PHOENIX—When it comes to managing a broad range of common chronic conditions and quickly improving patients’ overall sense of wellbeing, few things pack as much therapeutic punch as the B vitamins, said Sara Thyr, ND, at the annual meeting of the American Association of Naturopathic Physicians.

Safe, inexpensive, and fast-acting, B vitamins can make a profound difference in the lives of people with chronic fatigue, anxiety, hepatic disorders, infertility, arthritis/joint pain, and a host of other common disorders.

“When I was in medical school, they said, ‘You can’t ever go wrong by treating the liver.’ I’ve learned over the years that you can never go wrong by looking for and treating B vitamin deficiencies. Often the two (B vitamin deficiency and hepatic problems) go hand in hand,” said Dr. Thyr, who practices naturopathic primary care in Nashua, NH. “I started to see so many interesting things happening in my practice once I started using B vitamins regularly, that it has become a passion for me. My friends have started calling me ‘Queen B.'”

Deficiency Is Common

Assessment for B vitamin deficiencies has become a basic part of Dr. Thyr’s standard evaluation. While extreme, life-threatening deficiencies such as beriberi are rare in this country, many people have very low dietary intake and consequently, suboptimal blood and tissue levels. Further, many common drugs deplete B vitamins (see table). “Whenever possible, try to get patients off B-depleting drugs,” Dr. Thyr advised.

Given the key roles these nutrients play in basic metabolic processes, hepatic detoxification pathways, neuronal myelinization, steroid hormone production, regulation of blood sugar, and neurotransmitter synthesis, correcting deficiencies will have simultaneous benefits for a number of different organ systems. In a sense, B vitamins provide a holistic, multi-system tool for treating several different co-morbid conditions at once.

Increasing daily dietary intake of B’s is always a good idea, but in a therapeutic context more intensive measures like intravenous injection are usually necessary. “I do a lot of IV pushes for patients with deficiencies. Oral dosing does work, but it is slower.”

The B vitamin family represents a number of different compounds, all of which are essential for health. While patients who are deficient in one will likely be deficient in others, you will be most able to maximize the benefit of B vitamin therapy if you understand how each compound functions, how specific deficiencies manifest clinically, and how best to correct the problems. Dr. Thyr offered the following guide to the B vitamin line-up.

Vitamin B1 (Thiamine)

Thiamine pyrophosphate is an essential coenzyme for all Krebs cycle reactions, putting it at the core of the cellular metabolic engine. It is vital for healthy nerve function because it is essential for myelinization. It is also involved in the production of acetylcholine.

Extreme deficiency (beriberi) manifests as anorexia, cardiomyopathy and paresthesias. Fortunately this is rare in the US. Less severe deficiencies, however, are widespread and growing. “There’s a lot of B1 deficiency these days because people are going on low-carb diets, and many Americans were getting thiamine primarily from enriched flour,” said Dr. Thyr. This is exacerbated by our national love of caffeine. Coffee and tea are both diuretics, and tend to wash out water-soluble vitamins like B1.

B1 deficiency manifests as cardiac abnormalities, neuromuscular problems, numbness, tingling, cognitive dysfunction and “foggyheadedness.” You can practically assume B1 deficiency in any patient with frequent or acute diarrhea. Chronic stress also depletes this vitamin.

The best food sources of B1 are chicken, tuna, sunflower seeds, black beans, whole grains (like brown rice), and lentils. The current RDA for B1 is 1.4 mg, a number Dr. Thyr believes is far too low. “It is very safe. Even at daily doses of 500 mg, there’s low toxicity. In fact, the National Academy of Sciences has not even established a tolerable upper limit. The only potential adverse reaction is local inflammatory reactions at the site of intramuscular injection.”

Vitamin B2 (Riboflavin)

Riboflavin plays a central role in cellular oxidation/reduction reactions in all tissues in the body. It is involved in processing iron (Ferritin) for heme synthesis, and it is critical for maintaining erythrocyte integrity. Riboflavin deficiency manifests most commonly as cheilosis, stomatits, glossitis, sore throat, keratitis, neuropathy, and seborrheic dermatitis. Deficiency is especially common in alcoholics and in people with HIV, malignancies, or liver diseases.

Riboflavin is found in Crimini mushrooms, calf liver, spinach, lettuce, spelt flour, asparagus, chard, cauliflower, broccoli, sunflower seeds, and raw tomatoes. When supplementing, riboflavin is safe in doses up to 400 mg per day. Above that level, some patients may experience diarrhea or polyuria. The 400 mg dose is the recommended level for treating migraine headaches. Though it is not clear that migraines are a sign of riboflavin deficiency, many migraine patients will be deficient, and there is evidence that riboflavin can reduce migraine frequency.

Riboflavin is the vitamin that gives the yellow-orange cast to the urine of people taking supplements. If a patient is not a veteran supplement-taker, it is a good idea to let him/her know about this; some patients find the phenomenon a bit alarming if they are not expecting it.

Vitamin B3 (Niacin)

The term “niacin” is used more or less synonymously for both niacinamide (nicotinamide) and nicotinic acid, though technically it should only refer to the latter. Nicotinic acid was first isolated in the 1930’s, from tobacco, and was found to be an effective treatment for Pellagra, which manifests as dry, scaly skin, digestive problems, and overall weakness/fatigue.

Like others in the B family, B3 plays multiple biochemical roles. It is an essential player in metabolism of fat, carbohydrates and protein. It is the building block for NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). It promotes storage of energy in muscle and the liver, while also regulating insulin sensitivity and glucose metabolism. In fact, it is proving very important for managing diabetes. Dr. Thyr cited evidence that it can prevent autoimmune destruction of islet cells.

Niacin also has multiple vascular effects. It induces vasodilation and promotes peripheral vascular circulation. It lowers LDL while increasing HDL, thus improving lipid profiles in patients at risk for cardiovascular disease.

Deficiency is common in patients with chronic diarrhea and irritable bowel syndrome, as well as those facing constant stress. Oral contraceptives and excess alcohol consumption deplete niacin.

Niacin-rich foods include Crimini mushrooms, Yellowfin tuna, chicken, Chinook salmon, Halibut, and asparagus. Some strict vegetarians are niacin deficient, and this usually reflects a low intake of tryptophan, which normally converts to niacin when present at sufficient concentrations. However, this conversion process involves vitamin B1 and B6, so people deficient in those two will sooner or later become deficient in B3, and increasing tryptophan-containing foods won’t really help unless these other deficiencies are also corrected.

Given its vasodilatory effect, flushing is a very common effect from niacin supplements. This bothers some people more than others. For those who cannot tolerate the flushing, a sustained release formulation is a good option. Many clinicians advocate inositol hexaniacinate as a no-flush alternative to nicotinic acid. However, there is no research yet to demonstrate physiologic equivalence. All studies showing cardiovascular benefits from niacin have been done with nicotinic acid.

Niacinamide and niacin (nicotinic acid), though biochemically equivalent, have different physiologic effects. “You can often distinguish the two by their side effects,” said Dr. Thyr. At high doses, niacin causes tingling, burning, flushing, intracranial blood flow, hypotension, tachycardia, arrhythmias. High-dose niacinamide causes nausea, vomiting, diarrhea, headache, dizziness, blurred vision, hepatotoxicity and hyperglycemia.

Vitamin B5 (Pantothenic Acid)

Pantothenic acid is involved in metabolism of carbohydrates, protein and fats, and serves as a precursor to Coenzyme A, required for acetylation reactions during gluconeogenesis. It is involved in synthesis and degradation of fatty acids, and synthesis of steroid hormones and neurotransmitters.

This member of the B family is particularly important for healthy function of the adrenal gland; it can be very helpful for patients under a lot of stress.

B5 deficiency manifests as fatigue, numbness, sensations of tingling or burning in the feet, and general weakness. It is especially common in people with celiac disease or digestive function problems. Be aware that antibiotics can sometimes induce B5 deficiency, because they kill off the normal flora that play a role in intestinal absorption of this vitamin.

The natural form of pantothenic acid is present in a variety of fresh vegetables. However it is one of the least stable and most heat-sensitive of the B vitamins, so cooking, freezing, canning or other processing of vegetables tends to obliterate it.

In order to function properly, B5 requires adequate levels of B12, folic acid and biotin, a fact that underscores the inter-relatedness of these vitamins. Pantothenic acid can be given via injection, as Dexpanthanol, which is converted to active pantothenic acid by the body. Orally, it is very safe, and can be given at doses up to 10 grams per day without major adverse effects. Above 2 g per day, some patients will have diarrhea. Pantothenic acid is actually a very good natural remedy for constipation, Dr. Thyr said.

Vitamin B6 (Pyridoxine)

“This is probably my favorite B vitamin,” said Dr. Thyr. “It is involved in over 100 enzyme reactions, amino acid metabolism, fat and carbohydrate metabolism, heme synthesis, and the synthesis of GABA, serotonin, dopamine and norepinephrine. Deficiency can be very detrimental to a lot of physiology.”

She has found it to be effective for a wide variety of conditions, especially women’s health issues. “There’s nothing that improves pregnancy related nausea like a B6 injection.” Likewise, premenstrual syndrome patients respond very well; it can quickly resolve muscle cramps. “I’ve also seen improved conception rates in my infertile patients after giving them B6 injections.”

She’s had success treating eczema and seborrheic dermatitis, because B6 improves skin cell membrane integrity and function. It can also be used to prevent kidney stones, because it reduces urinary excretion of oxalate.

Depletions are commonly due to low dietary intake, but are exacerbated by a number of common drugs (see chart). Food sources include spinach, red bell peppers, turnip greens, garlic, cauliflower, mustard and collard greens, kale, asparagus, chard, Crimini mushrooms, bananas, celery, cabbage, Yellowfin tuna, and cod.

Vitamin B6 is available in 2 forms: pyridoxine HCl, and pyridoxal-5-phosphate, which is the activated form. Many supplement products contain both, which is good. This vitamin can make a world of difference for patients when given via injection. “I generally give 50–100 mg injections, though it is very well tolerated at doses up to 2 grams.” It is safe during pregnancy and lactation, and can be used in children in doses up to 30–40 mg per day.

Oral dosing depends on the main condition being treated. For women with deficiencies due to oral contraceptive use, Dr. Thyr generally gives 25–30 mg. For PMS, 50–100 mg is usually needed, along with magnesium. Prevention of kidney stones is best done with an oral combination of 300 mg magnesium plus 10 mg pyridoxine. For nausea during pregnancy, give 10–25 mg every 8 hours.

It is an excellent therapy for hereditary sideroblastic anemia; begin with doses in the range of 200–600 mg per day, and then taper down to 30–50 mg daily, once the patient begins to respond.

At very high doses, pyridoxine can cause sensory neuropathy, nausea, vomiting, abdominal pain, and loss of appetite. Be aware that it can enhance metabolism of levodopa (though not carbidopa). At daily doses in the range of 200 mg, it can also reduce plasma levels of phenobarbitol and phenytoin (dilantin), so carefully monitor patients taking any of these 3 drugs.

Vitamin B12

The term B12 covers 4 distinct compounds: adenosylcobalamin (found in meats), cyanocobalamin (the injectable form), hydroxycobalamin (also injectable), and methylcobalamin (intravenous form). Cobalamin is an important compound for myelin sheath synthesis, as well as for cell reproduction, normal erythropoiesis, and synthesis of methionine from homocysteine.

Deficiency shows up as depression, anxiety, menstrual problems, dandruff, difficulty swallowing, glossitis, and numbness/tingling sensations in the feet. Chronic deficiency can lead to growth problems in kids. “Watch for this in vegetarian families,” said Dr. Thyr. “Tofu and other vegetarian staple foods really do not have a lot of stable B12.” In general, there are few food sources beyond liver, meat and fish (snapper, salmon, shrimp, scallops, cod, halibut). “Blue-green algae are really the only reliable vegetarian source.”

She noted that two Nobel prizes have been won for work with B12, the first being in 1934, when liver was discovered to effectively resolve pernicious anemia, and the second in 1964, when the structure of cobalamin was identified.

Deficiency is common in people with inflammatory digestive disorders, and also those who are hypochlorhydric (do not produce adequate stomach acid). It can be depleted by a host of drugs, but be especially vigilant in patients taking H₂ blockers or proton pump inhibitors, antibiotics, metformin, and oral contraceptives. “Anything that reduces stomach acid will reduce B12.”

B12 is useful in treating anemia, hyperhomocysteinemia, disordered circadian rhythms, Imerslund-Grasback disease (a familial, hereditary, selective B12 absorption deficiency), and in stroke recovery. “Intranasal, sublingual, oral and intramuscular forms can all be helpful. Oral dosing is fine, so long as the patient has no absorption problems.”

Folic Acid

Folic acid is a catalyst in intracellular metabolism, and is a rate-limiting compound for DNA synthesis. This may be why it has proven so effective in preventing neural tube defects.

There is no question it can reduce elevated homocysteine, thought to be a risk factor for cardiovascular events. Last fall, reports from the NORVIT trial challenged the notion that folic acid can reduce CVD morbidity and mortality (see “New Data Challenge Homocysteine-CVD Connection” and “Is Homocysteine Dead?” at www.holisticprimarycare.net). Future studies will clarify the role of homocysteine in the management of heart disease. In the mean time, there are plenty of other reasons to make sure your patients maintain adequate folate levels.

Clinically, it can improve endothelial dysfunction, prevent nitroglycerine-induced nitrate tolerance and cross tolerance to endothelial nitric oxide. Epidemiologically, it seems to reduce the risk of breast, uterine, cervical and colon cancer. In practice, Dr. Thyr has found it highly effective for patients with depression, chronic fatigue, and interestingly enough, gingival disease.

Folate is found naturally in romaine lettuce, spinach, asparagus, turnip, mustard and collard greens, kelp and calf liver. In addition to the host of drugs that cause folate depletions, heavy alcohol use, excessive coffee drinking and smoking also reduce folate levels.

There are a variety of supplemental forms of folic acid, including natural folate, folicacin, pteroglutamic acid, pteromonoglutamic acid, and pteroglutamate. “Folate in food is actually less bioavailable than synthetic forms, which are 100% bioavailable. If you’re treating a folate-deficient patient, this is a rare instance to forego the general “food-source is better” rule, and opt for synthetics.”

For adults, including pregnant and lactating women, folic acid is very safe up to 1,000 mcg (1 mg) per day. Patients with celiac disease or megaloblastic anemia can actually tolerate up to 5 mg per day. At levels greater than 5 mg, it can cause abdominal cramps, rashes, and diarrhea. Push it up any further, and people may experience altered sleep patterns, excitability, abdominal distention, allergic skin reactions, nausea, and “crazy dreaming.” There’s no reason to ever go up that high, Dr. Thyr said.

Biotin

Though it is a relatively minor player in the vitamin B family, biotin should not be overlooked. It can help resolve a diverse range of symptoms including brittle nails, seborrheic dermatitis, peripheral neuropathy (in diabetics), hair loss, and in some cases, rapid weight loss. Biotin depletion is common during pregnancy. It is extremely safe, and can be given at doses of 10 mg per day without ill effects.

Vitamin B Injections

Physicians should encourage patients to eat as many vitamin B-rich foods as they can (see “B’s on the Burner,” below). But Dr. Thyr has found that for a lot of patients, a vitamin B injection can be an effective jump-start toward health and well-being. The injections cost between $13 and $15 per shot, so it’s a very inexpensive treatment.

It is in the area of infertility treatment that Dr. Thyr has seen vitamin B shots work some of their strongest magic. “For my patients who are having trouble getting pregnant, I give once-weekly intramuscular injections of B6, folic acid, and B12, one cc each, in a 3 cc syringe.” She gives the shots in the context of other lifestyle modifications and natural therapies including omega-3 fatty acids, identification and elimination of any problem foods (gluten is a common culprit). “I’ve had a few patients become pregnant within 6 months to a year of starting treatment, and along the way, they tend to feel much better.”