Nutritional Advice for Persons with Porphyria
Herbert L. Bonkovsky, MD
Wake Forest Baptist Medical Center in Winston-Salem, North Carolina
Professor of Gastroenterology
Jessy Philip, RD, PhD
Carolinas Health Care System, Charlotte, NC
Department of Medicine, Univ of CT Health Center and Univ of NC School of Medicine
Overview: Good nutrition is important for all of us, including those with Porphyria. For the most part, persons with Porphyria should follow the sensible and usual dietary advice of the Centers for Disease Control, the US Department of Agriculture, and other responsible and reputable governmental agencies.
Because over-nutrition and obesity are such a great problem in the USA and other western countries, it is important that patients with Porphyria do their best to avoid becoming obese or gaining weight beyond their ideal body weight. The acute Porphyrias(Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and ALAD Deficiency Porphyria(ADP))may be made worse by prolonged fasting or severe 'crash'dieting, because, in these forms of Porphyria, glucose and other carbohydrates help to repress the activity of hepatic delta-aminolevulinic acid synthase (ALAS1), the first enzyme of the heme synthetic pathway. In these forms of Porphyria, uncontrolled up-regulation of ALAS1 in the liver is a necessary component of the metabolic abnormalities that may give rise to acute attacks.
General Advice: There is no special or particular diet required or recommended for persons with Porphyria. Rather, the principles of good and sensible nutrition apply. These principles call for a varied and balanced diet, particularly with avoidance of over-nutrition. Consumption of too many calories, in excess of daily needs for calorie and energy consumption, has emerged as one of the greatest public and personal health problems of Americans. The growing problem of obesity is present in much of the world, not just in North America.
This dietary brochure and downloadable documentshowcurrent general dietary recommendations for Americans, as developed by the Department of Health and Human Services and the Centers for Disease Control. Click HEREto read now, and download for future reference.Such advice should be followed by persons with Porphyria, as well as those without. The keys are adherence to a varied and balanced diet with moderate consumption of carbohydrates, protein, and fats. To reduce the risks of cardiovascular diseases, such as atherosclerosis or heart attacks, the fats should include little or no trans-fats and preferably include a substantial proportion as unsaturated fatty acids (such as olive oil, safflower oil, etc.), rather than saturated fatty acids (such as animal fat). The protein may be in the form of animal or vegetable protein. The carbohydrates should preferably not include large amounts of refined sugars or high fructose corn syrup, although oral or intravenous carbohydrate in the form of dextrose may be prescribed for therapy of acute attacks of Porphyria. However, day in and day out, even persons with one of the acute Porphyrias should not be consuming large amounts of dextrose (sugar) or fructose.
Nutritional Advice for Persons with Acute Porphyria. The acute or inducible Porphyrias include Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and Porphyria due to severe deficiency of ALA dehydratase (ALAD or ADP). Most persons that have one of these forms of Porphyria, all of which are due to inherited deficiencies in one of the enzymes of heme biosynthesis, have no symptoms or signs of Porphyria most of the time. They may, however, occasionally develop acute attacks, usually characterized by severe bouts of abdominal pain with increases in blood pressure and pulse rate and with severe constipation. Sometimes, the pain may be in the chest, back or extremities instead of, or in addition to, the abdomen (belly). Such attacks are characterized by a marked up-regulation of an enzyme in the liver called delta-aminolevulinic acid synthase 1 (ALAS1). This up-regulation leads to a marked over production and urinary over-excretion of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), which are the biochemical hallmarks of acute Porphyric attacks.
The treatment of such acute attacks is focused on decreasing the up-regulation of hepatic ALAS1. This is done by the administration of sugar (dextrose)and by the administration of heme, which must be given intravenously. During acute attacks, patients often have nausea and vomiting, as well as disturbances of normal gastrointestinal function, so that it is necessary for the dextrose to be administered intravenously, as well. If the attacks are less severe, however, patients may be able to take in dextrose orally, such as by adding sugar to orange juice, by sucking on hard candies, etc. During such acute attacks, the usual therapeutic recommendations by experienced physicians are for the daily intake of dextrose or other metabolizable carbohydrates to be approximately 300 grams per day.
It is also important for persons with one of the acute Porphyrias to avoid drugs or other factors that are known to be able to trigger acute attacks. Chief among these are estrogen and especially progesterone. Thus, some menstruating women unfortunately experience monthly symptoms during the middle of their menstrual cycles, around the time of ovulation, when their endogenous production of progesterone is at a peak. Such women may benefit from drugs such as gonadotropin-releasing hormone antagonists (euprolide)or low doses of oral contraceptives, which interrupt their normal monthly hormonal cycles. Some benefit from receiving prophylactic infusions of Panhematin® on a monthly basis, typically administered shortly before the time of the month when they ovulate (mid-menstrual cycle).
A number of drugs and chemicals are capable of up-regulating hepatic ALAS1 and are thus best avoided by persons with acute Porphyria. Such drugs include barbiturates, such as phenobarbital, hydantoins such as phenytoin and carbamazepine, sulfonamides such as sulfamethoxazole or sulfisoxazole (and many others). Another factor that is capable of triggering acute Porphyric attacks is excess intake of alcoholic beverages. Thus, persons with acute Porphyria should avoid any binge drinking. Good general advice is that men should drink alcohol either not at all or not more than two drinksper day and women should drink not at all or not more than one drink of alcohol per day.
Any acute stress such as an acute illness or severe emotional or psychological stress or exhaustion may also trigger acute Porphyric attacks. Therefore, patients with acute Porphyria should receive vaccinations to protect them from preventable acute infections, including annual flu shots, Pneumovax (a vaccination that protects against development of pneumonias), vaccinations to protect against diphtheria, pertussis and tetanus, with booster shots for tetanus at least every ten years, vaccinations to protect against hepatitis A or hepatitis B infection, and for those who have had chicken pox, the vaccination to protect against development of shingles (Zostrix).
There is no convincing clinical or scientific evidence that any particular foods (with the exception of alcoholic beverages, as described above) are capable of triggering or worsening acute Porphyric attacks. There are, however, some foods that have been shown to contain chemical substances that, in large amounts, can up-regulate hepatic ALA synthase 1 (ALAS1). Such foods include charcoal-broiled meats, cabbage, and Brussels sprouts. The amounts of such foods that would need to be eaten in order to produce induction of hepatic ALA synthase 1 have not been carefully studied, but are probably far above the amounts that would be eaten as part of reasonable, well balanced diets. None of these foods needs to be avoided completely by persons with acute Porphyria, unless they have true allergies to them, which are very uncommon. Moderation in all things is the best course of action. The Appendix lists suggested meal plans for persons with acute Porphyria who are of normal weight and with normal daily needs for energy (~30-35 Kcal/kg BW/d).
Dieting in Acute Porphyria. It is important that persons with acute Porphyria avoid crash diets with extreme decreases in daily carbohydrate and caloric intakes. However, it is also important that they avoid obesity. If they already are obese, they should gradually lose weight. This should be done with a formal diet plan and under the supervision of an experienced physician and nutritionist.
Sulfur Containing Amino Acids and Essential Amino Acids. Our normal diets contain proteins. In fact, regular and adequate intake of protein is essential to normal growth and health. Proteins are found in both vegetable and animal sources of foods. The building blocks of proteins are called amino acids. Some of these amino acids, such as methionine and cysteine, contain sulfur. Such amino acids are not the same thing as "sulfa drugs". They are not contraindicated for patients with acute Porphyria. In fact, methionine is one of the nine essential amino acids: if adequate amounts of these nine amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine)are not consumed regularly, deficiencies will develop that can lead to malnutrition and disease. The reason is that humans are unable to make these amino acids and must take them in regularly, in order to achieve and maintain adequate levels to permit their bodies to make the hundreds of thousands of proteins that are essential for good health.
Porphyria Cutanea Tarda (PCT). The major risk factors for the development of Porphyria Cutanea Tarda are excess alcohol intake, cigarette smoking, increased iron, certain chronic viral infections, especially hepatitis C virus and human immunodeficiency virus, and estrogens. About 20 to 25% of persons with Porphyria Cutanea Tarda (PCT) also have a genetic predisposition in the form of a inherited partial deficiency of an enzyme called uroporphyrinogen decarboxylase. However, such a deficiency in itself is not sufficient to produce symptomatic PCT; other factors are also needed.
The main dietary advice for persons with Porphyria Cutanea Tarda is to avoid all alcohol in any form. In addition, adherence to a low iron diet with avoidance of any medicinal iron and with ingestion of limited amounts of liver or red meat, is recommended, at least until remission of active PCT has been achieved. Remission is achieved by the removal of iron, usually by therapeutic phlebotomy, which is the removal of one unit of blood every week or two. This is continued until an iron reduced state has been achieved. Patients with active PCT typically require the removal of eight to twelve pints of blood, although this number is variable. The progress of iron removal is best followed with serial measurements of serum ferritin. The ideal serum ferritin is 50 to 100 ng per ml. Typically, removal of one pint of blood will lead to a decrease in serum ferritin of about 30 ng per ml. An alternative for the treatment of PCT, especially without acquired or inherited iron overload (hemochromatosis)is the use of low dose-antimalarial drugs, such as chloroquine or hydroxy-chloroquine.
Erythropoietic Protoporphyria (EPP). In EPP there is excess production of protoporphyrin by developing red blood cells in the bone marrow. This is due usually to an inherited deficiency in an enzyme called ferrochelatase or heme synthase, the final enzyme in the heme synthetic pathway. A less common form of EPP is caused by an increase in activity of the erythroid form of ALA synthase (ALAS2), the first enzyme of the heme synthetic pathway.
Many persons with EPP have a mild degree of anemia with measures of iron that suggest iron deficiency. Some such persons appear to benefit from iron administration, although often, despite taking medicinal iron, they continue to have low levels of serum iron, increases in iron binding capacity, and low levels of serum ferritin, suggesting that they are not absorbing the iron in a normal way. For unknown reasons, a few persons with EPP and evidence of iron deficiency have seemed to worsen with iron administration. Therefore, use of medicinal iron supplements in EPP should be undertaken carefully and with careful monitoring by an experienced physician.
There also have been a few reports that intake of glucose has led to an improvement in EPP. In addition, the use of intravenous heme (which contains iron)has been found to help improve liver damage in persons with EPP.
For the most part, there is no particular special diet recommended for patients with EPP. A varied well balanced diet with avoidance of excess calories and with assurance of adequate intakes of iron and other minerals and vitamins is recommended.
Rare Cutaneous Forms of Porphyria. Congenital Erythropoietic Porphyria (CEP). CEP is a rare genetic disorder characterized by deficient activity of an enzyme called uroporphyrinogen 3 synthase (also sometimes called uroporphyrinogen co-synthase). It is characterized by severe over-production of uroporphyrin 1, which is manifest at birth and in the neonatal period. There is no particular diet that is indicated or recommended for persons with CEP. The same thing may be said of the rare form of cutaneous Porphyria called Hepatoerythropoietic Porphyria (HEP), which presents in the new born period, as does CEP, but which is due to severe deficiency of uroporphyrinogen decarboxylase (homozygous or compound heterozygous deficiency).
Advice about Vitamins and Minerals: For most Americans who are consuming mixed, well-balanced diets, there is no need for routine use of vitamin or mineral supplements. Persons who consume few dairy products (milk, yogurt, cheese, etc)and older persons, especially women, and those with little exposure to sunlight are prone to develop deficiencies of vitamin D and to have inadequate intake of calcium. Thus, they should have their serum levels of 25-hydroxy vitamin D checked and should seek advice of a well-trained physician or nutritionist regarding supplements of vitamin D and calcium. There is potential harm from the excessive intake of vitamin D or calcium, or of excessive intakes of other fat-soluble vitamins (vitamins A and E). Thus, moderation in intake is best. There is little harm, but also little likelihood of benefit, in the intake of water-soluble vitamins (vitamins B and C). Iron may trigger or worsen Porphyria Cutanea Tarda, and it may also increase levels of hepatic ALA synthase 1. Thus, it should not be taken in medicinal form unless there is evidence of iron deficiency. There is little reason for anyone with Porphyria (or most without Porphyria)to take in supplemental copper, zinc, selenium, chromium, silver, gold, or othermetals.
Advice about Herbal Remedies and Dietary Supplements. Herbal remedies and dietary supplements (HDS) have become popular in the USA and in many other parts of the world. In fact, there is widespread irrational enthusiasm for taking such supplements. We recommend against their use because the composition and purity of them are uncertain. They are unregulated by the US Food and Drug Administration, and they have not been shown to be safe and effective. Many of them probably contain chemicals that are capable of up-regulating hepatic ALAS1 and thus of triggering or exacerbating acute Porphyria. In addition, they often are adulterated with potentially toxic substances, such as heavy metals.
Appendix - Recommended Diet Plans for Persons with Acute Porphyria.
Eat easily digestible foods, but predominantly carbohydrates. For example: bread, cereal, porridge, rice pudding, yoghurt, milk shakes made with bananas and milk, Avoid acidic foods and fruits, and try some nuts and seeds, such as pumpkin seeds for their calories, vitamins and minerals.What foods to avoid if you have porphyria? ›
People with porphyria are advised to maintain a diet with an average or higher-than-average intake of carbohydrates, which can lessen disease activity—but they are also advised to avoid refined sugars, corn syrup and heavily processed foods.Are there any special requirements for porphyria? ›
General Advice: There is no special or particular diet required or recommended for persons with Porphyria. Rather, the principles of good and sensible nutrition apply. These principles call for a varied and balanced diet, particularly with avoidance of over-nutrition.Why do carbs help porphyria? ›
When the body metabolizes carbohydrates, carbohydrates are broken down into glucose (sugar). Glucose suppresses an enzyme used in heme production. For people with acute porphyria, this helps reduce the amount of heme precursors in the blood. Glucose infusions or ingesting sugars are sometimes used to treat attacks.Does sugar help porphyria? ›
Glucose can diminish excess excretion of heme precursors, which, in turn, can prevent an attack or can hasten recovery from an attack of the acute porphyrias. Therefore, it is suggested that when patients cannot consume carbohydrates due to nausea or vomiting, glucose should be administered intravenously.What vitamins help porphyria? ›
- oral administration of activated charcoal, which helps to absorb excess porphyrins.
- daily supplementation with beta-carotene (vitamin A) as part of long-term treatment.
- Medication is stopped.
- Urine specimens sent to the laboratory for the determination of ALA, PBG and porphyrins.
- The patient is given symptomatic treatment with paracetamol-codeine compound for pain.
- And is told to ensure an adequate intake of oral fluids and carbohydrates.
Treatment may include: Injections of hemin, a medication that is a form of heme, to limit the body's production of porphyrins. Intravenous sugar (glucose), or sugar taken by mouth, if able, to maintain an adequate intake of carbohydrates.
Pyridoxine deficiency, induced by feeding deoxypyridine in acute intermittent porphyria, decreased urinary excretion of heme precursors delta-aminolevulinic acid and porphobilinogen.What is the most common cause of acquired porphyria? ›
Porphyria cutanea tarda (PCT) typically is acquired rather than inherited, although the enzyme deficiency may be inherited. Certain triggers that impact enzyme production — such as too much iron in the body, liver disease, estrogen medication, smoking or excessive alcohol use — can cause symptoms.
These disorders are usually inherited, meaning they are caused by gene mutations link passed from parents to children. If you have porphyria, cells fail to change chemicals in your body—called porphyrins and porphyrin precursors—into heme, the substance that gives blood its red color.Can porphyria cause weight gain? ›
"Unfortunately, because of the therapeutic high carbohydrate intake, patients with hepatic porphyrias are prone to weight gain.What are the two enzymes that lead interferes causing porphyria? ›
PBG and uroporphyrin may also appear in the urine and in the bone marrow in severe lead intoxication. The accumulations of porphyrins and their pre- cursors are largely due to the inhibition by lead of the two enzymes, ALA- dehydratase and ferrochelatase (SASSA et aI., 1975).Does porphyria affect the brain? ›
Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic and peripheral nervous system. Due to their relative rarity and their chameleon‐like presentation awareness among neurologists is low and delayed diagnosis and misdiagnosis are common.Can porphyria cause high cholesterol? ›
In conclusion, in patients with asymptomatic acute porphyria an increase of total and LDL-cholesterol was found. The cardiovascular risk conferred by this factor may be attenuated by increased HDL-cholesterol and apo-A1.Does porphyria cause neuropathy? ›
Neuropathy occurs in 20-68% of porphyria patients. The typical pattern of porphyric neuropathy is predominantly motor axonal neuropathy. Abdominal pain usually starts days to weeks before neuropathy. The motor neuropathy is normally symmetrical and begins in proximal part of the upper extremities.Does porphyria cause fatigue? ›
Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common. Nervous system symptoms are numerous.Can porphyria affect eyesight? ›
Despite careful follow-up and intensive treatment, scleral and corneal necrosis can be progressive and results in the loss of vision or even the loss of eye. Further studies regarding the care of patients with porphyrias are required to treat these rare ophthalmic conditions more effectively.Does sunscreen help porphyria? ›
The skin/cutaneous porphyrias are characterised by reactions to visible light. Therefore conventional sunscreens formulated to protect against just ultraviolet (particularly UVB) are ineffective. For all skin porphyrias, reflectant sunscreens that are based on titanium dioxide or zinc oxide will be more effective.What are the mental symptoms of porphyria? ›
Acute intermittent porphyria mimics a variety of commonly occurring disorders and thus poses a diagnostic quagmire. Psychiatric manifestations include hysteria, anxiety, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness ranging from somnolence to coma.
Acute intermittent porphyria is the most common form of acute porphyria in most countries. It may occur more frequently in northern European countries, such as Sweden, and in the United Kingdom. Another form of the disorder, hereditary coproporphyria, has been reported mostly in Europe and North America.What blood pressure medications treat porphyria? ›
Beta blockers: All beta blockers are safe in porphyria and their use is recommended. ACE inhibitors: Captopril, enalapril, lisinopril and quinapril are safe. It is likely that the rest of the class are safe as well. We have used both enalapril and ramipril freely in our patients without problem.What is the new medication for porphyria? ›
Intravenous hematin is the treatment of choice, both for treatment of severe acute attacks and for prevention of recurrent attacks. Givosiran, which is given monthly by subcutaneous injection, is a newer treatment option.
Gross examination of the urine can provide a valuable clue, since urine of porphyria cutanea tarda patients is red to brown in natural light and pink to red in fluorescent light.What is the life expectancy of someone with porphyria? ›
For most patients, the life expectancy is similar to that of persons without porphyria.Is porphyria an autoimmune disease? ›
The aetiology of porphyria cutanea tarda (PCT) has not been elucidated, but the possibility of an autoimmune mechanism has been proposed. We report a case of an unknown clinical combination of PCT with autoimmune hypothyroidism, alopecia universalis and vitiligo with thyroid and parietal cell circulating antibodies.What color is associated with porphyria? ›
The terms porphyrin and porphyria are derived from the Greek word porphyrus, meaning purple. Urine from some Porphyria patients may be reddish-purple in color due to the presence of excess porphyrins and related substances in the urine, and the urine may darken after exposure to light.Can porphyria be caused by stress? ›
In addition to being harmful to physical and mental health, stress is also a potential trigger for porphyria attacks.What famous person has porphyria? ›
Famous cases have been linked to porphyria, such as Prince William of Gloucester, a paternal cousin of the present British Queen Elizabeth II. As such he also descended from King George III. Historians long hypothesized that his madness may have been due to an undiagnosed family history of porphyria.Can you have mild porphyria? ›
The symptoms of porphyria vary depending on type. Symptoms range from mild to severe. Some people with porphyria have no symptoms. In some cases, symptoms can be life-threatening unless treated.
The types that affect the nervous system are also known as acute porphyria, as symptoms are rapid in onset and short in duration. Symptoms of an attack include abdominal pain, chest pain, vomiting, confusion, constipation, fever, high blood pressure, and high heart rate. The attacks usually last for days to weeks.How does porphyria cause pain? ›
Porphyrias are caused by decreased enzyme activity in the heme biosynthetic pathway leading to overproduction of heme precursors if demand increases. This can cause symptoms such as abdominal pain, nausea and vomiting, constipation, tachycardia and hypertension.Does porphyria affect the heart? ›
Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF).Can you donate blood if you have porphyria? ›
Must not donate if:
If the potential donor suffers from Acute Porphyria, Acute Intermittent Porphyria (AIP), Varigate Porphyria (VP) or Hereditary Coproporphyria (HCP), it is 12 months or more since their last acute attack and they have no current skin lesions, accept.
Periodically drawing blood (phlebotomy) to reduce the iron in your body, which decreases porphyrins. Taking a drug used to treat malaria — hydroxychloroquine (Plaquenil) or, less often, chloroquine (Aralen) — to absorb excess porphyrins and help your body get rid of them more quickly than usual.What part of the body does porphyria affect? ›
Porphyrias are rare disorders that mainly affect the skin or nervous system. These disorders are usually inherited, meaning they are caused by gene mutations link passed from parents to children.What does porphyria pain feel like? ›
The most commonly reported debilitating symptoms are diffuse severe pain affecting the abdomen, back, or limbs; other common attack signs and symptoms include nausea and vomiting, constipation, hypertension, motor weakness, insomnia, or anxiety [1–3, 5].Does porphyria cause back pain? ›
Acute intermittent porphyria, which causes abdominal pain and neurologic symptoms, is the most common acute porphyria. Many people never experience symptoms. Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental health symptoms.