Herbal Medicines and Nutrients for Sickle Cell Anemia
Multiple studies have now shown that a blend of herbs can effectively treat sickle cell anemia. One herbal formula was clinically proven effective but failed to succeed because of a combination of corruption and manufacturing mishaps. Other herbs and nutrients have also proved to improve symptoms.
What is sickle cell disease?
Sickle cell disease – which can develop into anemia – is thought to be primarily a genetic (and possibly epigenetic) disease produced by abnormal hemoglobin production, which changes the shape of red blood cells into a crescent or sickle shape. These will transport less oxygen to the cells, and can reduce blood flow. It has been prominent among those of African or Middle Eastern descent, as well as South and Central America.
Over 12 million people around the world have sickle cell anemia. According to the Sickle Cell Disease Association of America, between 45,000 and 90,000 infants are born with sickle cell each year in the U.S. Around the world, some 300,000 children are born with serious sickle cell disease.
Over half of infants who are born with the disorder die within the first five years of life.
Because the sickling of red blood cells can halt blood flow to different parts of the body, a variety of symptoms can occur. Symptoms of sickle cell anemia include periods of intense pain, rapid heart rates, yellowing of skin – jaundice, vision issues, skin ulcers, confusion, infections of the urinary tract, lungs bones and/or gallbladder and others. Episodes of intense pain can be excruciating.
Sickle cell anemia is difficult to treat. Conventional medicine typically aims to manage and control symptoms, often with the drug hydroxycarbamide along with pain-killers. Hydroxycarbamide inhibits DNA replication, which can slow the production of sickle cells.
Hydroxycarbamide treatment also comes with a number of potential adverse and toxic side effects, including bone marrow toxicity, liver toxicity, nausea, vomiting, diarrhea, constipation, mucositis, hair loss, problems with blood urea and creatinine among others.
Niprisan herbal extract formula
In the 1990s, scientists from Nigeria’s National Institute for Pharmaceutical Research and Development (NIPRD) developed an herbal formulation made with extracts from several herbs. The herbal combination extract was initially called Nicosan – but later became known as Niprisan (as well as Hemoxin and NIX-0699).
The Niprisan herbal extract formulation has shown significant success in clinical research.
Research on sickle cell with Niprisan included phase I, II and IIb trials.
Nicosan was developed based upon traditional herbal formulation. The name was changed to Niprisan, and it was patented and offered to the public in 2006. Due to a combination of corruption and lack of production capacity,11 the launch failed. The patent on Niprisan expired in 2017, and there are some indications it may be re-introduced to the market.
While Niprisan is not a cure for sickle cell anemia, it does significantly reduce episodes according to studies.
A 2001 Phase IIb clinical trial1 studied 82 patients with sickle cell anemia. They were aged from 2 years to 42 years old. The patients were given either the Niprisan herbal formula or a placebo. The patients kept dairies and were visited by doctors in their homes on a weekly basis, and visited the clinic monthly for assessments.
Among the patients given the Niprisan, 73% had no sickle cell crisis during the twelve-month trial. The rest of the Niprisan group (27 percent) had fewer and less severe sickle cell crises.
Another 2001 clinical trial2 tested 69 patients. They were divided into two groups, of 33 and 36 patients. The trial was a cross-over trial, and lasted 12 months. (Cross-over means that for half the period, one group got the extract while the other group got the placebo.
This study found that Niprisan significantly reduced painful episodes. It also reduced bone pain and the number of hospital visits among the Niprisan groups.
The researchers reported:
“Niprisan was efficacious in the prophylactic management of patients with sickle cell disease …”
Niprisan has been shown to have no significant adverse side effects in its clinical trials. In the first clinical trial noted above, the researchers reported:
“Acute toxicity to the liver assessed by the activities of liver enzymes, indicate that NIPRISAN® is safe. Renal function assessed by the serum levels of creatinine and blood urea nitrogen remained normal.”
What are the herbs in Niprisan?
Based on a traditional African healing remedy for treating sickle cell-like symptoms, the primary constituents of Niprisan or Nicosan are derived from extracts of the following plants:
• Piper guineense seed: the West African pepper or Guinea pepper – a relative of the Ayurvedic long pepper – used to make black pepper.
• Pterocarpus osum stem: an African timber with many relatives.
The central active constituents of these Niprisan herbs include piperine, chavicine, capsaicin and cubebin.
It should be noted that it is not advisable to combine Niprisan or Nicosan with pharmaceutical medications for sickle cell anemia. This is especially for drugs that are considered CYP3A4 type drugs, as Niprisan was found the inhibit CYP3A4 drugs in a 2015 study.3
Other plant medicines for sickle cell disease
Traditional healers have utilized other and similar herbs to combine into similar formulations to treat sickle, with clinical success. These include Piper cubeba and Aframomum melegueta. These two pungent pepper-like compounds have the ability to reduce pain, due to their capsicum and piperine content.
Fagara (Zanthoxylum macrophylla)
Another promising traditional anti-sickle cell herb gaining attention is Fagara (Zanthoxylum macrophylla, previously Fagara zanthoxyloides and Fagara macrophylla). Fagara is a prickly-ash relative. The root bark from this plant has been shown to dramatically reduce sickle cell formation.
Fagara constituents thought to inhibit sickle include burinabans A, B and C. Fargara has also gained notoriety as an anti-malaria medicine.
In a 2005 study from Nigeria’s Abia State University,4 researchers tested blood samples of sickle cell patients. They added a water extract of Fagara to the blood samples at different dilutions. After a one-hour incubation period, the researchers found the number of sickle cells in the blood samples were reduced from an average of 80 percent to an average of 38 percent. That means the sickles in the blood were cut by more than a half within an hour.
Following is a clinical description written in the Journal Anemia:5
“Doctors in Nigeria use fagara (F. zanthoxyloides) to reduce the painful crisis of the genetic disease, sickle cell anemia. This herb has a variety of unusual properties that reduce platelet and blood cell sticking. After reading the reports from Nigeria many years ago, I decided to try fagara’s relative prickly ash bark for the same indication. I made a simple tincture of 50% prickly ash bark and 50% ginkgo leaf, and gave it to a young African-American girl in the first grade who constantly missed school and needed to be hospitalized 3-4 times per year due to the painful sickle cell crisis. I gave her about 25 drops three times a day. She immediately stopped having serious problems, her thinking was no longer fuzzy, the frequency of her attacks went down to about one per year, and the severity of the attacks decreased appreciably. This success has continued through the years, as long as she takes her medicine. I saw her last year, and she has blossomed into a beautiful junior high school student, the sickle cell disease now only a bit-player in the background of her life. Another of my patients had lived with the disease his entire life, with almost constant pain, and bimonthly crisis. I gave him 35 drops three times per day, and he immediately improved in the same way as the young girl. This improvement in both frequency of attacks and level of pain has persisted in three of my long-term patients over many years. The wholesale cost of this medicine is less than $20 per month at full dosage. My biggest fear is that this knowledge will be co-opted by a pharmaceutical company, and made available to the many suffering children only at an exorbitant cost.”
Pigeon pea (Cajanus cajan)
Pigeon pea is a legume that is part of the diet in Southern Asia, Africa and India. It is a significant source of protein and is made into flour, used in soups and curries. It is a major component of dal soup as well. Pigeon pea is a complete source of protein, containing all the necessary and some unnecessary amino acids.
Cajanus cajan is mentioned above in the case research, but this has also undergone clinical study. University of Lagos researchers conducted a single-blind placebo-controlled clinical trial6 in 2005 with 100 sickle cell patients. The group given the Cajanus cajan had fewer painful episodes during the treatment period. Pain episodes decreased from 207 to 191, while the placebo group had increased pain episodes (from 109 to 164) during the treatment period.
Furthermore, liver enlargement decreased from 55% to 33% in the Cajanus group, while the placebo group’s liver enlargements increased during the treatment period.
One particular extract of Cajanus is called Ciklavit. This has been the subject of other research, also showing its ability to inhibit sickling activity in the blood.
Tropical Almond tree (Terminalia catappa)
Terminalia catappa grows throughout Africa, Asia and Australia. It can grow to 90 feet tall. Extracts from the leaves of the tree have been used as a medicinal therapeutic in native African medicine.
In a 2003 study, researchers tested7 extracts from different aged leaves from the tree. They tested extracts from the green leaves, the red-brown leaves, and freshly fallen red-brown leaves. The researchers tested the extracts on blood samples from sickle cell anemia patients.
The research found that extracts from the freshly fallen red-brown leaves had the most antisickling effect. Water extracts and alcohol extracts produced a reduction of 77 percent in 90 minutes, and 78 percent after 180 minutes of incubation.
Cissus populnea L.
Cissus is in the grape family, and its fruits are similar to grapes. A 2003 study from Nigeria’s University of Ibadan8 tested water extracts and alcohol extracts of Cissus for its antisickling activity.
The research found that Cissus had a 62 percent and 53 percent reduction in sickling activity in blood samples of sickle cell patients.
Cissus is the central component of the antisickling herbal formula called Ajawaron. The same study reported that Ajawaron also inhibited sickling in patients’ blood samples.
Other promising sickle cell treatments include fermented green fruit or leaf of Carica papaya.
In a 2005 study.12 researchers tested blood cells taken from sickle cell patients in the laboratory. The green papaya was fermented for five days. The fermented green papaya resulted in 87% inhibition and 74 percent reversal of sickling in the blood samples taken from sickle cell patients.
Pepper elder (Peperomia pellucida)
Pepper elder has been used as a medicinal herb in South America and Africa for centuries. In a 2015 study of Peperomia pellucida extrac, researchers found it inhibited sickling among blood samples of sickle cell patients. The researchers found it inhibited sickling by 57 percent.
The researchers concluded:
“These results showed that P. pellucida has a role in the treatment of sickle cell disorders and a candidate for further investigations.”
Coconut water (Cocos Nucifera)
A treatment that has been conferred anecdotally for sickle cell for generations is coconut water. There is, however, some research confirming the potential of coconut water to aid the sufferer.
In a 2016 study published in the Journal of African Association of Physiological Sciences,20 researchers tested 30 blood samples from sickle cell anemia patients. The researchers incubated the blood with coconut water and found that this helped protect red blood cells from osmotic destruction. The destruction of blood cells through osmotic pressure is one of the highlights of sickle cell disease.
Other studies have shown that coconut water supports blood health and may assist with reducing pain episodes due to its nutrient content. This is the conclusion of a 2018 review of research from Nigeria’s University of Calabar. The combination of minerals and phytonutrients appears to support blood health and the creation of healthy red blood cells.
Other traditional herbs
Indigenous traditional healers have been using a variety of other plant medicines to manage sickle cell anemia. Most of the above plant medicines originated in this population.
Some of these plants, according to some healers, have had clinical success. In a 2016 study from Nigeria’s University of Benin,21 researchers surveyed traditional herbal treatments from 125 locations in Southern Nigeria.
The researchers interviewed 500 people, 79 percent of whom were traditional healers and 27 percent were herb traders. The interviews found that an astounding 170 different plant medicines were used in treatments for sickle cell.
The research found that most of these plants were harvested in the wild.
Of the various plants, the ones having the greatest treatment value comparatively were key lime (Citrus aurantifolia) and Newbouldia laevis – an African bush.
Nutritional strategies for sickle cell
A 2017 study from Nigeria followed 415 sickle cell patients.18 The research measured the effect of different strategies in reducing sickle cell crises. Besides the use of medications, the research found that drinking plenty of water and “soothing herbs” were the most associated with reduced pain crisis frequency.
Beyond this, there are a number of nutrients that can have an antisickling effect according to the research. For example, the amino acid Phenylalanine has been shown to be a significant antisickling agent. This may be one of the reasons that pigeon pea is a successful therapy, as 100 grams of pigeon pea contains 1858 milligrams of phenylalanine.
Other amino acids are also important in helping control the disease. Amino acids have the effect of modulating the red blood cell membranes. This, in turn, affects the hemoglobin concentration, decreasing the tendency for sickling.
Antioxidants are also important nutritional compounds to help control sickle cell anemia. Antioxidants like vitamin C and vitamin E have been shown to be depressed in sickle cell patients.9
Vitamin B12 may also be important in sickle cell anemia. A 1995 study of 85 sickle cell patients found that 43 percent of the patients were B12 deficient and the remaining 48 patients had B12 levels on the low end of the normal spectrum.10
Clinicians have responded by recommending supplementation of all the B vitamins for their patients.
Magnesium has also been found to help sickle cell patients. Magnesium supplementation has been shown to reduce dense red blood cell clumping and improve the red blood cell membrane health. Magnesium supplementation should accompany healthy calcium levels.
Other deficiencies found in sickle cell children have included zinc and folic acid.
A 2000 study from the Philadelphia Biomedical Research Institute studied patients with sickle cell anemia13 and their heightened density and abnormal membranes of red blood cells. They experimented with some different nutritional supplements with the patients and in the laboratory. Compounds found to reduce dense cell formation included:
– aged garlic extract
– black tea extract
– green tea extract
– pine bark extract
– alpha-lipoic acid
– vitamin E
– Coenzyme Q(10)
They concluded that even a daily cocktail of aged garlic extract, vitamin C and vitamin E were beneficial for patients.
1. Wambebe C, Khamofu H, Momoh JA, Ekpeyong M, Audu BS, Njoku OS, Bamgboye EA, Nasipuri RN, Kunle OO, Okogun JI, Enwerem MN, Audam JG, Gamaniel KS, Obodozie OO, Samuel B, Fojule G, Ogunyale O. Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. Phytomedicine. 2001 Jul;8(4):252-61.
2. Wambebe CO, Bamgboye EA, Badru BO, Khamofu H, Momoh JA, Ekpeyong M, Audu BS, Njoku SO, Nasipuri NR, Kunle OO, Okogun JI, Enwerem NM, Gamaniel SK, Obodozie OO, Samuel B, Fojule G, Ogunyale PO. Efficacy of niprisan in the prophylactic management of patients with sickle cell disease. Curr Ther Res. 2001 Jan;62(1):26-34.
3. Adzu B, Masimirembwa C, Mustapha KB, Thelingwani R, Kirim RA, Gamaniel KS. Effect of NIPRISAN® on CYP3A4 activity in vitro. Eur J Drug Metab Pharmacokinet. 2015 Mar;40(1):115-8. doi: 10.1007/s13318-014-0173-1.
5. Ameh SJ, Tarfa FD, Ebeshi BU. Traditional herbal management of sickle cell anemia: lessons from Nigeria. Anemia. 2012;2012:607436. doi: 10.1155/2012/607436.
6. Akinsulie AO, Temiye EO, Akanmu AS, Lesi FE, Whyte CO. Clinical evaluation of extract of Cajanus cajan (Ciklavit) in sickle cell anaemia. J Trop Pediatr. 2005 Aug;51(4):200-5.
7. Moody JO, Segun FI, Aderounmu O, Omotade OO. ANTISICKLING ACTIVITY OF TERMINALIA CATAPPA LEAVES HARVESTED AT DIFFERENT STAGES OF GROWTH. Nigerian J Nat Prod Medicine. 2003;7
8. Moody JO, Ojo OO, Omotade OO, Adeyemo AA, Olumese PE, Ogundipe OO. Anti-sickling potential of a Nigerian herbal formula (ajawaron HF) and the major plant component (Cissus populnea L. CPK). Phytother Res. 2003 Dec;17(10):1173-6.
11. Perampaladas K, Masum H, Kapoor A, Shah R, Daar AS, Singer PA. The road to commercialization in Africa: lessons from developing the sickle-cell drug Niprisan. BMC Int Health Hum Rights. 2010 Dec 13;10 Suppl 1:S11.
12. Imaga NO, Gbenle GO, Okochi VI, et al. Antisickling property of Carica papaya leaf extract. African Journal of Biochemistry Research. 2009;3(4):102–106.
13. Ohnishi ST, Ohnishi T, Ogunmola GB. Sickle cell anemia: a potential nutritional approach for a molecular disease. Nutrition. 2000 May;16(5):330-8.
15. Ouattara B, Jansen O, Angenot L, Guissou IP, Frédérich M, Fondu P, Tits M. Antisickling properties of divanilloylquinic acids from Fagara zanthoxyloides Lam. (Rutaceae). Phytomedicine. 2009 Mar;16(2-3):125-9.
16. Obodozie OO, Ameh SJ, Afolabi EK, Oyedele EO, Ache TA, Onanuga CE, Ibe MC, Inyang US. A Normative Study of the Components of Niprisan-an Herbal Medicine for Sickle Cell Anemia. J Diet Suppl. 2010 Mar;7(1):21-30.
17. Ataga KI. Novel therapies in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2009:54-61.
18. Amoran OE, Jimoh AB, Ojo O, Kuponiyi T. Prevention practices influencing frequency of occurrence of vaso-occlusive crisis among sickle cell patients in Abeokuta South Local Government Area of Ogun State, Nigeria. BMC Hematol. 2017 Apr 20;17:6. doi: 10.1186/s12878-017-0077-9.
19. Tavs AA, Okpalaonyagu SO. Pharmacognostic evaluation and antisickling activity of the leaves of Peperomia pellucida (L.) HBK (Piperaceae). African Jour Pharma. 2015 June;9(21):561-566. DOI:10.5897/AJPP2015.
20. Ekpenyong, Ememobong & M, Okafor. (2018). Cocos Nucifera Water: Therapeutic Benefits and Sickle Cell Anemia Review. 8. 515-520.
21. Amujoyegbe OO, Idu M, Agbedahunsi JM, Erhabor JO. Ethnomedicinal survey of medicinal plants used in the management of sickle cell disorder in Southern Nigeria. J Ethnopharmacol. 2016 Jun 5;185:347-60. doi: 10.1016/j.jep.2016.03.042.