 
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27. Brain Behav Immun. 2014 Jan;35:70-6. The association between depressive symptoms, cognitive function, and inflammation in major depression 
28. Clinical Nutrition (2006; 25(1): 60-7) Vitamin B12 and folate serum levels in newly admitted psychiatric patients 
29. American Journal of Hematology (1990;34:99-107) Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations 
30. Archives of Family Medicine (October 1994;3:918-922). 
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