GI Nutrition: GI Nutrition: Vitamins and Essential Fats

0:00Welcome to Board Pearls. This is episode three of four of the GI Nutrition chapter, in the Special Populations and Acute or Supportive Care module. This episode is the vitamins and essential fatty acids, each traced from its job in the body to the picture its deficiency or excess makes. The first patient is a woman with cholestasis who takes cholestyramine, and her case shows why bile acid failure causes all four fat-soluble deficiencies, how vitamin D is repleted, why fasting and antibiotics push up the clotting time, and why medium-chain triglyceride oil can't prevent essential fatty acid deficiency. A man with unexplained cirrhosis shows what too much vitamin A does to the liver. The second patient is a woman on a long-term acid suppressant, and her case shows where B12 absorption fails, how a borderline level is confirmed, and why B12 is checked before folate is given. A man with a carcinoid tumor shows the rash of pellagra. And short cases show the clues to pyridoxine, thiamine, vitamin C, and biotin.

1:03Here's the first patient. A fifty-eight-year-old woman has primary biliary cholangitis with advanced cholestasis and takes cholestyramine for itching. Over months she's lost her night vision and stopped driving at night. A dual-energy x-ray absorptiometry scan shows osteoporosis, and her 25-hydroxyvitamin D is fourteen nanograms per milliliter.

1:24She has fat-soluble vitamin deficiency, with vitamin A deficiency causing her night blindness and vitamin D deficiency contributing to her bone loss. Vitamins A, D, E, and K all need bile salts and intact ileal bile acid recirculation to be absorbed, so anything that disrupts the enterohepatic bile acid cycle causes deficiency. The causes are cholestyramine, ileal disease or resection, severe cholestasis from primary biliary cholangitis, PBC, or primary sclerosing cholangitis, PSC, alpha-one antitrypsin liver disease, cystic fibrosis, and prolonged parenteral nutrition without supplements. She has two of them at once: her cholestasis sends fewer bile salts to her gut, and her cholestyramine binds the ones that arrive. Because one shared mechanism affects all four vitamins, finding one deficiency in her means looking for the other three.

2:21Her night blindness comes first, because it's the symptom that brought her in. Vitamin A deficiency causes night blindness because the eye needs retinal to make rhodopsin. It also causes Bitot spots, patches of keratinized epithelium on the conjunctiva, along with xerophthalmia, hyperkeratosis, and more infections. Deficiency is uncommon in industrialized populations but appears in chronic cholestasis, where there are too few bile salts to dissolve the vitamin, in short bowel syndrome, and on prolonged unsupplemented parenteral nutrition. Night blindness in a patient with cholestasis on cholestyramine points to a bile salt problem rather than an eye problem. Her retinol level is checked, and her vitamin A is replaced.

3:04Her osteoporosis is the second deficiency the shared mechanism predicts, and it needs a defined treatment. Vitamin D deficiency drives metabolic bone disease in PBC and PSC, in inflammatory bowel disease, where inflammation impairs absorption and steroids speed bone loss, in short bowel syndrome, and after bariatric surgery. Repletion starts when 25-hydroxyvitamin D is below thirty nanograms per milliliter, and some authorities use a stricter cutoff of twenty. The options are ergocalciferol, vitamin D two, fifty thousand units weekly for eight to twelve weeks, or cholecalciferol, vitamin D three, one thousand to five thousand units daily, which may raise the level modestly more. Either way the level is re-measured. Calcium is paired with vitamin D, because adequate calcium is needed for vitamin D's effect on bone. Her level of fourteen is below both cutoffs, so she starts weekly ergocalciferol with calcium and a recheck after the course.

4:03Vitamin E fails by the same mechanism, so she's watched for its signs even without them today. Vitamin E, alpha-tocopherol, is an antioxidant in cell membranes that stops lipid peroxidation chains. Deficiency is rare in industrialized populations but causes a sensorimotor neuropathy, cerebellar ataxia, and hemolytic anemia, because red cell membranes are peroxidized faster without it. It appears in abetalipoproteinemia, chronic cholestasis, and extreme fat malabsorption. If she developed unsteadiness and numb feet in the years ahead, vitamin E would be on her list. The vitamin is also used as a drug: eight hundred units daily in patients without diabetes who have biopsy-proven metabolic dysfunction-associated steatohepatitis, limited by cautions about prostate cancer and hemorrhagic stroke.

4:56Vitamin K is the deficiency that can turn dangerous within days, and her case shows when. Vitamin K is the cofactor for hepatic gamma-carboxylation of clotting factors two, seven, nine, and ten and of proteins C and S. It comes from two sources, leafy greens in the diet and synthesis by colonic bacteria. Fasting alone causes only modest depletion, because the bacteria keep making it. Fasting plus broad-spectrum antibiotics removes both sources at once, and in a patient on warfarin a stable international normalized ratio, INR, can rise to dangerous levels within days of starting the antibiotics. If she were admitted, not eating, and started on antibiotics while taking warfarin, her INR would be watched for that rise. Vitamin K is replaced under the skin or by mouth. Intravenous vitamin K carries a risk of anaphylaxis and is given slowly, with the INR guiding the dose.

5:54Vitamin A also causes harm in excess, and the liver is where it shows. A forty-four-year-old man has ascites and varices, with no alcohol use, negative viral and autoimmune tests, and no metabolic risk factors, and his team is about to call it cryptogenic cirrhosis. Asked again, he mentions years of high-dose vitamin A from an alternative practitioner for his skin. He has vitamin A hepatotoxicity. Vitamin A is stored in hepatic stellate cells, and chronic intake above ten times the recommended allowance, fifty thousand units a day or more, causes stellate cell hypertrophy, perisinusoidal fibrosis, and portal hypertension that can look like cirrhosis without alcohol or viral hepatitis. The mechanism is direct: the stellate cells that store vitamin A are the same cells that, once activated into myofibroblasts, lay down the matrix of fibrosis. Patients often don't volunteer the history, which usually comes from acne treatment or alternative medicine, so supplements are asked about by name. His vitamin A is stopped. A single very large dose causes something different, pseudotumor cerebri, with headache, papilledema, and visual change, rather than fibrosis.

7:11Fat malabsorption that empties fat-soluble vitamins can also empty the essential fatty acids. Deficiency develops on long-term parenteral nutrition without lipid, in severe fat malabsorption, and with some very low-fat chronic diets. Humans can't make linoleic acid, an omega-six, or alpha-linolenic acid, an omega-three, because human enzymes can't place a double bond beyond the ninth carbon. Without them, the body turns oleic acid into mead acid, an abnormal fatty acid that doesn't normally accumulate. The diagnostic signature is a triene-to-tetraene ratio, mead acid divided by arachidonic acid, above zero point two. The clinical picture is scaly dermatitis with bronzed skin, hair loss, poor wound healing, hepatic steatosis, and growth failure in children. Treatment is intravenous lipid: once or twice weekly to prevent deficiency on long-term parenteral nutrition, and daily for established deficiency. That's why the woman on home parenteral nutrition in episode two gets lipid twice weekly.

8:15If the first woman's fat malabsorption were managed with medium-chain triglyceride, MCT, oil, it still wouldn't protect her from essential fatty acid deficiency. MCT fatty acids, caprylic and capric acid, are eight to twelve carbons long and lack the eighteen-carbon chain of linoleic and alpha-linolenic acid, and the body can't lengthen or desaturate them into either one. MCT oil is a useful calorie source in fat malabsorption, because it's absorbed directly into portal blood without micelles or chylomicrons, and it's standard in chronic pancreatitis and short bowel syndrome. A man with short bowel syndrome whose only fat is MCT oil, with no parenteral lipid, who develops a scaly rash and a ratio of zero point three, needs long-chain lipid.

9:01Now the second patient, whose deficiency is a water-soluble vitamin. A seventy-three-year-old woman has taken a proton pump inhibitor daily for many years. Over months her feet have gone numb and she's unsteady walking in the dark. She has a macrocytic anemia and a serum B12 of two hundred eighty picograms per milliliter, and her primary care doctor started folic acid last week.

9:25She most likely has B12 deficiency, causing her neuropathy and macrocytic anemia. Water-soluble vitamins aren't stored in large amounts, so most deficiencies appear within weeks to months. B12 is the exception, because hepatic stores last two to five years, which is why her deficiency took years to appear after her proton pump inhibitor, PPI, began.

9:47Her drug points to where her absorption failed, which matters because each failure point has its own cause and its own treatment. B12 absorption takes four steps. Gastric acid releases B12 from dietary protein. Haptocorrin, also called R-protein, binds it in the stomach and protects it through the duodenum. Pancreatic enzymes break down R-protein and hand B12 to intrinsic factor from the gastric parietal cells. The intrinsic factor complex is absorbed by cubilin receptors in the terminal ileum. PPI-induced hypochlorhydria blocks the first step, causing food-cobalamin malabsorption in five to fifteen percent of older adults. Pernicious anemia destroys parietal cells and so removes intrinsic factor, and it's marked by anti-intrinsic factor and anti-parietal cell antibodies with atrophic body gastritis on biopsy. Chronic pancreatic insufficiency disrupts the R-protein step. Ileal disease or resection removes the cubilin receptors, and that malabsorption doesn't respond to oral B12, which is why the man with short bowel syndrome in episode two needs B12 for life. Her PPI explains the first step, but her intrinsic factor antibodies are still checked for a second cause.

11:01Her level is borderline, so it needs confirming before it's called deficiency. Serum B12 is the screening test, and two hundred to four hundred picograms per milliliter is borderline, confirmed with methylmalonic acid, MMA, and homocysteine. MMA is the more specific tissue marker, because it accumulates only when the B12-dependent enzyme methylmalonyl-CoA mutase fails, while folate deficiency raises homocysteine but not MMA. Both are high in her, so she has B12 deficiency, not folate deficiency alone.

11:31The folate she was started on is the most dangerous part of her case. High-dose folate corrects the megaloblastic anemia of B12 deficiency but not the neurologic damage, so subacute combined degeneration of the cord keeps progressing, because folate can't replace B12 in the methionine synthase reaction that maintains spinal cord myelin. That's why B12 is always checked before folate is started: once folate is given, the blood count improves and the patient looks better while the cord degenerates silently. Her numb feet and unsteadiness in the dark mean her cord is already injured. Her B12 is replaced with intramuscular cyanocobalamin, one thousand micrograms weekly for one to two months and then monthly, and her folate is continued only alongside it.

12:16Had her anemia been folate deficiency instead, the blood picture would have looked the same without the neurologic damage. Folate deficiency causes a megaloblastic anemia hematologically identical to B12 deficiency, but without the cord syndrome, because folate isn't needed for the methionine synthase reaction that maintains myelin. The settings are alcohol use disorder, which impairs absorption and increases urinary loss; pregnancy, where fetal demand raises requirements; the folate antagonists methotrexate and trimethoprim; celiac disease with proximal villous atrophy, covered in chapter ten; and chronic hemolysis, which uses up folate. Repletion is folic acid, one to five milligrams by mouth daily.

12:59Her pre-treatment folate level also mattered for another reason. Small intestinal bacterial overgrowth, SIBO, produces a dissociation: the bacteria consume B12 in the gut lumen, lowering serum B12, and make folate, raising serum folate. So a low B12 with a high folate is essentially diagnostic of SIBO among malabsorption syndromes, while in other malabsorption states both are low. Had her folate been high before treatment alongside a low B12, overgrowth would be looked for and treated along with her B12.

13:32A rash can be the first clue to a vitamin deficiency, and pellagra is the classic example. A sixty-two-year-old man has a small bowel neuroendocrine tumor with liver metastases and carcinoid syndrome. He now has a dark, scaly band around his sun-exposed neck and upper chest, with diarrhea and forgetfulness. He has pellagra, from niacin deficiency, with the four Ds of dermatitis, diarrhea, dementia, and death, and the band is the Casal necklace. The rash is photosensitive because niacin is needed to repair DNA damaged by ultraviolet light. The settings are corn-based diets without nixtamalization, because corn niacin stays bound until the corn is treated with alkali, which is why traditional Mexican cooking soaks corn in lime water; chronic alcohol use disorder; and carcinoid syndrome, where the serotonin-secreting tumor consumes the tryptophan the body would use to make niacin. His tumor is the cause, and he's treated with oral nicotinamide, two hundred fifty to five hundred milligrams daily, instead of having his rash called a drug reaction.

14:36Niacin's link to tryptophan leads to pyridoxine, which is needed to convert tryptophan to niacin and which drugs commonly deplete. Pyridoxine is a cofactor for many transamination and decarboxylation reactions, including heme synthesis and neurotransmitter metabolism. Isoniazid binds and inactivates it, causing peripheral neuropathy, so a man starting long-term isoniazid takes prophylactic pyridoxine, twenty-five to fifty milligrams daily, as standard care. Hydralazine and penicillamine deplete it the same way. Too much pyridoxine also causes a sensory neuropathy, above five hundred milligrams daily for prolonged periods, so a woman with numb feet who takes high-dose pyridoxine supplements is asked her dose.

15:21Thiamine deficiency is the water-soluble deficiency that's treated before it's confirmed, because the brain is at stake. Thiamine is the cofactor for transketolase and pyruvate dehydrogenase. Deficiency causes wet beriberi, high-output heart failure from impaired heart muscle energy metabolism; dry beriberi, a sensorimotor neuropathy; and Wernicke encephalopathy, with confusion, ophthalmoplegia or nystagmus, and ataxia from energy failure in the thalamus and mammillary bodies. Wernicke encephalopathy is a clinical diagnosis, treated empirically with thiamine five hundred milligrams intravenously three times daily for two to three days, then two hundred fifty milligrams daily for five to seven days. Thiamine is given before any glucose for the reason covered in episode one: glucose without thiamine drives glycolysis, but pyruvate can't enter the citric acid cycle, energy fails in vulnerable thalamic neurons, and Wernicke is triggered. Untreated or undertreated, it progresses to Korsakoff syndrome, with permanent anterograde amnesia and confabulation. That was the confused, unsteady man with alcohol use disorder in episode one, and his alcohol use is also a reason to check his folate.

16:35Vitamin C deficiency shows up in the skin and gums, because the vitamin is needed to build collagen. Scurvy causes perifollicular hemorrhage, corkscrew hairs, bleeding gums, poor wound healing, and impaired iron absorption, because vitamin C is a cofactor for the prolyl and lysyl hydroxylases that crosslink collagen, and without it fragile capillaries bleed. Oral vitamin C, five hundred to one thousand milligrams daily, reverses it within days to weeks.

17:05Biotin matters less as a deficiency than as a cause of misleading lab results. Deficiency is rare. It occurs with chronic raw egg white consumption, because avidin in raw egg white binds biotin and blocks its absorption, which cooking prevents by denaturing the avidin, and with certain anticonvulsants. It causes alopecia, scaly dermatitis, and conjunctivitis. Supplement-level doses of biotin interfere with thyroid and troponin assays, so a surprising thyroid or troponin result prompts a question about biotin. Pantothenic acid deficiency is essentially never seen on its own outside experimental settings.

17:45Here are the traps the boards set in the fat-soluble vitamins. Cholestyramine and cholestasis both cause fat-soluble vitamin deficiency, and they can act in the same patient. Night blindness with cholestasis is vitamin A deficiency from too few bile salts. Vitamin D is repleted below a level of twenty to thirty, and always with calcium. One fat-soluble deficiency means checking for the other three. Unexplained cirrhosis needs a supplement history, because chronic vitamin A excess causes fibrosis, while a single large dose causes pseudotumor cerebri. Fasting plus antibiotics can send the INR up sharply in a patient on warfarin. Intravenous vitamin K is given slowly because of anaphylaxis. And MCT oil can't treat or prevent essential fatty acid deficiency.

18:31For the water-soluble vitamins, the traps are these. Long-term PPI use causes B12 deficiency in older adults. Oral B12 doesn't work after ileal resection. A borderline B12 is confirmed with MMA. Folate is never started before B12 is checked, and a recovering blood count doesn't mean the cord is safe. A low B12 with a high folate points to bacterial overgrowth. The Casal necklace is pellagra, not a drug rash. Isoniazid needs pyridoxine, and too much pyridoxine also causes neuropathy. Thiamine goes before glucose and at full dose for Wernicke. And biotin can explain a strange thyroid or troponin result.

19:11So, start to finish. Expect fat-soluble vitamin deficiency whenever bile acids or fat absorption fail, and look for all four. Vitamin A deficiency causes night blindness, and chronic excess of fifty thousand units a day or more causes stellate cell fibrosis that can pass for cryptogenic cirrhosis. Replete vitamin D below twenty to thirty with weekly ergocalciferol or daily cholecalciferol, plus calcium. Vitamin E deficiency causes neuropathy, ataxia, and hemolysis. Fasting plus antibiotics depletes vitamin K fast. Essential fatty acid deficiency, with a ratio over zero point two, needs long-chain lipid, not MCT oil.

19:52Trace B12 deficiency to the step that failed, confirm a borderline level with MMA, and never give folate without checking B12. Folate deficiency follows alcohol, pregnancy, folate antagonists, celiac disease, and hemolysis, and a low B12 with a high folate means bacterial overgrowth. Pellagra comes with alcohol, carcinoid syndrome, or untreated corn and is treated with nicotinamide. Give pyridoxine with isoniazid, and give thiamine before glucose, at five hundred milligrams three times daily for Wernicke. Scurvy causes perifollicular and gum bleeding, and biotin distorts thyroid and troponin assays.

20:34Episode four, the last of the chapter, is the minerals and trace elements.

20:39For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode three of four of chapter thirty-two, and I'll see you in the next one.